Dihydroartemisinin-Piperaquine or Sulphadoxine-Pyrimethamine for the Chemoprevention of Malaria in Children With Sickle Cell Anaemia in Eastern and Southern Africa: a Double Blind Randomised Trial (CHEMCHA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 723
- 试验地点
- 3
- 主要终点
- Incidence of clinical malaria
研究概览
简要总结
Sickle Cell Anaemia (SCA) is an inherited disease that makes the body produce red blood cells with abnormal sickle-shaped cells. The sickle-shaped cells are rigid, not flexible and break up easily resulting in anaemia. The abnormal cells also stick to the vessel walls, causing a blockage that slows or stops the flow of blood. When this happens, oxygen cannot reach nearby tissues. The lack of oxygen can cause attacks of sudden, severe pain, called pain crises, stroke or damage to important organs such as the spleen. All of these can lead to death. These attacks can occur without warning and are often started and made worse by infections such as malaria. Therefore, in many countries in Africa where malaria is common, children with SCA are given malaria medicines to prevent the infection. However, many of the medicines do not work effectively, are too difficult to take or they have side effects, resulting in poor adherence.
The aim of this study is to find safe, acceptable and effective medicines for malaria prevention in children with SCA in eastern and southern Africa. The investigators propose to conduct a study to find out whether giving weekly doses of dihydroartemisinin-piperaquine, also called DP, is safe, more effective, acceptable and cost-effective than the current strategy of monthly sulphadoxine-pyrimethamine (SP) to prevent malaria in children with sickle cell anaemia. Overall, 548 children aged 6 months to 15 years will be chosen randomly to receive either weekly DP or monthly SP for about 18 months. To test if the study medicine is effective, the study will compare the case burden of malaria. The investigators will also monitor every child for any type of illness, blood transfusions and other complications of sickle cell anaemia and admissions to the hospital. In addition, the study will evaluate the impact of DP on the development of resistance by malaria parasites. The study will also include nested safety studies on the effect of DP on the heart. All study participants will receive all the other usual care and treatments, including patient education on home care, and daily penicillin if younger than 5 years. If proven safe and efficacious, chemoprophylaxis with DP may decrease the incidence of malaria in children with SCA, prevent ill-health and deaths, and improve wellbeing.
详细描述
Background and rationale:
An estimated 300,000 babies are born with Sickle Cell Anaemia (SCA) annually. Affected children have chronic ill health and many suffer a premature death. Ill health is commonly precipitated by febrile illnesses including malaria. Antimalarial chemoprophylaxis is an important strategy, but current regimes are either sub-optimally effective (e.g., monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g., daily proguanil). The investigators propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa.
Objectives:
Our objective is to determine the efficacy, safety, uptake, and cost-effectiveness of malaria chemoprevention with weekly single day courses of DP vs monthly single day courses of SP in children with SCA in eastern and southern Africa.
Hypothesis:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This will be a double-blinded study. Patients on DP will also receive SP placebo, and those on SP will in addition, receive DP placebo. All laboratory staff will be masked to the treatment assignment of individual participants. The trial statistician will also be blinded regarding the treatment code when he/she develops the statistical analysis plan and writes the statistical programmes, which will be validated and completed using dummy randomisation codes.
入排标准
- 年龄范围
- 6 Months 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Known chronic disease e.g. congenital heart disease;
- •Known red cell disorder e.g. thalassaemia, glucose-6-phosphate dehydrogenase deficiency;
- •Known allergy to DP or SP;
- •Receiving daily cotrimoxazole prophylaxis;
- •Unlikely to comply with the follow-up schedule;
- •Participating in another trial
研究组 & 干预措施
Intervention arm
The intervention will be oral dihydroartemisinin (20mg) and piperaquine (160 mg) and administered once weekly at approximate doses of dihydroartemisinin 2.5mg/kg/day and piperaquine 20mg/kg/day based on participants' weight categories
干预措施: Dihydroartemisinin Piperaquine (Drug)
Comparator
The active control will be Sulphadoxine-Pyrimethamine (SP), the current standard of care for malaria chemoprevention for SCA in Uganda and Malawi. This will also be provided by Guilin Pharmaceutical Co. Ltd as their generic World Health Organization-approved sulphadoxine-pyrimethamine 500/25mg tablets. It will be administered as monthly single-day courses of SP at approximate doses of S=25mg/kg and P=1.25mg/kg.
干预措施: Dihydroartemisinin Piperaquine (Drug)
结局指标
主要结局
Incidence of clinical malaria
时间窗: 18 months
An episode of malaria will be defined as a history of fever in the preceding 48hrs or documented axillary temperature ≥37.5 degrees centigrade plus microscopy confirmed Plasmodium falciparum malaria
次要结局
- All cause sick visits(18 months)
- All-cause and malaria-specific hospitalisation(18 months)
- Serious adverse events(18 months)
- Other gastro-intestinal complaints(18 months)
- Provider costs(18 months)
- Incidence of malaria parasitaemia(18 months)
- Death(18 months)
- Malaria specific sick visits(18 months)
- QTc prolongation(18 months)
- Serious cardiac adverse events(18 months)
- Tolerance - vomiting(18 months)
- Level of adherence(18 months)
- Direct and indirect costs(18 months)
- Sickle Cell Anaemia-related vaso-occlusive events(18 months)
- Incremental cost-effectiveness(18 months)