New trial for sickle cell disease opens in Uganda
07 Feb 2024
A new trial investigating the best way to treat sickle cell disease in Ugandan children has opened to much enthusiasm. H-PRIME recruited its first participant in mid-January 2024 and since then has already recruited more than 50 children.
Sickle cell disease is an inherited disorder caused by abnormal red blood cells, most commonly found in sub-Saharan Africa. It can lead to chronic anaemia, intermittent painful episodes called sickle cell crises and progressive multi-organ deterioration. Without treatment, sickle cell disease frequently leads to both disability and early death.
H-PRIME aims to identify simple and affordable interventions to improve long-term survival and quality of life for children with sickle cell disease in sub-Saharan Africa.
Previous studies in high-income countries have shown that hydroxyurea can safely and effectively treat sickle cell disease. However, the usual approach to treatment requires close laboratory monitoring to find the right dose, which is not practical or available in low-income settings. Therefore, H-PRIME will compare a high dose with a low dose of hydroxyurea, given pragmatically without extensive monitoring.
Since malaria and bacterial infections are probably the most common cause of early death among children with sickle cell disease in sub-Saharan Africa, H-PRIME also includes comparisons of two antimalarial and two antimicrobial regimens, in a 2x2x2 factorial design. This means that each participant is randomised in three independent comparisons:
- In the first comparison, participants are randomly assigned to receive either a high or low dose of hydroxyurea.
- In the second comparison, participants are randomly assigned to receive either the current standard of care antimalarial treatment (suphadoxine-pyramethamine) or dihydroartemisinin-piperoquine.
- In the third comparison, participants are randomly assigned to receive either the standard of care antimicrobial (penicillin) to prevent bacterial infections or cotrimoxazole.
The H-PRIME team plan to recruit 1,800 children in total from four clinical centres in eastern Uganda, and recruitment is planned to continue for one year. The researchers will then follow up the trial participants until January 2028.
The trial is sponsored by Imperial College London and coordinated at Mbale Clinical Research Institute, Uganda and KEMRI-Wellcome Trust Research programme, Kenya. The MRC Clinical Trials Unit at UCL is leading on the design and statistical aspects of the trial. H-PRIME is supported by grant funding from the Joint Global Health Trials board (Medical Research Council UK), the UK Department for International Development, and the Wellcome Trust.