Can Triple Artemisinin-based Combination Therapy for Treatment of Uncomplicated Plasmodium Falciparum Malaria, Delay Drug Resistance Development of Plasmodium Falciparum in Tanzania: a Randomized Three Arm Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 384
- 试验地点
- 4
- 主要终点
- Crude recurrent parasitemia by day 56 in the respective arms
研究概览
简要总结
Background: Artemisinin resistance has emerged in parts of Southeast Asia, and there are reports in Africa of reduced susceptibility of Plasmodium falciparum parasites against artemisinin-based combination therapy (ACT). No new drugs are available in the pipeline to replace ACTs in case they fail.
This study aims to assess whether a sequential administration of triple ACTs with different partner-drugs can improve the efficacy of ACT for treatment of uncomplicated malaria.
Methods: A health facility-based, three-arm partially blinded randomized clinical trial will be conducted to assess efficacy and safety of a sequential administration of artemether-lumefantrine followed immediately by artesunate-amodiaquine (AL+ASAQ) or artemether-lumefantrine with by amodiaquine (AL+AQ) compared to artemether-lumefantrine plus placebo (AL+PBO). Eligible children aged 6 - 120 months and with microscopy confirmed uncomplicated P. falciparum malaria will be enrolled, administered with trial medicines and followed-up at 0 (just prior to first drug intake) and 8 hours on day 0, 12 hourly on days 1, 2, 3, 4, 5, followed by once daily on days 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 35, 42 and 56 for clinical and laboratory evaluations. Clinical evaluation will involve assessment of signs and symptoms related to the disease and or trial medicine during follow-up. Laboratory evaluation will include microscopic determination of presence of malaria parasites and species, hemoglobin level, molecular analysis for markers of drug resistance and to differentiate recrudescence from new infection. The primary outcome will be Polymerase Chain Reaction (PCR)-adjusted adequate clinical and parasitological cure rate on days 28 and 42.
Expected outcomes: The findings will give an insight on whether 3 ACTs are more efficacious than the use of first-line regimen alone, and are tolerable for treatment of uncomplicated falciparum malaria.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 6 Months 至 120 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients presenting at the health facility with suspected acute uncomplicated malaria will be screened for eligibility.
- •Inclusion Criteria:
- •Age from 6 - 120 months
- •Weight ≥ 5 kg
- •Body temperature ≥37.5°C or history of fever in the last 24 hours
- •Microscopy confirmed P. falciparum mono-infection
- •Parasitemia level of 1000-200000/μL
- •Ability to swallow oral medication
- •Ability and willingness to abide by the study protocol and the stipulated follow-up visits
- •A written proxy informed consent from a parent/guardian
排除标准
- •Children aged below 6 months will not be included in the study because ACTs are contraindicated in this group.
- •Evidence of severe malaria or danger signs
- •Known allergy to trial medicines
- •Reported antimalarial intake ≤2 weeks
- •Haemoglobin <5 g/dL
- •Blood transfusion within last 90 days
- •Febrile condition other than malaria
- •Known underlying chronic or severe disease (including severe malnutrition).
研究组 & 干预措施
Artemether-Lumefantrine alone
a standard 3-days dosage of Artemether-Lumefantrine (20/120mg) followed by placebo for another 3 days
干预措施: Artemether-lumefantrine (Drug)
Artemether-lumefantrine followed by artesunate amodiaquine
a standard 3-days dosage, twice a day course of Artemether-Lumefantrine (20/120mg) immediately followed by a standard 3-days, once a day course of Artesunate-Amodiaquine (40base)
干预措施: Artemether-lumefantrine then Artesunate amodiaquine (Drug)
Artemether-lumefantrine with Amodiaquine
a standard 3-days dosage of Artemether-Lumefantrine (20/120mg) given together with Amodiaquine hydrocloride(40 base) followed by placebo for another 3 days;
干预措施: Artemether-lumefantrine and Amodiaquine Drug Combination (Drug)
结局指标
主要结局
Crude recurrent parasitemia by day 56 in the respective arms
时间窗: 56th day since enrolment
Laboratory assessment of parasitemia using light microscopy performed at last day of follow up will be the primary outcome assessing the differences in proportion of patients with recurrent parasitemia.
次要结局
- PCR adjusted cure rates by day 28, 42 and 56.(Through study completion, an average of 1 year)
研究者
Billy Ngasala
Associate Professor
Uppsala University