Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment

Study Overview
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Brief Summary
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The vast majority of births with sickle cell disease (SCD) occur in Africa and 90% are thought to die before the age of five. Hydroxyurea (HU) is the only drug approved by the FDA for the treatment of sickle cell anemia. Although HU is used to treat small numbers of patients in Africa, cost, fear of toxicity, and lack of awareness and availability limit its use. The leukopenia that may be seen with HU raises the possibility of increased susceptibility to infection. Risk stratification - i.e., identification of patients most likely to benefit- could focus therapy and provide confidence that the risk:benefit ratio is favorable. Several clinical measures of future risk are well defined and findings on modifier genes in the US, primarily related to fetal hemoglobin (HbF), have further improved risk prediction. Whether the genetic variants predict severity in Africa is not known. The investigators have established a SCD cohort in Ibadan, Nigeria. In the first phase of this research the investigators will implement clinical risk examinations and assess the relationship between clinical characteristics (including levels of HbF) and known genetic markers. As a proxy for a birth cohort, the investigators will compare the frequency of the genetic markers in adult patients (i.e., survivors) to children. In the second phase the investigators will randomize 40 high risk adult patients to fixed low dose HU or no HU treatment in a crossover design and monitor hematologic and physiologic parameters to document hematologic effects and safety. This work will lay the basis for a large-scale trial to document safety and efficacy.

Official Title
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Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea

Conditions
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Sickle Cell Disease, Sickle Cell Anemia

Intervention / Treatment
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* Drug: hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years HemoglobinSS (HbSS) or beta-zero (B0) thalassemia genotype Hemoglobin concentration >4.5 g/dL at steady state and time of enrollment Absolute neutrophil count >1,500/mircoliter Platelet count >95,000/microliter Serum creatinine <1.2 mg/dL Alanine transaminase less than two times the upper limit of normal Exclusion Criteria: HIVpositive Hepatitis B and/or C positive

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Adult patients to start to receive fixed low dose hydroxyurea (10 mg/kg) per day for six months and then crossover to no hydroxyurea treatment for six months, or start with no hydroxyurea treatment for six months and then crossover to receive fixed low dose hydroxyurea (10 mg/kg) per day for six months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hydroxyurea<br>500mg of hydroxyurea/day during 6 months | Drug: hydroxyurea<br> <br> * Other names: Hydroxycarbamide;|
| No Intervention: No treatment<br>No hydroxyurea treatment during 6 months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytopenia | Neutrophil count <500/microliter, platelet count <50,000 or a reticulocyte count<95,000 with Hemoglobin of 9.0 g/dL | every 2 weeks during a period of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of infection evaluated by a physician at the point of care | Infections such as malaria or tuberculosis, which may be newly acquired or recrudescent. | every 2 weeks for period of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell anemia, sickle cell disease, hydroxyurea, Nigeria, low income country, middle income country, developing country