IV Artesunaten altistumis-vasteen arviointi lapsilla, joilla on vaikea malaria
torstai 21. toukokuuta 2026 päivittänyt: National Institute of Allergy and Infectious Diseases (NIAID)
Tässä tutkimuksessa ugandalaiset lapset, joilla on diagnosoitu vaikea malaria, saavat suonensisäistä (IV) artesunaattia Maailman terveysjärjestön (WHO) ohjeiden mukaisesti.
Tutkimuksen yleiskatsaus
Yksityiskohtainen kuvaus
Huolimatta viimeaikaisista edistysaskeleista malarian torjunnassa, Plasmodium falciparum tappaa edelleen lähes puoli miljoonaa ihmistä vuosittain, joista suurin osa on Saharan eteläpuolisessa Afrikassa asuvia lapsia. Plasmodium falciparum on malarialoisen yleisin laji ja se aiheuttaa vakavimman sairauden ja kuoleman. Se vastasi 99,7 % kaikista malariatapauksista Maailman terveysjärjestön (WHO) Afrikan alueella vuonna 2018. Alle 5-vuotiaat lapset ja raskaana olevat naiset ovat eniten alttiita malarialle ja kuolemaan, ja heidän osuus on 67 prosenttia arvioiduista 405 000 malariakuolemasta maailmanlaajuisesti, ja näistä 94 prosenttia on Afrikan alueella. Vaikka malariakuolemien kokonaismäärä väheni vuonna 2018 vuoteen 2010 verrattuna, malariakuolleisuuden vähenemisaste hidastui vuodesta 2016 lähtien, ja tämä on saanut malariatutkijat kyseenalaistamaan, ovatko nykyiset malarian hoito-ohjelmat optimaaliset ja perustuvatko vankkaan tieteelliseen näyttöön.
Vaikea malaria on lääketieteellinen hätätilanne, joka ilman välitöntä hoitoa johtaa 100-prosenttiseen kuolleisuuteen. On olennaista, että erittäin tehokkaan malarialääkkeen pitoisuudet plasmassa saavutetaan mahdollisimman nopeasti. Artesunaatti on vesiliukoinen hemisukkinaatti-artemisiniinijohdannainen, jota on saatavana natriumhemisukkinaattisuolana injektiota varten. Artesunaten erinomaista malariaa ehkäisevää ominaisuutta, jonka osoittaa nopea loisten poistuminen, vahvistaa sen korkea alkumaksimipitoisuus (Cmax) ja nopea hydrolyysi sen aktiiviseksi metaboliitiksi dihydroartemisiniiniksi (DHA).
Nykyiset IV-artesunaatin annostusohjelmat perustuvat loisten puhdistumiseen kuluvaan aikaan eivätkä parasitemian aiheuttamiin fysiologisiin muutoksiin liittyviin kliinisiin päätepisteisiin. Muita fysiologisen toimintahäiriön mittareita voidaan käyttää tutkimuksen päätepisteinä malarian hoidon tulosanalyysissä nykyisten IV artesunaatin hoito-ohjelmien osalta vaikean malarian hoidossa. Parannetut annostusohjelmat johtavat vähemmän komplikaatioihin ja todennäköisesti vähemmän kuolemaan. Tällaista strategiaa tarvitaan, jotta voidaan edelleen vähentää kansanterveyshyötyjä malariakuolleisuutta vastaan, joka näyttää hiljattain pysähtyneen.
Lapsipotilaille laskimonsisäinen artesunaatin annostus perustuu painoon, jotta se mukautuu artesunaatin puhdistumaan, ja se on kehitetty parasitemian puhdistumaan kuluvan ajan perusteella, mikä ei välttämättä kuvasta täysin kliinistä paranemista. P. falciparum -loiset tunnetaan kyvystään infektoida punaisia verisoluja, jotka sitten näyttävät muunnelmia pinta-antigeenejä, jotka kiinnittyvät endoteelisuonistoon kohde-elimissä. Tästä syystä loisten puhdistuman mittaus ääreisverestä ei välttämättä heijasta vakavan malarian fysiologisia vaikutuksia, jotka johtuvat pääteelinten vaurioista, joko verenkierron suorasta heikkenemisestä ja hapen toimitusten heikkenemisestä, paikallisesta tulehdusreaktiosta, joka kohdistuu infektoituneita punasoluja vastaan. kiinnittynyt verisuonten endoteeliin tai infektoituneiden ja infektoimattomien punasolujen ruusuutuminen verisuonistoon. Muut fysiologisen toimintahäiriön mittaukset, kun ne mitataan yksinään tai algoritmisesti, kuten pisteet, voivat paremmin kuvastaa onnistunutta hoitoa, mukaan lukien seerumin laktaatti, seerumin glukoosi, bikarbonaattitasot, BCS, kreatiniini ja hemoglobiini. Nämä toimenpiteet, verrattuna tavallisiin loisten poistumisaikoihin ääreisverestä, voivat olla tärkeämpiä määritettäessä malarialääkkeen farmakologista annostusta ja liittyä siihen.
Tämän tutkimuksen tavoitteena on kehittää parannettu IV artesunaattiannostusohjelma lasten vaikean malarian hoitoon.
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
90
Vaihe
- Vaihe 4
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Kampala, Uganda
- Makerere University-Infectious Diseases Institute
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
6 kuukautta - 14 vuotta (Lapsi)
Hyväksyy terveitä vapaaehtoisia
Ei
Tutkimusväestö
Tähän tutkimukseen otetaan mukaan 6 kuukauden–14-vuotiaita ugandalaisia lapsia, joilla on diagnosoitu vakava malaria Maailman terveysjärjestön (WHO) standardoitujen kriteerien mukaisesti (kaikki P. falciparum -parasitemia ja vaaramerkkien esiintyminen).
Kuvaus
Sisällyttämiskriteerit:
- Lapset iältään 6 kuukautta - 14 vuotta vakavan malariadiagnoosin hetkellä, mukaan lukien
- Täytä vakavan malarian tapauksen määritelmä WHO:n standardisoitujen ohjeiden mukaisesti
- Vanhempi/huoltaja on valmis antamaan tietoisen suostumuksen
- Suostumus 8–14-vuotiaille lapsille, jotka ovat tajuissaan ja muutoin pystyvät antamaan suostumuksen, mukaan lukien
- Asuu Tororon alueella tai sen lähellä Ugandassa
Poissulkemiskriteerit:
- Yli 24 tunnin artemisiniinihoidon vastaanotto
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: Käsivarsi 1
Osallistujat saavat standardinmukaista hoitoa IV artesunateilla vaikean malarian hoitoon.
Jokainen 60 mg:n artesunihappopullo liuotetaan 1 ml:aan 5-prosenttista natriumbikarbonaattia natriumartesunaatin muodostamiseksi ja sekoitetaan sitten 5 ml:aan 5-prosenttista dekstroosia.
Tämä ruiskutetaan boluksena pysyvään IV-kanyyliin.
Lapset, jotka painavat alle 20 kg, saavat IV artesunaattia annoksella 3,0 mg/kg/annos verrattuna vanhempiin lapsiin, jotka painavat >/= 20 kg ja jotka saavat 2,4 mg/kg/annos, aikoina 0, 12, 24.
Jos ei pysty ottamaan suun kautta otettavaa lääkitystä, IV artesunaatin antamista jatketaan 48 ja 72 tunnin kohdalla.
Lapset, jotka toipuvat ja pystyvät siirtymään oraaliseen malariahoitoon vähintään 24 tunnin kuluttua, aloittavat 3 päivän suun kautta otettavan artemisiniini-yhdistelmähoidon kansallisten ohjeiden mukaisesti.
N = 100
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Artesunaatti on artemetrin meripihkahappoesteri.
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Maximum Concentration (Cmax) of Dihydroartemisinin (DHA)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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.
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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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Serum glucose was recorded daily until discharge along with scheduled follow-up visits.
Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge.
Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose.
Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints.
To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.
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Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
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Change From Baseline in Total Bilirubin in the Primary Analysis Population
Aikaikkuna: 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)
|
|
Change From Baseline in Total Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Time to Hospital Discharge in the Primary Analysis Population
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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.)
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Tutkijat
- Päätutkija: Matthew B Laurens, MD, MPH, University of Maryland School of Medicine
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Keskiviikko 29. marraskuuta 2023
Ensisijainen valmistuminen (Todellinen)
Tiistai 1. huhtikuuta 2025
Opintojen valmistuminen (Todellinen)
Tiistai 1. huhtikuuta 2025
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Maanantai 20. helmikuuta 2023
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Maanantai 20. helmikuuta 2023
Ensimmäinen Lähetetty (Todellinen)
Keskiviikko 1. maaliskuuta 2023
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Torstai 18. kesäkuuta 2026
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Torstai 21. toukokuuta 2026
Viimeksi vahvistettu
Torstai 9. lokakuuta 2025
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- 19-0007
- 5UM1AI148689-03 (Yhdysvaltain NIH-apuraha/sopimus)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
IPD-suunnitelman kuvaus
Primäärianalyysiin liittyvät yksilöimättömät yksittäiset osallistujatiedot asetetaan jaettavaksi muiden tutkijoiden kanssa.
IPD-jaon aikakehys
Tiedot asetetaan jaettavaksi ensisijaisten tutkimustulosten julkaisemisen yhteydessä ilman päättymispäivää.
IPD-jaon käyttöoikeuskriteerit
Tiedot asetetaan saataville saatavilla olevassa tietokannassa online-alustalla.
Tutkijat pääsevät käsiksi ehdotettuihin tutkimustavoitteisiinsa liittyviin analyyseihin.
IPD-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
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