Primary stroke prevention in Nigerian children with sickle cell disease (SPIN): Challenges of conducting a feasibility trial

Background: The majority of children with sickle cell disease (SCD), approximately 75%, are born in sub-Saharan Africa. For children with elevated transcranial Doppler (TCD) velocity, regular blood transfusion therapy for primary stroke prevention is standard care in high income countries, but is not feasible in sub-Saharan Africa. Procedure: In the first U.S. National Institute of Health (NIH) sponsored SCD clinical trial in sub-Saharan Africa, we describe the protocol and challenges unique to starting a clinical trial in this region. We are conducting a single arm pilot trial of hydroxyurea therapy in children with TCD velocity ≥200cm/sec in the middle cerebral arteries. Eligible children will be placed on hydroxyurea (n=40) and followed for 3 years at Aminu Kano Teaching Hospital, Nigeria. Adherence will be measured via the Morisky Scale and adverse events will be determined based on hospitalization. Results: Originally, a randomized placebo trial was planned; however, placebo was not approved by the local Ethics Committee. Hence a single arm trial of hydroxyurea will be conducted and five controls per patient with normal TCD measurements will be followed to compare the rate of adverse events to those with abnormal TCD measurements taking hydroxyurea. Using non-NIH funding, over 9 months, multiple face-to-face investigator meetings were conducted to facilitate training. Conclusion: A hydroxyurea trial (NCT01801423) for children with SCD is feasible in sub-Saharan Africa; however, extensive training and resources are needed to build a global patient oriented multi-disciplinary research team with a common purpose.