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

NCT02149537 | Completed Phase 4 DMC

• 1 other identifier: 205449
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Keywords

sickle cell disease; sickle cell anemia; hydroxyurea; Nigeria; low income country; middle income country; developing country

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Development of infection evaluated by a physician at the point of care

  every 2 weeks for period of 6 months

Other Outcomes (2)

• laboratory values of Hemoglobin F%, hemoglobin concentration, reticulocyte count, mean corpuscular volume and white blood cell count.

  baseline, 3 months and 6 months.

• Clinical complications such as acute pain episode, acute chest syndrome and need for blood transfusion.

  every 2 weeks for a period of 6 months.

Study Arms (2)

hydroxyurea

EXPERIMENTAL

500mg of hydroxyurea/day during 6 months

Drug: hydroxyurea

No treatment

NO INTERVENTION

No hydroxyurea treatment during 6 months

Interventions

hydroxyurea DRUG

Also known as: Hydroxycarbamide

hydroxyurea

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• HIVpositive
• Hepatitis B and/or C positive

Sponsors & Collaborators

• Loyola University: lead
• University of Illinois at Chicago: collaborator
• University of Ibadan: collaborator

Study Sites (1)

University of Ibadan College of Medicine

Ibadan, Oyo State, Nigeria

Location

Related Publications (3)

• 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.

  PMID: 28868518 BACKGROUND

• 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.

  PMID: 29756251 RESULT

• 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.

  PMID: 30663794 RESULT

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant profesor

Model Details: 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.

Study Record Dates

• First Submitted: March 24, 2014
• First Posted: May 29, 2014
• Study Start: December 1, 2014
• Primary Completion: September 1, 2017
• Study Completion: December 1, 2022
• Last Updated: March 9, 2023

Record last verified: 2023-03

Locations

NG (1)