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

Loyola University

Status and phase: Completed; Phase 4

Conditions: Sickle Cell Anemia; Sickle Cell Disease

Treatments: Drug: hydroxyurea

Study type: Interventional

Funder types: Other

Identifiers

NCT02149537

205449

Details and patient eligibility

About

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.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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53 participants in 2 patient groups

hydroxyurea

Experimental group

Description:

500mg of hydroxyurea/day during 6 months

Treatment:

Drug: hydroxyurea

No treatment

No Intervention group

Description:

No hydroxyurea treatment during 6 months