- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02149537
Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment
March 7, 2023 updated by: Bamidele Tayo, Loyola University
Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
53
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Oyo State
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Ibadan, Oyo State, Nigeria
- University of Ibadan College of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: hydroxyurea
500mg of hydroxyurea/day during 6 months
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Other Names:
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No Intervention: No treatment
No hydroxyurea treatment during 6 months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cytopenia
Time Frame: every 2 weeks during a period of 6 months
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Neutrophil count <500/microliter, platelet count <50,000 or a reticulocyte count<95,000 with Hemoglobin of 9.0 g/dL
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every 2 weeks during a period of 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Development of infection evaluated by a physician at the point of care
Time Frame: every 2 weeks for period of 6 months
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Infections such as malaria or tuberculosis, which may be newly acquired or recrudescent.
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every 2 weeks for period of 6 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
laboratory values of Hemoglobin F%, hemoglobin concentration, reticulocyte count, mean corpuscular volume and white blood cell count.
Time Frame: baseline, 3 months and 6 months.
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baseline, 3 months and 6 months.
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Clinical complications such as acute pain episode, acute chest syndrome and need for blood transfusion.
Time Frame: every 2 weeks for a period of 6 months.
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Evaluated by a nurse or physician at point of care.
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every 2 weeks for a period of 6 months.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Bamidele O Tayo, PhD, Loyola University Chicago
- Principal Investigator: Victor R Gordeuk, MD, University of Illinois at Chicago
- Principal Investigator: Titilola S Akingbola, MBBS, FWACP, University of Ibadan College of Medicine, Nigeria
- Principal Investigator: Richard S Cooper, MD, Loyola University Chicago
- Principal Investigator: Lewis Hsu, MD, University of Illinois at Chicago
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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. Online ahead of print. No abstract available.
- 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-E115. doi: 10.1002/ajh.25412. Epub 2019 Feb 6. No abstract available.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2014
Primary Completion (Actual)
September 1, 2017
Study Completion (Actual)
December 1, 2022
Study Registration Dates
First Submitted
March 24, 2014
First Submitted That Met QC Criteria
May 28, 2014
First Posted (Estimate)
May 29, 2014
Study Record Updates
Last Update Posted (Estimate)
March 9, 2023
Last Update Submitted That Met QC Criteria
March 7, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 205449
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Study Data/Documents
-
Individual Participant Data Set
Information identifier: PR00007593Information comments: De-identified and anonymized IPD can be requested at http://doi.org/10.25934/PR00007593
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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