Sickle Cell Disease - Stroke Prevention in Nigeria Trial
Condition: Sickle Cell Anemia; Sickle Cell Disease; Stroke
MeSH terms: Stroke; Anemia, Sickle Cell
Study type: Interventional

Summary: 
      Given large absolute numbers of individuals with sickle cell disease in Nigeria, hydroxyurea
      therapy for all individuals with sickle cell disease may not be initially feasible; however,
      a targeted strategy of hydroxyurea use for primary prevention of strokes is an alternative to
      the standard therapy (observation) for high-risk individuals. The investigators propose a
      feasibility study, Sickle Cell Disease - Stroke Prevention in Nigeria (SPIN) Trial, to
      determine whether hydroxyurea can be used for primary prevention of strokes in Nigerian
      children with sickle cell anemia.
    

Detailed description: 
      Sickle cell disease (SCD) is the most common genetic disease in the world. Approximately
      150,000 Nigerian children are born each year with SCD, making it the country with the largest
      burden of sickle cell disease in the world. SCD is the most common cause of stroke in
      children and results in considerable morbidity in affected children. The current primary
      prevention approach of regular monthly blood transfusion therapy of children at high risk of
      stroke (identified by elevated transcranial Doppler measurements) is not feasible in a low
      income country such as Nigeria due to scarcity of supply, cost, and high rate of blood borne
      infections. In the United States, hydroxyurea (HU) is standard therapy for adults with SCD
      and may be a reasonable prevention alternative to regular blood transfusion for treatment of
      primary stroke in high-risk children. Given large absolute numbers of individuals with SCD in
      Nigeria, HU therapy for all individuals with SCD may not be initially feasible; however, a
      targeted strategy of HU use for primary prevention of strokes is an alternative to the
      standard therapy (observation) for high-risk individuals. Study investigators therefore
      propose a feasibility study to determine the acceptability of HU for primary prevention of
      strokes in Nigerian children with sickle cell anemia (SCA) in preparation for a National
      Institute of Health (NIH) sponsored Phase III Trial. Investigators will establish a safety
      protocol for using HU in a clinical trial setting and complete the necessary preparations for
      a definitive phase III trial. To accomplish these aims study investigators have assembled a
      strong multidisciplinary team representing Vanderbilt University and two premier in-country
      institutions: Aminu Kano Teaching Hospital, Nigeria, and Friends in Global Health-Nigeria.
      Completion of a definitive trial will not only benefit children with SCA in sub-Saharan
      Africa, where the majority of children with SCA live in the world, but could provide
      reasonable evidence for an alternative to blood transfusion therapy for the primary
      prevention of strokes in the US. To our knowledge this would be the first stroke prevention
      trial in Nigeria and could establish a precedent to expand to secondary stroke prevention for
      children and adults with SCA, as regrettably, no therapy is available to prevent recurrent
      stroke in these high-risk patients in resource-poor nations.
    

Intervention name(s): Hydroxyurea
Intervention type(s): Drug
Intervention description(s): Hydroxyurea will be prescribed as an investigational therapy by the treating physician. Recommended guidelines for titration of hydroxyurea to maximal tolerated dose are below. The study intervention will include hydroxyurea to begin at ~20 mg/kg/day (range 17.5 - 26 mg/kg/day). No dose escalation will occur as this dose was shown to have some efficacy in infants with SCA and was associated with rare myelosuppression.(1)
Other intervention name(s): Droxia; Hydrea; Mylocel
Intervention MeSH terms: Hydroxyurea
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: transcranial Doppler; stroke; sickle cell anemia; Nigeria; hydroxyurea; low income country