Ocena ekspozycji i odpowiedzi na artesunate IV u dzieci z ciężką malarią
21 maja 2026 zaktualizowane przez: National Institute of Allergy and Infectious Diseases (NIAID)
W tym badaniu ugandyjskie dzieci, u których zdiagnozowano ciężką malarię, otrzymają dożylnie (IV) artesunat zgodnie z wytycznymi Światowej Organizacji Zdrowia (WHO).
Przegląd badań
Szczegółowy opis
Pomimo niedawnych postępów w zwalczaniu malarii Plasmodium falciparum nadal zabija prawie pół miliona osób rocznie, z których większość to dzieci mieszkające w Afryce Subsaharyjskiej. Plasmodium falciparum jest najbardziej rozpowszechnionym gatunkiem pasożyta malarii i przyczyną najcięższej postaci choroby i śmierci. Stanowiło to 99,7% wszystkich przypadków malarii w regionie afrykańskim Światowej Organizacji Zdrowia (WHO) w 2018 roku. Dzieci w wieku poniżej 5 lat i kobiety w ciąży są najbardziej narażone na malarię i śmierć, co odpowiada za 67% z szacowanych 405 000 zgonów z powodu malarii na całym świecie, z czego 94% w regionie afrykańskim. Chociaż w 2018 r. nastąpił ogólny spadek liczby zgonów z powodu malarii w porównaniu z 2010 r., wskaźnik redukcji śmiertelności z powodu malarii zwolnił od 2016 r., co powoduje, że badacze zajmujący się malarią kwestionują, czy obecne schematy leczenia malarii są optymalne i oparte na solidnych dowodach naukowych.
Ciężka malaria to nagły przypadek medyczny, który, jeśli nie zostanie natychmiast leczony, powoduje 100% śmiertelność. Zasadnicze znaczenie ma jak najszybsze osiągnięcie stężenia w osoczu wysoce skutecznego leku przeciwmalarycznego. Artesunat jest rozpuszczalną w wodzie hemibursztynianem, pochodną artemizyniny, dostępną w postaci hemibursztynianu sodu do wstrzykiwań. Doskonałe właściwości przeciwmalaryczne artesunatu, wykazywane przez szybkie eliminowanie pasożytów, są wzmocnione przez jego wysokie początkowe maksymalne stężenie (Cmax) i szybką hydrolizę do aktywnego metabolitu dihydroartemizyniny (DHA).
Obecne schematy dawkowania artesunatu podawanego dożylnie opierają się na czasie do usunięcia pasożyta, a nie na klinicznych punktach końcowych związanych ze zmianami fizjologicznymi występującymi w przypadku parazytemii. Inne miary dysfunkcji fizjologicznych można wykorzystać jako punkty końcowe badania do analizy wyników leczenia malarii obecnych schematów podawania artesunatu dożylnie w leczeniu ciężkiej malarii. Ulepszone schematy dawkowania doprowadzą do mniejszej liczby powikłań i prawdopodobnie mniejszej liczby zgonów. Taka strategia jest potrzebna, aby jeszcze bardziej ograniczyć korzyści w zakresie zdrowia publicznego związane ze śmiertelnością z powodu malarii, która wydaje się ostatnio utknąć w martwym punkcie.
W przypadku pacjentów pediatrycznych dawkowanie artesunatu dożylnie jest uzależnione od masy ciała w celu dostosowania do klirensu artesunatu i zostało opracowane w oparciu o czasy ustąpienia parazytemii, które mogą nie odzwierciedlać w pełni wyleczenia klinicznego. Pasożyty P. falciparum są znane ze swojej zdolności do infekowania krwinek czerwonych, które następnie prezentują różne antygeny powierzchniowe, które przylegają do naczyń śródbłonka w narządach docelowych. Z tego powodu pomiar klirensu pasożytów we krwi obwodowej może nie odzwierciedlać fizjologicznych skutków ciężkiej malarii, które wynikają z uszkodzenia narządów końcowych, czy to poprzez bezpośrednie upośledzenie przepływu krwi i zmniejszenie dostarczania tlenu, lokalną reakcję zapalną skierowaną przeciwko zakażonym krwinkom czerwonym przyczepione do śródbłonka naczyniowego lub rozetki zakażonych i niezainfekowanych krwinek czerwonych w układzie naczyniowym. Inne miary dysfunkcji fizjologicznych, gdy są określane ilościowo samodzielnie lub w sposób algorytmiczny, takie jak punktacja, mogą dokładniej odzwierciedlać skuteczne leczenie, w tym mleczanów w surowicy, glukozy w surowicy, poziomów wodorowęglanów, BCS, kreatyniny i hemoglobiny. Miary te, w porównaniu ze standardowymi czasami usuwania pasożytów z krwi obwodowej, mogą być ważniejsze do ilościowego określenia i odnoszą się do farmakologicznego dawkowania terapii przeciwmalarycznej.
Niniejsze badanie ma na celu opracowanie udoskonalonego schematu dawkowania artesunatu dożylnego w leczeniu ciężkiej postaci malarii u dzieci.
Typ studiów
Interwencyjne
Zapisy (Rzeczywisty)
90
Faza
- Faza 4
Kontakty i lokalizacje
Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.
Lokalizacje studiów
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Kampala, Uganda
- Makerere University-Infectious Diseases Institute
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Kryteria uczestnictwa
Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.
Kryteria kwalifikacji
Wiek uprawniający do nauki
6 miesięcy do 14 lat (Dziecko)
Akceptuje zdrowych ochotników
Nie
Badana populacja
Do tego badania włączono ugandyjskie dzieci w wieku od 6 miesięcy do 14 lat, u których zdiagnozowano ciężką malarię zgodnie ze standardowymi kryteriami Światowej Organizacji Zdrowia (WHO) (jakakolwiek parazytemia P. falciparum i obecność oznak zagrożenia).
Opis
Kryteria przyjęcia:
- Dzieci w wieku od 6 miesięcy do 14 lat w momencie rozpoznania ciężkiej malarii włącznie
- Spełnij definicję przypadku ciężkiej malarii, zgodnie ze standardowymi wytycznymi WHO
- Rodzic/opiekun chętny do wyrażenia świadomej zgody
- Zgoda dla dzieci w wieku od 8 do 14 lat, które są przytomne iw inny sposób zdolne do wyrażenia zgody włącznie
- Mieszka w dystrykcie Tororo lub w jego pobliżu w Ugandzie
Kryteria wyłączenia:
- Odbiór >24 godzin terapii artemizyniną
Plan studiów
Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nie dotyczy
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: Ramię 1
Uczestnicy otrzymają standardową opiekę z artesunatem dożylnym w leczeniu ciężkiej malarii.
Każda fiolka 60 mg kwasu artesunowego zostanie rozpuszczona w 1 ml 5% wodorowęglanu sodu, tworząc artesunian sodu, a następnie zmieszana z 5 ml 5% dekstrozy.
Zostanie on wstrzyknięty w postaci bolusa do założonej na stałe kaniuli dożylnej.
Dzieci o masie ciała <20 kg będą otrzymywać artesunat dożylnie w dawce 3,0 mg/kg/dawkę w porównaniu do starszych dzieci o masie ciała >/= 20 kg, które otrzymają 2,4 mg/kg/dawkę, w czasach 0, 12, 24.
Jeżeli nie można przyjmować leków doustnych, podawanie artesunatu dożylnego będzie kontynuowane po 48 i 72 godzinach.
Dzieci, które wyzdrowieją i będą mogły przejść na doustną terapię przeciwmalaryczną po co najmniej 24 godzinach, rozpoczną 3-dniowy cykl doustnej terapii skojarzonej z artemizyną, zgodnie z krajowymi wytycznymi.
N = 100
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Artesunate to ester bursztynowy artemeteru.
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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Maximum Concentration (Cmax) of Dihydroartemisinin (DHA)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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.
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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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Time to Cmax (Tmax) of DHA
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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.
|
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
Ramy czasowe: 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 Total Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Ramy czasowe: 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
Ramy czasowe: 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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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
Ramy czasowe: 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
Ramy czasowe: 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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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.
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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 Hemoglobin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Ramy czasowe: 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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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
Ramy czasowe: 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
Ramy czasowe: 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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DHA AUC0-12 Summary Statistics for Participants With Blantyre Coma Score (BCS) of 1 in the Primary Analysis Population
Ramy czasowe: 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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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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
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DHA t1/2 Summary Statistics for Participants With BCS of 5 in the Primary Analysis Population
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Time to Hospital Discharge in the Primary Analysis Population
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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.)
|
Współpracownicy i badacze
Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.
Śledczy
- Główny śledczy: Matthew B Laurens, MD, MPH, University of Maryland School of Medicine
Daty zapisu na studia
Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
29 listopada 2023
Zakończenie podstawowe (Rzeczywisty)
1 kwietnia 2025
Ukończenie studiów (Rzeczywisty)
1 kwietnia 2025
Daty rejestracji na studia
Pierwszy przesłany
20 lutego 2023
Pierwszy przesłany, który spełnia kryteria kontroli jakości
20 lutego 2023
Pierwszy wysłany (Rzeczywisty)
1 marca 2023
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
18 czerwca 2026
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
21 maja 2026
Ostatnia weryfikacja
9 października 2025
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- 19-0007
- 5UM1AI148689-03 (Grant/umowa NIH USA)
Plan dla danych uczestnika indywidualnego (IPD)
Opis planu IPD
Pozbawione elementów umożliwiających identyfikację dane poszczególnych uczestników związane z pierwotną analizą zostaną udostępnione do udostępniania innym badaczom.
Ramy czasowe udostępniania IPD
Dane zostaną udostępnione do udostępnienia po opublikowaniu wyników badania podstawowego, bez daty końcowej.
Kryteria dostępu do udostępniania IPD
Dane będą udostępniane w dostępnej bazie danych, na platformie internetowej.
Naukowcy będą mogli uzyskać dostęp do danych do analiz związanych z proponowanymi celami badań.
Typ informacji pomocniczych dotyczących udostępniania IPD
- PROTOKÓŁ BADANIA
- SOK ROŚLINNY
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Tak
Bada produkt urządzenia regulowany przez amerykańską FDA
Nie
produkt wyprodukowany i wyeksportowany z USA
Tak
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .