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Background: Nigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health-funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention., Methods: This is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA., Results: As part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke., Conclusions: Our trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [ S troke Pr evention i n N i g eria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

Background: Although Nigeria has the highest burden of sickle cell disease (SCD) worldwide, there is still variable and poor utilisation of standard-of-care practices for SCD patients in the country., Methods: This was a questionnaire survey of doctors in some dedicated SCD clinics in Nigeria in order to document the facilities available and common management practices., Results: There were responses from 18 clinics based in 11 institutions. The number of patients being followed in each centre ranged from 15 to approximately 11 000. All clinics provided malaria prophylaxis and folic acid routinely to their patients. Only eight clinics prescribe penicillin prophylaxis. Eight prescribe hydroxyurea to patients who can afford it when indicated. All of the centres except three have electronic cell counters, but all had access to haemoglobin electrophoresis. Three had high-performance liquid chromatography machines installed but none was being routinely used. One institution had a functioning molecular biology laboratory. There is no official newborn screening programme in the country. All had access to microbiology and chemistry laboratories. Nine institutions had CT, six had MRI and three had transcranial Doppler facilities., Conclusion: The care available for SCD in Nigeria is still suboptimal and there is an urgent need for concerted effort to tackle the problem, but to make a significant impact on the burden of the disease would require more focus at the primary care level. Some steps to achieving this are outlined.