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중증 말라리아 환아에서 IV Artesunate의 노출-반응 평가

2026년 5월 21일 업데이트: National Institute of Allergy and Infectious Diseases (NIAID)
이 연구에서 중증 말라리아 진단을 받은 우간다 어린이들은 세계보건기구(WHO) 지침에 따라 정맥 주사(IV) 아르테수네이트를 투여받게 됩니다.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

말라리아 통제의 최근 발전에도 불구하고 열대열원충은 매년 거의 50만 명을 계속해서 죽이고 있으며 이들 중 대부분은 사하라 이남 아프리카에 사는 어린이들입니다. Plasmodium falciparum은 가장 널리 퍼진 말라리아 기생충 종이며 가장 심각한 형태의 질병과 사망의 원인입니다. 2018년 세계보건기구(WHO) 아프리카 지역 전체 말라리아 사례의 99.7%를 차지했습니다. 5세 미만의 어린이와 임산부는 말라리아와 사망의 위험이 가장 높으며, 전 세계적으로 추정되는 405,000명의 말라리아 사망자 중 67%를 차지하며, 이 중 94%는 아프리카 지역에서 발생합니다. 2010년에 비해 2018년에 말라리아 사망이 전반적으로 감소했지만 2016년 이후로 말라리아 사망률 감소율이 둔화되었으며 이로 인해 말라리아 연구자들은 현재의 말라리아 치료 요법이 최적이고 건전한 과학적 증거를 기반으로 하는지 의문을 갖게 되었습니다.

중증 말라리아는 즉시 치료하지 않으면 100% 사망하는 의학적 응급 상황입니다. 매우 효과적인 항말라리아 약물의 혈장 농도가 가능한 한 빨리 달성되는 것이 기본입니다. Artesunate는 수용성 헤미석시네이트 아르테미시닌 유도체로 주사용 헤미석시네이트 나트륨 염으로 사용할 수 있습니다. 빠른 기생충 제거로 입증된 Artesunate의 우수한 항말라리아 특성은 높은 초기 최대 농도(Cmax)와 활성 대사체인 DHA(dihydroartemisinin)로의 빠른 가수분해로 강화됩니다.

IV 아르테수네이트의 현재 투여 요법은 기생충 제거까지의 시간을 기반으로 하며 기생충혈증에서 발생하는 생리학적 변화와 관련된 임상적 종점이 아닙니다. 생리학적 기능 장애의 다른 척도는 중증 말라리아 치료를 위한 IV 아르테수네이트에 대한 현재 요법의 말라리아 치료 결과 분석을 위한 연구 종점으로 사용될 수 있습니다. 개선된 투약 요법은 더 적은 합병증과 더 적은 사망으로 이어질 것입니다. 이러한 전략은 최근 정체된 것으로 보이는 말라리아 사망률에 대한 공중 보건 이익을 더욱 줄이기 위해 필요합니다.

소아 환자의 경우 IV 아르테수네이트 투여는 체중을 기준으로 하여 아르테수네이트 청소율을 조정하고 기생충혈증 제거 시간까지의 시간을 기준으로 개발되었으므로 임상 치료가 완전히 반영되지 않을 수 있습니다. P. falciparum 기생충은 표적 기관의 내피 맥관 구조에 부착하는 변이 표면 항원을 표시하는 적혈구를 감염시키는 능력으로 알려져 있습니다. 이러한 이유로 말초 혈액에서 기생충 제거 측정은 감염된 적혈구에 대한 국소 염증 반응인 혈류의 직접적인 손상과 산소 전달 감소를 통해 말단 장기 손상으로 인한 중증 말라리아의 생리학적 영향을 반영하지 않을 수 있습니다. 혈관 내피에 부착되거나 맥관구조에서 감염된 적혈구와 감염되지 않은 적혈구의 로제팅. 생리학적 기능 장애의 다른 척도는 단독으로 또는 점수와 같은 알고리즘 방식으로 정량화될 때 혈청 젖산염, 혈청 포도당, 중탄산염 수치, BCS, 크레아티닌 및 헤모글로빈을 포함하여 성공적인 치료를 보다 정확하게 반영할 수 있습니다. 이러한 측정은 말초 혈액의 표준 기생충 제거 시간과 비교하여 항말라리아 요법의 약리학적 투여량을 정량화하고 관련시키는 데 더 중요할 수 있습니다.

이 연구는 어린이의 중증 말라리아 치료를 위한 개선된 IV 아르테수네이트 투여 요법을 개발하는 것을 목표로 합니다.

연구 유형

중재적

등록 (실제)

90

단계

  • 4단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

6개월 (어린이)

건강한 자원 봉사자를 받아들입니다

아니

연구 인구

이 연구는 표준화된 세계보건기구(WHO) 기준(P. falciparum 기생충 및 위험 징후의 존재)에 따라 중증 말라리아로 진단된 6개월에서 14세 사이의 우간다 어린이를 등록하고 있습니다.

설명

포함 기준:

  • 중증 말라리아 진단 당시 6개월에서 14세 사이의 어린이
  • WHO 표준화 지침에 따라 중증 말라리아에 대한 사례 정의 충족
  • 정보에 입각한 동의를 제공할 의향이 있는 부모/보호자
  • 의식이 있고 다른 방식으로 동의를 제공할 수 있는 8세에서 14세 사이의 아동을 위한 동의, 포괄적
  • 우간다 토로로 지구 또는 인근에 거주

제외 기준:

  • 24시간 이상 아르테미시닌 요법을 받은 경우

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 팔 1
참가자들은 중증 말라리아 치료를 위해 IV 아르테수네이트로 표준 치료를 받게 됩니다. 각 60mg의 아르테순산 바이알을 5% 중탄산나트륨 1mL에 용해하여 아르테순산나트륨을 형성한 다음 5% 덱스트로스 5mL와 혼합합니다. 이것은 유치 IV 캐뉼라에 볼루스로 주입됩니다. 체중이 20kg 미만인 어린이는 0, 12, 24회에 2.4mg/kg/용량을 투여받는 체중이 20kg 이상인 어린이와 비교하여 3.0mg/kg/용량의 IV 아르테수네이트를 투여받게 됩니다. 경구 약물을 복용할 수 없는 경우 IV artesunate는 48시간과 72시간 동안 계속됩니다. 최소 24시간 후에 회복되어 경구 항말라리아 치료로 전환할 수 있는 어린이는 국가 지침에 따라 3일 경구 아르테미시닌 복합 치료 과정을 시작하게 됩니다. N = 100
의약품: 아르테수네이트
Artesunate는 artemether의 숙신산 에스테르입니다.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Maximum Concentration (Cmax) of Dihydroartemisinin (DHA)
기간: Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Population Pharmacokinetic (PK) modeling was conducted to derive Cmax from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.
Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Area Under the Curve Over 0-12 Hours (AUC0-12) of DHA
기간: Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)

Population PK modeling was conducted to derive AUC0-12 from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.

Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Half-life (t1/2) of DHA
기간: Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Population PK modeling was conducted to derive t1/2 from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.
Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Time to Cmax (Tmax) of DHA
기간: Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Population Pharmacokinetic (PK) modeling was conducted to derive PK parameters from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin. From the simulation, the Tmax was assumed to be 0 as the simulation replicates artesunate administered as an IV bolus directly into the central compartment.
Day 1(Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)
Change From Baseline in Temperature in the Primary Analysis Population
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK Parameters (AUC0-12, Cmax, and t1/2) and temperature. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Temperature in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and temperature. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline Systolic Blood Pressure (BP) in the Primary Analysis Population
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline Systolic BP in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline Diastolic BP in the Primary Analysis Population
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and diastolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline Diastolic BP in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and diastolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From in Venous Serum Lactate in the Primary Analysis Population
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Serum lactate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From in Venous Serum Lactate in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Serum lactate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Serum Bicarbonate in the Primary Analysis Population
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Serum Bicarbonate in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Serum Glucose in the Primary Analysis Population
기간: 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Serum glucose was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.
24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Serum Glucose in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Serum glucose was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Total Bilirubin in the Primary Analysis Population
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Total bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.
Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time of completion of planned IV Artesunate dosing (72 hours post-first IV Artesunate dose), and Time of first hospital discharge (up to day 9)
Change From Baseline in Total Bilirubin in the Subset Who Did Not Receive Any IV Artesunate or Other Artemisinin-based Therapy Before Enrollment
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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
기간: Baseline, 24 hours post-first IV Artesunate dose, 48 hours post-first IV Artesunate dose, Time 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)

2차 결과 측정

결과 측정
측정값 설명
기간
Time to Hospital Discharge in the Primary Analysis Population
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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.)

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Institute of Allergy and Infectious Diseases (NIAID)

협력자

University of Maryland, Baltimore
Makerere University

수사관

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

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2023년 11월 29일

기본 완료 (실제)

2025년 4월 1일

연구 완료 (실제)

2025년 4월 1일

연구 등록 날짜

최초 제출

2023년 2월 20일

QC 기준을 충족하는 최초 제출

2023년 2월 20일

처음 게시됨 (실제)

2023년 3월 1일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 6월 18일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 5월 21일

마지막으로 확인됨

2025년 10월 9일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 19-0007
  • 5UM1AI148689-03 (미국 NIH 보조금/계약)

개별 참가자 데이터(IPD) 계획

IPD 계획 설명

기본 분석과 관련된 익명화된 개별 참가자 데이터는 다른 연구자와 공유할 수 있습니다.

IPD 공유 기간

종료일 없이 기본 연구 결과가 게시되면 데이터를 공유할 수 있습니다.

IPD 공유 액세스 기준

데이터는 온라인 플랫폼의 액세스 가능한 데이터베이스에서 사용할 수 있습니다. 연구원은 제안된 연구 목표와 관련된 분석을 위해 데이터에 액세스할 수 있습니다.

IPD 공유 지원 정보 유형

  • 연구_프로토콜
  • 수액

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

예

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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