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Eksponering-responsevaluering av IV Artesunate hos barn med alvorlig malaria

21. mai 2026 oppdatert av: National Institute of Allergy and Infectious Diseases (NIAID)
I denne studien vil ugandiske barn som er diagnostisert med alvorlig malaria få intravenøs (IV) artesunat i henhold til retningslinjer fra Verdens helseorganisasjon (WHO).

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Til tross for nylige fremskritt innen malariakontroll, fortsetter Plasmodium falciparum å drepe nesten en halv million mennesker årlig, hvorav de fleste er barn som bor i Afrika sør for Sahara. Plasmodium falciparum er den mest utbredte malariaparasittarten og årsaken til den alvorligste formen for sykdom og død. Det utgjorde 99,7 % av alle malariatilfeller i Verdens helseorganisasjon (WHO) Afrikaregion i 2018. Barn yngre enn 5 år og gravide kvinner er mest utsatt for malaria og død, og står for 67 % av de estimerte 405 000 malariadødsfallene på verdensbasis, med 94 % av disse i den afrikanske regionen. Selv om det var en generell reduksjon i malariadødsfall i 2018 sammenlignet med 2010, har reduksjonsraten for malariadødelighet avtatt siden 2016, og dette har fått malariaforskere til å stille spørsmål ved om dagens malariabehandlingsregimer er optimale og basert på solid vitenskapelig bevis.

Alvorlig malaria er en medisinsk nødsituasjon som hvis den ikke behandles umiddelbart resulterer i 100 % dødelighet. Det er grunnleggende at plasmakonsentrasjoner av et svært effektivt antimalariamiddel oppnås så raskt som mulig. Artesunate er et vannløselig hemisuccinat artemisinin-derivat, tilgjengelig som natriumhemisuccinatsalt for injeksjon. Artesunates utmerkede antimalaria-egenskap demonstrert ved rask parasitt-clearance, forsterkes av dens høye initiale maksimale konsentrasjon (Cmax) og raske hydrolyse til dens aktive metabolitt dihydroartemisinin (DHA).

Gjeldende doseringsregimer for IV artesunat er basert på tid til parasittclearance og ikke kliniske endepunkter relatert til fysiologiske endringer som oppstår med parasitemi. Andre mål på fysiologisk dysfunksjon kan brukes som studieendepunkter for en malariabehandlingsresultatanalyse av gjeldende regimer for IV artesunat for alvorlig malariabehandling. Forbedrede doseringsregimer vil føre til færre komplikasjoner og sannsynligvis færre dødsfall. En slik strategi er nødvendig for ytterligere å redusere folkehelsegevinster mot malariadødelighet som nylig ser ut til å ha stoppet opp.

For pediatriske pasienter er IV artesunat-dosering vektbasert for å justere for artesunat-clearance og er utviklet basert på tid til parasitemi-clearance-tider, som kanskje ikke helt gjenspeiler klinisk kur. P. falciparum-parasitter er kjent for sin evne til å infisere røde blodceller som deretter viser varianter av overflateantigener som fester seg til endotelvaskulatur i målorganer. Av denne grunn kan det hende at måling av parasittclearance i det perifere blodet ikke reflekterer fysiologiske effekter av alvorlig malaria som skyldes endeorganskade, enten det er gjennom direkte svekkelse av blodstrømmen og redusert tilførsel av oksygen, en lokal inflammatorisk respons rettet mot infiserte røde blodlegemer. festet til vaskulært endotel, eller rosett av infiserte og uinfiserte røde blodlegemer ved vaskulaturen. Andre mål på fysiologisk dysfunksjon når de kvantifiseres alene eller på en algoritmisk måte som en skåre, kan mer nøyaktig reflektere vellykket behandling, inkludert serumlaktat, serumglukose, bikarbonatnivåer, BCS, kreatinin og hemoglobin. Disse målene, sammenlignet med standard parasitt-clearance-tider fra perifert blod, kan være viktigere å kvantifisere og relatere til farmakologisk dosering av antimalariabehandling.

Denne studien tar sikte på å utvikle et forbedret IV artesunat doseringsregime for behandling av alvorlig malaria hos barn.

Studietype

Intervensjonell

Registrering (Faktiske)

90

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Uganda
      • Kampala, Uganda
        • Makerere University-Infectious Diseases Institute

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

6 måneder til 14 år (Barn)

Tar imot friske frivillige

Nei

Studiepopulasjon

Denne studien registrerer ugandiske barn fra 6 måneder til 14 år som er diagnostisert med alvorlig malaria i henhold til standardiserte kriterier fra Verdens helseorganisasjon (WHO) (enhver P. falciparum parasitemia og tilstedeværelsen av faretegn).

Beskrivelse

Inklusjonskriterier:

  • Barn i alderen 6 måneder til 14 år på tidspunktet for alvorlig malariadiagnose, inkludert
  • Oppfyll saksdefinisjonen for alvorlig malaria, i henhold til WHOs standardiserte retningslinjer
  • Foreldre/foresatte villig til å gi informert samtykke
  • Samtykke for barn mellom 8 og 14 år som er ved bevissthet og ellers i stand til å gi samtykke, inklusive
  • Bor i eller i nærheten av Tororo District, Uganda

Ekskluderingskriterier:

  • Mottak av >24 timers artemisininbehandling

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Arm 1
Deltakerne vil motta standardbehandling med IV artesunate for behandling av alvorlig malaria. Hvert 60-mg hetteglass med artesunsyre vil bli oppløst i 1 ml 5 % natriumbikarbonat for å danne natriumartesunat og deretter blandes med 5 ml 5 % dekstrose. Dette vil bli injisert som en bolus i en inneliggende IV-kanyle. Barn som veier <20 kg vil få IV artesunat i en dose på 3,0 mg/kg/dose sammenlignet med eldre barn som veier >/= 20 kg som vil få 2,4 mg/kg/dose, til tidene 0, 12, 24. Hvis du ikke kan ta orale medisiner, vil IV artesunate fortsette etter 48 og 72 timer. Barn som blir friske og kan gå over til oral antimalariabehandling etter minimum 24 timer, vil starte en 3-dagers kur med oral artemisinin-kombinasjonsbehandling i henhold til nasjonale retningslinjer. N = 100
Legemiddel: Artesunate
Artesunate er en succinisk ester av artemether.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Maximum Concentration (Cmax) of Dihydroartemisinin (DHA)
Tidsramme: 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)
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.
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)
Area Under the Curve Over 0-12 Hours (AUC0-12) of DHA
Tidsramme: 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)

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)
Half-life (t1/2) of DHA
Tidsramme: 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)
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)
Time to Cmax (Tmax) of DHA
Tidsramme: 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)
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.
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)
Change From Baseline in Temperature in the Primary Analysis Population
Tidsramme: 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)
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.
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 Temperature in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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.
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 Systolic Blood Pressure (BP) in the Primary Analysis Population
Tidsramme: 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)
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.
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 Systolic BP in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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.
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 Diastolic BP in the Primary Analysis Population
Tidsramme: 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)
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.
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 Diastolic BP in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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.
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 in Venous Serum Lactate in the Primary Analysis Population
Tidsramme: 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)
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.
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 in Venous Serum Lactate in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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.
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 Serum Bicarbonate in the Primary Analysis Population
Tidsramme: 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)
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.
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 Serum Bicarbonate in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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.
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 Serum Glucose in the Primary Analysis Population
Tidsramme: 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)
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.
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 Serum Glucose in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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.
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 Total Bilirubin in the Primary Analysis Population
Tidsramme: 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)
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)
Change From Baseline in Total Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
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)
Change From Baseline in Direct Bilirubin in the Primary Analysis Population
Tidsramme: 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)
Change From Baseline in Direct Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
Change From Baseline in Hemoglobin in the Primary Analysis Population
Tidsramme: 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
Tidsramme: 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 Creatinine in the Primary Analysis Population
Tidsramme: 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)
Change From Baseline in Creatinine in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Tidsramme: 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)
DHA AUC0-12 Summary Statistics for Participants With Blantyre Coma Score (BCS) of 1 in the Primary Analysis Population
Tidsramme: 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)
DHA AUC0-12 Summary Statistics for Participants With BCS of 4 in the Primary Analysis Population
Tidsramme: 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)
DHA AUC0-12 Summary Statistics for Participants With BCS of 5 in the Primary Analysis Population
Tidsramme: 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)
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
Tidsramme: 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)
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
Tidsramme: 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)
DHA Cmax Summary Statistics for Participants With BCS of 1 in the Primary Analysis Population
Tidsramme: 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)
DHA Cmax Summary Statistics for Participants With BCS of 4 in the Primary Analysis Population
Tidsramme: 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)
DHA Cmax Summary Statistics for Participants With BCS of 5 in the Primary Analysis Population
Tidsramme: 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)
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
Tidsramme: 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)
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
Tidsramme: 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)
DHA t1/2 Summary Statistics for Participants With BCS of 1 in the Primary Analysis Population
Tidsramme: 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)
DHA t1/2 Summary Statistics for Participants With BCS of 4 in the Primary Analysis Population
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Time to Hospital Discharge in the Primary Analysis Population
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbeidspartnere

University of Maryland, Baltimore
Makerere University

Etterforskere

  • Hovedetterforsker: Matthew B Laurens, MD, MPH, University of Maryland School of Medicine

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

29. november 2023

Primær fullføring (Faktiske)

1. april 2025

Studiet fullført (Faktiske)

1. april 2025

Datoer for studieregistrering

Først innsendt

20. februar 2023

Først innsendt som oppfylte QC-kriteriene

20. februar 2023

Først lagt ut (Faktiske)

1. mars 2023

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

18. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. mai 2026

Sist bekreftet

9. oktober 2025

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 19-0007
  • 5UM1AI148689-03 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

IPD-planbeskrivelse

Avidentifiserte individuelle deltakerdata knyttet til primæranalysen vil bli gjort tilgjengelig for deling med andre forskere.

IPD-delingstidsramme

Data vil bli gjort tilgjengelig for deling ved publisering av primære studieresultater, uten sluttdato.

Tilgangskriterier for IPD-deling

Data vil bli gjort tilgjengelig i en tilgjengelig database, i en nettplattform. Forskere vil kunne få tilgang til dataene for analyser relatert til deres foreslåtte studiemål.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Ja

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere