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)

19-105

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.

2021-04-09

2023-06-30

2023-07-12

Completed

Early phase I

723

Inclusion criteria 1. Children ages 6 months - 15 years 2. Has a laboratory diagnosis of Sickle Cell Anaemia (HbSS) on haemoglobin electrophoresis, High-Performance Liquid Chromatography or Iso-electric focusing; 3. Weighs ≥5kg; 4. The parent has provided written consent. Exclusion Criteria: 1. Known chronic disease e.g. congenital heart disease; 2. Known red cell disorder e.g. thalassaemia, glucose-6-phosphate dehydrogenase deficiency; 3. Known allergy to DP or SP; 4. Receiving daily cotrimoxazole prophylaxis; 5. Unlikely to comply with the follow-up schedule; 6. Participating in another trial

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This will be a randomized, double-blind, parallel-group superiority trial of weekly single-day courses of DP for an average of 18 months compared to monthly single-day courses of SP in SCA patients. The study will be conducted in Uganda and Malawi, using randomisation stratified by bodyweight and study centre. Participants will be randomized using an allocation of 1:1 to DP or SP. Patients on DP will also receive an SP placebo, and those on SP will in addition, receive a DP placebo', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': '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.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 723, 'type': 'ACTUAL'}}

2023-09-13