Novel Use of Hydroxyurea in an African Region With Malaria: Protocol for a Randomized Controlled Clinical Trial

Juliana N Anyanwu, Olatundun Williams, Casey L Sautter, Phillip Kasirye, Heather Hume, Robert O Opoka, Teresa Latham, Christopher Ndugwa, Russell E Ware, Chandy C John

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Sickle cell anemia (SCA), one of most prevalent monogenic diseases worldwide, is caused by a glutamic acid to valine substitution on the beta globin protein of hemoglobin, which leads to hemolytic anemia. Hydroxyurea, the only disease-modifying therapy approved by the Food and Drug Administration for SCA, has proven to be a viable therapeutic option for SCA patients in resource-rich settings, given clinical improvements experienced while taking the medication and its once-daily oral dosing. Significant studies have demonstrated its safety and clinical efficacy among children and adults in developed countries. In Sub-Saharan Africa, however, the risk of malaria, hematologic toxicities, and safety of hydroxyurea in children with SCA living in malaria-endemic areas are unknown.

OBJECTIVES: Study objectives include determining the incidence of malaria in SCA patients taking hydroxyurea versus placebo; establishing the frequency of hematologic toxicities and adverse events (AEs) in children with SCA treated with hydroxyurea versus placebo; and defining the relationships between hydroxyurea treatment and fetal hemoglobin, soluble intracellular adhesion molecule-1, and nitric oxide levels, and between levels of these factors and risk of subsequent malaria.

METHODS: Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM, NCT01976416) is a prospective, randomized, placebo-controlled, double-blinded phase III trial to compare risk of malaria with oral hydroxyurea versus placebo. Children will be recruited from the Mulago Hospital Sickle Cell Clinic in Kampala, Uganda.

RESULTS: Two hundred Ugandan children aged between 1.00 and 3.99 years with confirmed SCA will be randomized into treatment groups by order of entry in the study, based on a predetermined blinded randomization list. The primary outcome of the trial is malaria incidence in the 2 study groups, defined as episodes of clinical malaria occurring over the 1-year randomized study treatment period.

CONCLUSION: NOHARM will be the first prospective randomized, placebo-controlled clinical trial investigating the use of hydroxyurea for children with SCA in a malaria-endemic region within Africa. The results of this trial have the potential to significantly advance understanding of how to safely and effectively use hydroxyurea in children with SCA in malaria-endemic areas.

TRIAL REGISTRATION: Clinicaltrials.gov NCT01976416; https://clinicaltrials.gov/ct2/show/NCT01976416 (Archived by WebCite at http://www.webcitation.org/6hmoilZnp).

Original languageEnglish (US)
Pages (from-to)e110
JournalJMIR Res Protoc
Volume5
Issue number2
DOIs
StatePublished - Jun 23 2016

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    Anyanwu, J. N., Williams, O., Sautter, C. L., Kasirye, P., Hume, H., Opoka, R. O., Latham, T., Ndugwa, C., Ware, R. E., & John, C. C. (2016). Novel Use of Hydroxyurea in an African Region With Malaria: Protocol for a Randomized Controlled Clinical Trial. JMIR Res Protoc, 5(2), e110. https://doi.org/10.2196/resprot.5599