- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00978068
HIV Protease Inhibitors for the Prevention of Malaria in Ugandan Children (PROMOTE-PEDS)
A Randomized Open Label Trial of HIV Protease Inhibitors for the Prevention of Malaria in HIV-Infected Children
Descripción general del estudio
Estado
Condiciones
Descripción detallada
This is an open label, single site, randomized clinical trial comparing PI-based ART to NNRTI-based ART for the prevention of malaria in HIV-infected children. The two ART drug regimens that will be used include: Treatment arm 1. LPV/r + 2 NRTIs and Treatment arm 2. NVP or EFV + 2 NRTIs. The study is designed to test the hypothesis that children receiving a PI-based ART regimen will have lower the incidence of malaria compared to children receiving an NNRTI- based ART regimen. The primary study endpoint of the study is malaria incidence.
The study site will be the Tororo District Hospital campus situated in Eastern Uganda, an area of high malaria transmission. Using convenience sampling, 300 HIV-infected children identified from the Tororo community aged 2 months to <11 years either eligible for ART-initiation or already receiving a first line ART regimen with HIV RNA<400 copies/ml will be evaluated for enrollment.
Eligible children will be randomized at enrollment to receive either a PI- based or an NNRTI-based ART regimen. At enrollment, all study participants will receive a long lasting ITN as part of a basic care package including a safe water vessel and multivitamins and given TS chemoprophylaxis, as per current standard of care for HIV-infected children in Uganda. On the day of ART initiation, patients will be counseled about the importance of adherence to ART and possible ART related toxicities. After 2 weeks, patients will be seen to assess adherence and toxicity to study medications by interview and clinical examination. Apart from this visit at week 2, patients will be seen at 4 week intervals timed from ART-initiation. Assessment of adherence will also be done for TS prophylaxis, ITN use and ART. Assessment of adherence to ART will be done by self report of missed doses and pill counts.
Participants will receive all routine and acute medical care at a designated study clinic open 7 days a week from 8 a.m. to 5 p.m. Parents/guardians will be asked to bring their child to the study clinic for all medical care. If after hours, they will be instructed to bring them to Tororo District Hospital premises (where the study clinic is located) and request that the study physician on-call be contacted. They will be followed for at least 24 months and up to 3 years. They will be seen monthly for routine assessments with laboratory evaluations done at every 3 months. At these visits, the study protocol will be reinforced with discussion regarding the need to come to the study clinic promptly upon the onset of any illness and to avoid use of outside medications. Study participants will also be followed closely for adverse events potentially due to study drugs and for malaria and HIV treatment outcomes. During the follow-up period, all patients presenting to the clinic with a new episode of fever will undergo standard evaluation (history, physical examination) and Giemsa-stained blood smear for the diagnosis of malaria.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Tororo, Uganda
- IDRC - Tororo Research Clinic
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion criteria:
- Age 2 months to < 11 years
- Confirmed HIV diagnosis. i. Children > 18 months: Documentation of HIV status must come from two assays. Assays include DNA PCR, HIV RNA, Western blot, or rapid HIV antibody test ii. Children < 18 months: Documentation will be DNA PCR confirmation only along with documentation of testing from the referral entity
- ART-naïve patients eligible for ART initiation per WHO/Uganda guidelines (see Table 1) or Patients receiving first line ART regimen with NNRTI +2 NRTI with at least one HIV RNA <400 copies/ml within the past 6 months
- Agreement to come to the study clinic for any febrile episode or other illness
- Agreement to avoid medications administered outside study protocol
- Provision of informed consent by parent/guardian and agreement to have child's care at the clinical site
- Lives within 50 km of study site
Exclusion criteria:
- ART-naïve children: children or their mothers that have received any dose of Nevirapine in the past 24 months
- Active medical problem requiring in-patient evaluation at the time of screening or enrollment
- History of cardiac conduction disorder or known significant cardiac structural defect
- Children receiving any disallowed medications (see section 4.3)
Moderate, Severe or Life-threatening (Grade 2, 3, or 4) AST or ALT found within 4 weeks prior to enrollment:
- AST: >113U/L (>2.5xULN)
- ALT: >113U/L (>2.5xULN)
Life-threatening (Grade 4) screening laboratory value found within 4 weeks prior to enrollment for the following:
- Absolute neutrophil count: <500 mm3
- Hemoglobin: <6.5 g/dL
- Creatinine: >3.5xULN
- Platelets: <25,000/mm3
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador activo: Lopinavir/ritonavir (LPV/r) +2 NRTI
Lopinavir/ritonavir (LPV/r) +2 nucleoside reverse transcriptase inhibitor (NRTI)
|
Otros nombres:
The same NRTI choice strategy will be used for both arms.
Lamivudine will be used with all children.
The second NRTI will be zidovudine unless the participant has a hemoglobin < 8 gm/dL, in which case it will be Abacavir.
Stavudine will be used in the event that a participant is unable to take Abacavir for safety or other reasons.
|
Comparador activo: Nevirapine (NVP) or Efavirenz (EFV) +2 NRTI
Nevirapine (NVP) or Efavirenz (EFV) +2 nucleoside reverse transcriptase inhibitor (NRTI)
|
The same NRTI choice strategy will be used for both arms.
Lamivudine will be used with all children.
The second NRTI will be zidovudine unless the participant has a hemoglobin < 8 gm/dL, in which case it will be Abacavir.
Stavudine will be used in the event that a participant is unable to take Abacavir for safety or other reasons.
NVP will be used for children < 3 years of age
EFV for children ≥3 years of age
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Incidence-density of Malaria Defined as the Number of Incident Episodes of Malaria Per Time at Risk.
Periodo de tiempo: Time from randomization to at least 24 months of follow up or until end of the study
|
Time from randomization to at least 24 months of follow up or until end of the study
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Percentage of Uncomplicated Malaria Episodes With Accompanying Adverse Events That Occurred in the 28 Days Following Antimalarial Therapy
Periodo de tiempo: 28 days after antimalarial therapy
|
The rates of adverse events, defined as severity grade 2 or higher that are possibly, probably or definitely related to study drugs over the course of the 28-day period after antimalarial therapy with artemether-lumefantrine (AL).
|
28 days after antimalarial therapy
|
Incidence-density of Malaria Defined as the Number of Incident Episodes of Complicated Malaria Per Time at Risk.
Periodo de tiempo: Time from randomization to at least 24 months of follow up or until end of the study
|
Time from randomization to at least 24 months of follow up or until end of the study
|
|
Estimates of the 6-month Risk of a First Episode of Malaria
Periodo de tiempo: Enrollment to 6 months follow up
|
To assess the effect of ART independently of potential interactions with antimalarial therapy after treatment for malaria, we compared the two groups with respect to the time to the first episode of malaria.
Cumulative risk was estimated using the Kaplan-Meier product-limit formula.
|
Enrollment to 6 months follow up
|
28-day Risk of Recurrent Parasitemia
Periodo de tiempo: 28 days after antimalarial therapy
|
To assess the effect of potential interactions between ART and artemether-lumefantrine, the risks of recurrent parasitemia at 28 days were compared between the two groups.
|
28 days after antimalarial therapy
|
63-day Risk of Recurrent Malaria
Periodo de tiempo: 28 days after antimalarial therapy
|
To assess the effect of potential interactions between ART and artemether-lumefantrine, the risks of recurrent malaria at 63 days were compared between the two groups.
|
28 days after antimalarial therapy
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Grant Dorsey, MD, PhD, University of California, San Francisco
- Director de estudio: Diane V Havlir, MD, University of California, San Francisco
- Investigador principal: Moses R Kamya MBChB, MMed, MPH, Makerere University
- Investigador principal: Ted Ruel, MD, University of California, San Francisco
- Investigador principal: Jane Achan, MBChB, MPed, Makerere University
Publicaciones y enlaces útiles
Publicaciones Generales
- Achan J, Kakuru A, Ikilezi G, Ruel T, Clark TD, Nsanzabana C, Charlebois E, Aweeka F, Dorsey G, Rosenthal PJ, Havlir D, Kamya MR. Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children. N Engl J Med. 2012 Nov 29;367(22):2110-8. doi: 10.1056/NEJMoa1200501.
- Ikilezi G, Achan J, Kakuru A, Ruel T, Charlebois E, Clark TD, Rosenthal PJ, Havlir D, Kamya MR, Dorsey G. Prevalence of asymptomatic parasitemia and gametocytemia among HIV-infected Ugandan children randomized to receive different antiretroviral therapies. Am J Trop Med Hyg. 2013 Apr;88(4):744-6. doi: 10.4269/ajtmh.12-0658. Epub 2013 Jan 28.
- Nsanzabana C, Rosenthal PJ. In vitro activity of antiretroviral drugs against Plasmodium falciparum. Antimicrob Agents Chemother. 2011 Nov;55(11):5073-7. doi: 10.1128/AAC.05130-11. Epub 2011 Aug 29.
- Ruel TD, Kakuru A, Ikilezi G, Mwangwa F, Dorsey G, Rosenthal PJ, Charlebois E, Havlir D, Kamya M, Achan J. Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy. J Acquir Immune Defic Syndr. 2014 Apr 15;65(5):535-41. doi: 10.1097/QAI.0000000000000071.
- Kakuru A, Achan J, Muhindo MK, Ikilezi G, Arinaitwe E, Mwangwa F, Ruel T, Clark TD, Charlebois E, Rosenthal PJ, Havlir D, Kamya MR, Tappero JW, Dorsey G. Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children. Clin Infect Dis. 2014 Aug 1;59(3):446-53. doi: 10.1093/cid/ciu286. Epub 2014 Apr 23.
- Bartelink IH, Savic RM, Dorsey G, Ruel T, Gingrich D, Scherpbier HJ, Capparelli E, Jullien V, Young SL, Achan J, Plenty A, Charlebois E, Kamya M, Havlir D, Aweeka F. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda. Pediatr Infect Dis J. 2015 Mar;34(3):e63-70. doi: 10.1097/INF.0000000000000603.
- Achan J, Kakuru A, Ikilezi G, Mwangwa F, Plenty A, Charlebois E, Young S, Havlir D, Kamya M, Ruel T. Growth Recovery Among HIV-infected Children Randomized to Lopinavir/Ritonavir or NNRTI-based Antiretroviral Therapy. Pediatr Infect Dis J. 2016 Dec;35(12):1329-1332. doi: 10.1097/INF.0000000000001318.
- Bangirana P, Ruel TD, Boivin MJ, Pillai SK, Giron LB, Sikorskii A, Banik A, Achan J. Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy. J Int AIDS Soc. 2017 Oct;20(2):e25015. doi: 10.1002/jia2.25015.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones
- Enfermedades transmitidas por vectores
- Enfermedades parasitarias
- Infecciones por protozoos
- Malaria
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes Anti-VIH
- Agentes antirretrovirales
- Inhibidores de la proteasa
- Inhibidores del citocromo P-450 CYP3A
- Inhibidores de enzimas del citocromo P-450
- Inductores de enzimas de citocromo P-450
- Inductores de citocromo P-450 CYP3A
- Inhibidores de la proteasa del VIH
- Inhibidores de la proteasa viral
- Inductores de citocromo P-450 CYP2B6
- Inhibidores del citocromo P-450 CYP2C9
- Inhibidores del citocromo P-450 CYP2C19
- Nevirapina
- Ritonavir
- Lopinavir
- Inhibidores de la transcriptasa inversa
- Efavirenz
Otros números de identificación del estudio
- H5747-34097
- NIH PO1 HD059454
- 2009-114 (Otro identificador: Makerere Univ Fac of Med Research and Ethics Committee)
- HS-620 (Otro identificador: Uganda National Council for Science and Tech)
- 551/ESR/NDA/DID-08/09 (Otro identificador: Uganda National Drug Authority)
- H5741-34097 and 10-00991 (Otro identificador: UCSF Committee on Human Research)
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. .
Ensayos clínicos sobre Infecciones por VIH
-
Icahn School of Medicine at Mount SinaiIRRASReclutamientoHemorragia Intraventricular (HIV)Estados Unidos
-
Yale UniversityTerminadoPrecocidad | Recién nacidos de muy bajo peso al nacer | Hemorragia Intraventricular (HIV) | Sangrado en el cerebroEstados Unidos
-
China Medical University HospitalDesconocidoDisplasia broncopulmonar | Bebés extremadamente prematuros | TLP grave que las terapias convencionales han fallado | Sin anomalías congénitas graves | no Hiv Severa Ni FPV QuísticaTaiwán
Ensayos clínicos sobre Lopinavir/Ritonavir (LPV/r)
-
University of LiverpoolJanssen Pharmaceutica; Yaounde Central Hospital; Chantal Biya International Reference...Terminado
-
University of California, San DiegoAbbottTerminadoInfección por VIHEstados Unidos
-
National Institute of Allergy and Infectious Diseases...TerminadoVIHEstados Unidos, Sudáfrica, Tailandia, Brasil
-
Emory UniversityAbbottTerminadoInfecciones por VIHEstados Unidos
-
The HIV Netherlands Australia Thailand Research...National Health Security Office, Thailand; Swiss HIV Cohort StudyTerminado
-
Peking Union Medical CollegeDesconocidoEL PROBLEMA DEL SIDA/VIHPorcelana
-
AbbottMerck Sharp & Dohme LLCTerminadoInfección por el virus de la inmunodeficiencia humanaEstados Unidos, Canadá, Francia, Italia, Polonia, Puerto Rico, España
-
French National Agency for Research on AIDS and...Merck Sharp & Dohme LLCTerminado
-
AbbottTerminadoInfecciones por el virus de la inmunodeficiencia humanaEstados Unidos, Australia, Bélgica, Canadá, República Checa, Francia, Alemania, Grecia, Irlanda, Italia, Países Bajos, Polonia, Puerto Rico, Federación Rusa, Singapur, España, Suiza, Taiwán, Reino Unido
-
AbbottTerminadoInfecciones por el virus de la inmunodeficiencia humanaEstados Unidos