Phase 2/3, Open-Label, Comparative Trial Of Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In Children In Africa
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 361
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitologic Response (ACPR) at Day 28 in the Modified Intent-to-treat (mITT) Population
研究概览
简要总结
The primary objective is to confirm the hypothesis that azithromycin used in combination with chloroquine is non-inferior to artemether- Lumefantrine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum in children in African countries.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Girls and boys ≥5 years to ≤12 years (Cohort 1); and ≥6 to ≤59 months of age (Cohort 2) with uncomplicated, symptomatic malaria as indicated by the presence of the following:
- •Blood smears positive for monoinfection with P. falciparum and asexual parasitemia between 1000 -100,000 parasites/µL;
- •Documented fever (38.0°C/100.4°F rectal or tympanic; 37.2°C/99.0°F axillary or 37.5°C/99.5°F oral) or history of fever (as reported by the legally acceptable representative) within the prior 24 hours;
- •Appropriate for outpatient treatment;
- •Blood glucose ≥60 mg/dL;
- •Hemoglobin ≥6 g/dl or hematocrit ≥18% without signs of anemia-induced Congestive Heart Failure (CHF);
- •Negative urine pregnancy test for females ≥10 years of age (and of child bearing potential)
排除标准
- •Peripheral blood smear positive for mixed infection with multiple Plasmodium spp.
- •Severe or complicated malaria including subjects with any of the following:
- •Impaired consciousness (eg, obtundation, unarousable coma), seizures or abnormal neurologic exam suggestive of severe or complicated malaria;
- •Known hemoglobinuria;
- •Jaundice;
- •Respiratory distress;
- •Persistent vomiting;
- •Gross hematuria, as reported by the subject's legally acceptable representative;
- •Recent history of convulsions;
- •Inability to drink or breastfeed;
- •Unable to sit or stand as appropriate for age;
- •Known pregnancy or breast-feeding or positive urine pregnancy test (females ≥10 years of age and of child bearing potential);
- •History of allergy to or hypersensitivity to azithromycin, any macrolide, chloroquine, artemether, any artemisinin derivative, lumefantrine;
- •Any contraindication to any study drug including AZ, CQ and AL;
- •History of treatment with any antimalarial drug (such as halofantrine, chloroquine, quinine, mefloquine, Malarone, SP, artemisinin compounds) or antibacterial with known antimalarial activity (macrolides, doxycycline, clindamycin) within 2 weeks prior to enrollment of a subject (and/or of the mother of a subject who is being breastfed) into the study;
- •Known or suspected cardiovascular, hepatic or renal abnormality that in the opinion of the investigator would place the subject at increased risk to participate in the study.
研究组 & 干预措施
1
干预措施: Azithromycin plus Chloroquine (Drug)
2
干预措施: Artemether-lumefantrine (Drug)
结局指标
主要结局
Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitologic Response (ACPR) at Day 28 in the Modified Intent-to-treat (mITT) Population
时间窗: Day 28
ACPR (PCR-corrected) was defined as asexual Plasmodium falciparum (P.falciparum) parasitologic clearance at Day 28 irrespective of axillary, oral, rectal, or tympanic temperature, without previously meeting the criteria of Early Treatment Failure (ETF) (see measure description in secondary outcome measures 7 and 8) or PCR-corrected Late Treatment Failure (LTF) (which includes PCR-corrected Late Clinical Failures \[LCF\] - see measure description in secondary outcome measure 9 and 10, and PCR-corrected Late Parasitologic Failures (LPF)- see measure description in secondary outcome measure 11 and 12). PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.
Percentage of Participants With PCR-corrected ACPR at Day 28 in Per-Protocol (PP) Population
时间窗: Day 28
ACPR (PCR-corrected) was defined as asexual P.falciparum parasitologic clearance at Day 28 irrespective of axillary, oral, rectal, or tympanic temperature, without previously meeting the criteria of ETF (see measure description in secondary outcome measures 7 and 8) or PCR-corrected LTF (which includes PCR-corrected LCF - see measure description in secondary outcome measure 9 and 10, and PCR-corrected LPF - see measure description in secondary outcome measure 11 and 12). PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.
次要结局
- Percentage of Participants With PfCRT in True Failures(Baseline to Day 42)
- Percentage of Participants With PCR-corrected ACPR in the mITT Population(Days 7, 14, 21, 35, 42)
- Percentage of Participants With PCR-corrected ACPR in PP Population(Days 7, 14, 21, 35, 42)
- Percentage of Participants With PCR-uncorrected ACPR in the mITT Population(Days 7, 14, 21, 28, 35, 42)
- Percentage of Participants With PCR-uncorrected ACPR in PP Population(Days 7, 14, 21, 28, 35, 42)
- Percentage of Participants With Early Treatment Failure (ETF) in the mITT Population (PCR-corrected)(Day 0 up to Day 3)
- Percentage of Participants With ETF in PP Population (PCR-corrected)(Day 0 up to Day 3)
- Percentage of Participants With Late Clinical Failure (LCF) in the mITT Population (PCR-corrected)(Days 7, 14, 21, 28, 35, 42)
- Percentage of Participants With LCF in PP Population (PCR-corrected)(Days 7, 14, 21, 28, 35, 42)
- Percentage of Participants With Late Parasitologic Failure (LPF) in the mITT Population (PCR-corrected)(Days 7, 14, 21, 28, 35, 42)
- Percentage of Participants With LPF in PP Population (PCR-corrected)(Days 7, 14, 21, 28, 35, 42)
- Percentage of Participants With Asexual Parasitologic Response (PCR-corrected)(Day 7, 14, 21, 28, 35, 42)
- Percentage of Participants With Gametocytologic Response(Days 7, 14, 21, 28, 35, 42)
- Nadir Hemoglobin Level(Day 0 through Day 3)
- Change From Nadir Hemoglobin Level at Days 14, 28, and 42(Day 14, 28, 42)
- Fever Clearance Time(Baseline to Day 42)
- Asexual Plasmodium Falciparum Parasite Clearance Time(Baseline to Day 42)
- Time to Recurrence of Parasitemia(Baseline (Day 0) to Day 42)
- Number of Participants With Recurrent Parasitemia Versus Baseline Plasmodium Falciparum Chloroquine Resistance Transporter (PfCRT) Status(Baseline to Day 42)