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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02149537
• Other study ID #: 205449
• Status: Completed
• Phase: Phase 4
• Start date: December 2014
• Est. completion date: December 2022

Study information

• Verified date: March 2023
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2022
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Anemia
• Sickle Cell Disease

Intervention

Drug:
• hydroxyurea

Locations

Country	Name	City	State
Nigeria	University of Ibadan College of Medicine	Ibadan	Oyo State

Sponsors (3)

Lead Sponsor	Collaborator
Loyola University	University of Ibadan, University of Illinois at Chicago

Country where clinical trial is conducted

Nigeria, 

References & Publications (3)

Akingbola TS, Tayo BO, Ezekekwu CA, Sonubi O, Zhang X, Saraf SL, Molokie R, Hsu LL, Han J, Cooper RS, Gordeuk VR. "Maximum tolerated dose" vs "fixed low-dose" hydroxyurea for treatment of adults with sickle cell anemia. Am J Hematol. 2019 Apr;94(4):E112-E — View Citation

Saraf SL, Akingbola TS, Shah BN, Ezekekwu CA, Sonubi O, Zhang X, Hsu LL, Gladwin MT, Machado RF, Cooper RS, Gordeuk VR, Tayo BO. Associations of alpha-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts. Blood Adv. 2017 Apr 25;1(11):693-698. doi: 10.1182/bloodadvances.2017005231. — View Citation

Tayo BO, Akingbola TS, Saraf SL, Shah BN, Ezekekwu CA, Sonubi O, Hsu LL, Cooper RS, Gordeuk VR. Fixed Low-Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Anemia in Nigeria. Am J Hematol. 2018 May 14:10.1002/ajh.25143. doi: 10.1002/ajh.25143. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	laboratory values of Hemoglobin F%, hemoglobin concentration, reticulocyte count, mean corpuscular volume and white blood cell count.		baseline, 3 months and 6 months.
Other	Clinical complications such as acute pain episode, acute chest syndrome and need for blood transfusion.	Evaluated by a nurse or physician at point of care.	every 2 weeks for a period of 6 months.
Primary	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	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