Evaluación de la exposición-respuesta al artesunato intravenoso en niños con paludismo grave
21 de mayo de 2026 actualizado por: National Institute of Allergy and Infectious Diseases (NIAID)
En este estudio, los niños ugandeses a los que se les diagnostica paludismo grave recibirán artesunato por vía intravenosa (IV) según las directrices de la Organización Mundial de la Salud (OMS).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
A pesar de los avances recientes en el control de la malaria, el Plasmodium falciparum sigue matando a casi medio millón de personas al año, la mayoría de las cuales son niños que viven en el África subsahariana. Plasmodium falciparum es la especie de parásito de la malaria más prevalente y la causa de la forma más grave de enfermedad y muerte. Representó el 99,7% de todos los casos de malaria en la Región de África de la Organización Mundial de la Salud (OMS) en 2018. Los niños menores de 5 años y las mujeres embarazadas corren mayor riesgo de malaria y muerte, y representan el 67 % de las 405 000 muertes por malaria estimadas en todo el mundo, con el 94 % de estas en la Región de África. Aunque hubo una reducción general en las muertes por malaria en 2018 en comparación con 2010, la tasa de reducción de la mortalidad por malaria se desaceleró desde 2016 y esto hace que los investigadores de malaria se pregunten si los regímenes actuales de tratamiento de malaria son óptimos y se basan en evidencia científica sólida.
La malaria grave es una emergencia médica que, si no se trata de inmediato, provoca una mortalidad del 100 %. Es fundamental que las concentraciones plasmáticas de un fármaco antipalúdico altamente eficaz se alcancen lo más rápido posible. El artesunato es un derivado de la artemisinina hemisuccinato soluble en agua, disponible como sal de hemisuccinato de sodio para inyección. La excelente propiedad antipalúdica del artesunato demostrada por la eliminación rápida de parásitos se ve reforzada por su alta concentración máxima inicial (Cmax) y su rápida hidrólisis a su metabolito activo dihidroartemisinina (DHA).
Los regímenes de dosificación actuales para el artesunato IV se basan en el tiempo hasta la eliminación del parásito y no en criterios de valoración clínicos relacionados con los cambios fisiológicos que ocurren con la parasitemia. Se pueden utilizar otras medidas de disfunción fisiológica como criterios de valoración del estudio para un análisis de los resultados del tratamiento de la malaria de los regímenes actuales de artesunato IV para el tratamiento de la malaria grave. Los regímenes de dosificación mejorados conducirán a menos complicaciones y probablemente a menos muertes. Se necesita una estrategia de este tipo para reducir aún más los beneficios de la salud pública contra la mortalidad por malaria que parecen haberse estancado recientemente.
Para los pacientes pediátricos, la dosificación de artesunato IV se basa en el peso para ajustar la depuración de artesunato y se ha desarrollado en función del tiempo de depuración de la parasitemia, que puede no reflejar completamente la curación clínica. Los parásitos P. falciparum son conocidos por su capacidad para infectar glóbulos rojos que luego muestran antígenos de superficie variantes que se adhieren a la vasculatura endotelial en los órganos diana. Por esta razón, la medición de la eliminación de parásitos en la sangre periférica puede no reflejar los efectos fisiológicos de la malaria grave que resultan del daño de los órganos diana, ya sea a través del deterioro directo del flujo sanguíneo y la disminución del suministro de oxígeno, una respuesta inflamatoria local dirigida contra los glóbulos rojos infectados. unido al endotelio vascular, o formación de rosetas de glóbulos rojos infectados y no infectados en la vasculatura. Otras medidas de disfunción fisiológica, cuando se cuantifican solas o de forma algorítmica, como una puntuación, pueden reflejar con mayor precisión el tratamiento exitoso, incluido el lactato sérico, la glucosa sérica, los niveles de bicarbonato, BCS, creatinina y hemoglobina. Estas medidas, en comparación con los tiempos estándar de eliminación de parásitos de la sangre periférica, pueden ser más importantes para cuantificar y relacionar la dosificación farmacológica de la terapia antipalúdica.
Este estudio tiene como objetivo desarrollar un régimen mejorado de dosificación de artesunato IV para el tratamiento de la malaria grave en niños.
Tipo de estudio
Intervencionista
Inscripción (Actual)
90
Fase
- Fase 4
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Kampala, Uganda
- Makerere University-Infectious Diseases Institute
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
6 meses a 14 años (Niño)
Acepta Voluntarios Saludables
No
Población de estudio
Este estudio está reclutando a niños ugandeses de 6 meses a 14 años de edad que han sido diagnosticados con malaria grave de acuerdo con los criterios estandarizados de la Organización Mundial de la Salud (OMS) (cualquier parasitemia por P. falciparum y presencia de signos de peligro).
Descripción
Criterios de inclusión:
- Niños de 6 meses a 14 años en el momento del diagnóstico de malaria grave, inclusive
- Cumplir con la definición de caso de paludismo grave, según las directrices estandarizadas de la OMS
- Padre/tutor dispuesto a dar su consentimiento informado
- Asentimiento para niños entre 8 y 14 años que estén conscientes y que de otro modo puedan dar su asentimiento, inclusive
- Vivir en o cerca del distrito de Tororo, Uganda
Criterio de exclusión:
- Recepción de >24 horas de terapia con artemisinina
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Brazo 1
Los participantes recibirán el estándar de atención con artesunato intravenoso para el tratamiento de la malaria grave.
Cada vial de 60 mg de ácido artesunico se disolverá en 1 ml de bicarbonato de sodio al 5 % para formar artesunato de sodio y luego se mezclará con 5 ml de dextrosa al 5 %.
Esto se inyectará en forma de bolo en una cánula intravenosa permanente.
Los niños que pesen <20 kg recibirán artesunato intravenoso en una dosis de 3,0 mg/kg/dosis en comparación con los niños mayores que pesen >/= 20 kg que recibirán 2,4 mg/kg/dosis, en los momentos 0, 12, 24.
Si no puede tomar la medicación oral, se continuará con artesunato intravenoso a las 48 y 72 horas.
Los niños que se recuperen y puedan hacer la transición a la terapia antipalúdica oral después de un mínimo de 24 horas iniciarán un ciclo de 3 días de terapia combinada de artemisinina oral según las pautas nacionales.
norte = 100
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El artesunato es un éster succínico del arteméter.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Maximum Concentration (Cmax) of Dihydroartemisinin (DHA)
Periodo de tiempo: Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Population Pharmacokinetic (PK) modeling was conducted to derive Cmax from the concentration of DHA.
The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.
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Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Area Under the Curve Over 0-12 Hours (AUC0-12) of DHA
Periodo de tiempo: Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Population PK modeling was conducted to derive AUC0-12 from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin. Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate) |
Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Half-life (t1/2) of DHA
Periodo de tiempo: Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Population PK modeling was conducted to derive t1/2 from the concentration of DHA.
The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.
|
Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Time to Cmax (Tmax) of DHA
Periodo de tiempo: Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Population Pharmacokinetic (PK) modeling was conducted to derive PK parameters from the concentration of DHA.
The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.
From the simulation, the Tmax was assumed to be 0 as the simulation replicates artesunate administered as an IV bolus directly into the central compartment.
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Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
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Change From Baseline in Temperature in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits.
Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK Parameters (AUC0-12, Cmax, and t1/2) and temperature.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Temperature in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits.
Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and temperature.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline Systolic Blood Pressure (BP) in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits.
Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP.
Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline Systolic BP in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits.
Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP.
Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline Diastolic BP in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits.
Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and diastolic BP.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline Diastolic BP in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits.
Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and diastolic BP.
Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From in Venous Serum Lactate in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum lactate was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From in Venous Serum Lactate in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum lactate was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Serum Bicarbonate in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Serum Bicarbonate in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Serum Glucose in the Primary Analysis Population
Periodo de tiempo: 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum glucose was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.
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24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Serum Glucose in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum glucose was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Total Bilirubin in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Total bilirubin was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Total Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Total bilirubin was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Direct Bilirubin in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Direct bilirubin was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in direct bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and direct bilirubin.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for direct bilirubin.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Direct Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Direct bilirubin was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in direct bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and direct bilirubin.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for direct bilirubin.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
Change From Baseline in Hemoglobin in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Hemoglobin was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in hemoglobin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and hemoglobin.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for hemoglobin.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
|
Change From Baseline in Hemoglobin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Hemoglobin was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in hemoglobin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and hemoglobin.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for hemoglobin.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Creatinine in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Creatinine was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in creatinine was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and creatinine.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for creatinine.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
Change From Baseline in Creatinine in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Creatinine was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in creatinine was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and creatinine.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for creatinine.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA AUC0-12 Summary Statistics for Participants With Blantyre Coma Score (BCS) of 1 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA AUC0-12 for BCS score of 1 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA AUC0-12 Summary Statistics for Participants With BCS of 4 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA AUC0-12 for BCS score of 4 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA AUC0-12 Summary Statistics for Participants With BCS of 5 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA AUC0-12 for BCS score of 5 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA AUC0-12 Summary Statistics for Participants With BCS of 4 in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
BCS is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA AUC0-12 for BCS score of 4 by timepoint are presented.
Only participants who were assessed a BCS of 4 are shown.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
DHA AUC0-12 Summary Statistics for Participants With BCS of 5 in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA AUC0-12 for BCS score of 5 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA Cmax Summary Statistics for Participants With BCS of 1 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA Cmax for BCS score of 1 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA Cmax Summary Statistics for Participants With BCS of 4 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA Cmax for BCS score of 4 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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DHA Cmax Summary Statistics for Participants With BCS of 5 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA Cmax for BCS score of 5 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
DHA Cmax Summary Statistics for Participants With BCS of 4 in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA Cmax for BCS score of 4 by timepoint are presented.
Only participants who were assessed a BCS of 4 are shown.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
DHA Cmax Summary Statistics for Participants With BCS of 5 in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA Cmax for BCS score of 5 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
DHA t1/2 Summary Statistics for Participants With BCS of 1 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA t1/2 for BCS score of 1 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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|
DHA t1/2 Summary Statistics for Participants With BCS of 4 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA t1/2 for BCS score of 4 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
|
DHA t1/2 Summary Statistics for Participants With BCS of 5 in the Primary Analysis Population
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA t1/2 for BCS score of 5 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
|
DHA t1/2 Summary Statistics for Participants With BCS of 4 in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA t1/2 for BCS score of 4 by timepoint are presented.
Only participants who were assessed a BCS of 4 are shown.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
|
DHA t1/2 Summary Statistics for Participants With BCS of 5 in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Blantyre coma scale is an ordinal scale designed to assess malarial coma in children.
Eye movement, best motor response, and best verbal response were assessed and scored.
The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness.
BCS was recorded daily until discharge along with scheduled follow-up visits.
The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted.
Instead, summary statistics of DHA t1/2 for BCS score of 5 by timepoint are presented.
|
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Time to Hospital Discharge in the Primary Analysis Population
Periodo de tiempo: Day 1 through Day 9
|
Dates and times of hospital admittance and discharge for each participant were collected for calculation of time to hospital discharge.
Time to hospital discharge was defined as the time in days from initial participant admission to the time of first discharge.
Time to hospital discharge was calculated using the actual dates and times of initial participant admission and first discharge and was rounded to the nearest tenths place.
|
Day 1 through Day 9
|
|
Time to Hospital Discharge in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Day 1 through Day 9
|
Dates and times of hospital admittance and discharge for each participant were collected for calculation of time to hospital discharge.
Time to hospital discharge was defined as the time in days from initial participant admission to the time of first discharge.
Time to hospital discharge was calculated using the actual dates and times of initial participant admission and first discharge and was rounded to the nearest tenths place.
|
Day 1 through Day 9
|
|
Parasite (Plasmodium Falciparum) Density in Thick Blood Smear in the Primary Analysis Population
Periodo de tiempo: Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
Parasite clearance as calculated from parasite density over time, as measured by thick blood smear.
Parasite density is defined as the number of parasites per 200 white blood cells (WBCs).
Parasite clearance half-life (PCT50) and parasite clearance time to 90% reduction (PCT90) were estimated using the WorldWide Antimalarial Resistance Network (WWARN) parasite clearance estimator (PCE) algorithm.
|
Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
|
Parasite (P. Falciparum) Density in Thick Blood Smear in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
Parasite clearance as calculated from parasite density over time, as measured by thick blood smear.
Parasite density is defined as the number of parasites per 200 white blood cells (WBCs).
Parasite clearance half-life (PCT50) and parasite clearance time to 90% reduction (PCT90) were estimated using the WorldWide Antimalarial Resistance Network (WWARN) parasite clearance estimator (PCE) algorithm.
|
Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
|
Number of Participants With Parasite (P. Falciparum) Clearance in the Primary Analysis Population
Periodo de tiempo: Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
Total parasite clearance was defined as the first negative thick blood smear (i.e., a thick blood smear for which there were no detectable P. falciparum parasites per 200 WBC) after a participant's last positive blood smear for P. falciparum.
The date and time of total parasite clearance was defined as the collection date and time of the first thick blood smear to meet the definition of parasite clearance.
Total parasite clearance by Day 2 was defined as a binary variable indicating whether total parasite clearance occurred within the first 50 hours post-first on-study dose of IV artesunate.
|
Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
|
Number of Participants With Parasite (P. Falciparum) Clearance in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Periodo de tiempo: Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
Total parasite clearance was defined as the first negative thick blood smear (i.e., a thick blood smear for which there were no detectable P. falciparum parasites per 200 WBC) after a participant's last positive blood smear for P. falciparum.
The date and time of total parasite clearance was defined as the collection date and time of the first thick blood smear to meet the definition of parasite clearance.
Total parasite clearance by Day 2 was defined as a binary variable indicating whether total parasite clearance occurred within the first 50 hours post-first on-study dose of IV artesunate.
|
Day 1 through Day 7 (Samples were collected according to the following schedule post-first on-study dose of IV artesunate in hours: 0, 6, 12, 24, 36, and 48 hours, and at least every 24 hours until clearance.)
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Investigadores
- Investigador principal: Matthew B Laurens, MD, MPH, University of Maryland School of Medicine
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
29 de noviembre de 2023
Finalización primaria (Actual)
1 de abril de 2025
Finalización del estudio (Actual)
1 de abril de 2025
Fechas de registro del estudio
Enviado por primera vez
20 de febrero de 2023
Primero enviado que cumplió con los criterios de control de calidad
20 de febrero de 2023
Publicado por primera vez (Actual)
1 de marzo de 2023
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
18 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
21 de mayo de 2026
Última verificación
9 de octubre de 2025
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades transmitidas por vectores
- Enfermedades transmitidas por mosquitos
- Infecciones
- Infecciones por protozoos
- Enfermedades parasitarias
- Malaria
- Químicos orgánicos
- Hidrocarburos
- Terpenos
- Químicos inorgánicos
- Especies reactivas de oxígeno
- Radicales libres
- Artemisininas
- Sesquiterpenos
- Artesunato
Otros números de identificación del estudio
- 19-0007
- 5UM1AI148689-03 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
Descripción del plan IPD
Los datos de participantes individuales no identificados relacionados con el análisis primario estarán disponibles para compartir con otros investigadores.
Marco de tiempo para compartir IPD
Los datos estarán disponibles para compartirlos tras la publicación de los resultados del estudio principal, sin fecha de finalización.
Criterios de acceso compartido de IPD
Los datos estarán disponibles en una base de datos accesible, en una plataforma en línea.
Los investigadores podrán acceder a los datos para realizar análisis relacionados con los objetivos de estudio propuestos.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
Sí
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .