Sickle Cell DiseasePhase 4NCT02149537
Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment
A Phase 4 study testing hydroxyurea in people with Sickle Cell Disease and Sickle Cell Anemia, run by Loyola University at 1 site in Nigeria.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell Anemia
- What is being tested?
- hydroxyurea
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteNigeria
- Study dates
- Dec 2014to Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- HIVpositive
- Hepatitis B and/or C positive
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Sickle Cell Disease, Sickle Cell Anemia
- Being tested
- hydroxyurea
- Keywords
- sickle cell disease, sickle cell anemia, hydroxyurea, Nigeria, low income country, middle income country, developing country
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydroxyureaDrug
Also called Hydroxycarbamide
| Study group | Role | What they receive |
|---|---|---|
| hydroxyurea | Experimental | 500mg of hydroxyurea/day during 6 months Receives: Drug: hydroxyurea |
| No treatment | No intervention | No hydroxyurea treatment during 6 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytopenia
Neutrophil count <500/microliter, platelet count <50,000 or a reticulocyte count<95,000 with Hemoglobin of 9.0 g/dL
Measured: every 2 weeks during a period of 6 months
Secondary outcomes (1)
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.
Measured: every 2 weeks for period of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2014 (estimated)
- Study startDec 2014
- Primary completionSep 2017
- Study completionDec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- 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)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Illinois Chicago, University of Ibadan
- Responsible party
- Principal investigator, Bamidele Tayo, Loyola University
- Investigators
- Bamidele O Tayo, PhD, Principal investigator, Loyola University ChicagoVictor R Gordeuk, MD, Principal investigator, University of Illinois ChicagoTitilola S Akingbola, MBBS, FWACP, Principal investigator, University of Ibadan College of Medicine, NigeriaRichard S Cooper, MD, Principal investigator, Loyola University ChicagoLewis Hsu, MD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02149537
- Sponsor's protocol ID
- 205449
- Status last verified
- Mar 2023
- First submitted
- 24 Mar 2014
- Last updated
- 9 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
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.
PubMed 28868518Tayo 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.
PubMed 29756251Akingbola 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.
PubMed 30663794
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea
- ClinicalTrials.gov ID
- NCT02149537
- Acronym / sponsor ID
- 205449
- Conditions
- Sickle Cell Disease, Sickle Cell Anemia
- Keywords
- sickle cell disease, sickle cell anemia, hydroxyurea, Nigeria, low income country, middle income country, developing country
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Collaborators
- University of Illinois Chicago, University of Ibadan
- Study start
- Dec 2014
- Primary completion
- Sep 2017 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 29 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| hydroxyurea | Experimental | Drug: hydroxyurea500mg of hydroxyurea/day during 6 months |
| No treatment | No intervention | –No hydroxyurea treatment during 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (2 listed)
- HIVpositive
- Hepatitis B and/or C positive
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydroxyureaAlso: Hydroxycarbamide | Drug | hydroxyurea |
Primary outcome
Cytopenia
Time frame: every 2 weeks during a period of 6 months
Neutrophil count <500/microliter, platelet count <50,000 or a reticulocyte count<95,000 with Hemoglobin of 9.0 g/dL
1 secondary outcome
Development of infection evaluated by a physician at the point of care
Time frame: every 2 weeks for period of 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2023.
- Background: PubMed 28868518Saraf 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.
- Results publication: PubMed 29756251Tayo 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.
- Results publication: PubMed 30663794Akingbola 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bamidele O Tayo, PhD principal investigator
Loyola University Chicago
Victor R Gordeuk, MD principal investigator
University of Illinois Chicago
Titilola S Akingbola, MBBS, FWACP principal investigator
University of Ibadan College of Medicine, Nigeria
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing hydroxyurea in people with Sickle Cell Disease and Sickle Cell Anemia, run by Loyola University at 1 site in Nigeria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytopenia (time frame: every 2 weeks during a period of 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02149537, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2023.