Novel Use of Hydroxyurea in an African Region With Malaria
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Date
2016
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
JMIR research protocols
Abstract
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)
Description
Keywords
Sickle cell anemia, Hydroxyurea, Malaria
Citation
Anyanwu, J. N., Williams, O., Sautter, C. L., Kasirye, P., Hume, H., Opoka, R. O., ... & John, C. C. (2016). Novel use of hydroxyurea in an African region with malaria: protocol for a randomized controlled clinical trial. JMIR research protocols, 5(2), e5599.