Clinical trial NCT02149537: Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment
Official title: Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sickle Cell Disease
Sickle Cell Anemia
Keywords: sickle cell disease
sickle cell anemia
hydroxyurea
Nigeria
low income country
middle income country
developing country
Lead sponsor: Loyola University
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
name: University of Ibadan
First posted: 2014-05-29
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cytopenia
timeFrame: every 2 weeks during a period of 6 months
Secondary outcomes:
measure: Development of infection evaluated by a physician at the point of care
timeFrame: every 2 weeks for period of 6 months
Other outcomes:
measure: laboratory values of Hemoglobin F%, hemoglobin concentration, reticulocyte count, mean corpuscular volume and white blood cell count.
timeFrame: baseline, 3 months and 6 months.
measure: Clinical complications such as acute pain episode, acute chest syndrome and need for blood transfusion.
timeFrame: every 2 weeks for a period of 6 months.
Locations:
city: Ibadan
country: Nigeria
facility: University of Ibadan College of Medicine
state: Oyo State
Study officials:
affiliation: Loyola University Chicago
name: Bamidele O Tayo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois at Chicago
name: Victor R Gordeuk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ibadan College of Medicine, Nigeria
name: Titilola S Akingbola, MBBS, FWACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Loyola University Chicago
name: Richard S Cooper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois at Chicago
name: Lewis Hsu, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. Online ahead of print. No abstract available.
citation: 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.