PMID- 27339303
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160624
LR  - 20200930
IS  - 1929-0748 (Print)
IS  - 1929-0748 (Electronic)
IS  - 1929-0748 (Linking)
VI  - 5
IP  - 2
DP  - 2016 Jun 23
TI  - Novel Use of Hydroxyurea in an African Region With Malaria: Protocol for a 
      Randomized Controlled Clinical Trial.
PG  - e110
LID - 10.2196/resprot.5599 [doi]
LID - e110
AB  - 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).
FAU - Anyanwu, Juliana N
AU  - Anyanwu JN
AUID- ORCID: 0000-0002-4271-7910
AD  - University of Minnesota, Minneapolis, MN, United States.
FAU - Williams, Olatundun
AU  - Williams O
AUID- ORCID: 0000-0003-2163-3918
FAU - Sautter, Casey L
AU  - Sautter CL
AUID- ORCID: 0000-0001-9727-4953
FAU - Kasirye, Phillip
AU  - Kasirye P
AUID- ORCID: 0000-0001-6620-483X
FAU - Hume, Heather
AU  - Hume H
AUID- ORCID: 0000-0002-4171-104X
FAU - Opoka, Robert O
AU  - Opoka RO
AUID- ORCID: 0000-0003-3240-2058
FAU - Latham, Teresa
AU  - Latham T
AUID- ORCID: 0000-0002-4473-5821
FAU - Ndugwa, Christopher
AU  - Ndugwa C
AUID- ORCID: 0000-0002-3244-551X
FAU - Ware, Russell E
AU  - Ware RE
AUID- ORCID: 0000-0001-9582-0594
FAU - John, Chandy C
AU  - John CC
AUID- ORCID: 0000-0002-1634-1411
LA  - eng
SI  - ClinicalTrials.gov/NCT01976416
GR  - R25 TW009345/TW/FIC NIH HHS/United States
PT  - Journal Article
DEP - 20160623
PL  - Canada
TA  - JMIR Res Protoc
JT  - JMIR research protocols
JID - 101599504
PMC - PMC4937184
OTO - NOTNLM
OT  - hydroxyurea
OT  - malaria
OT  - sickle cell anemia
COIS- Conflicts of Interest: None declared.
EDAT- 2016/06/25 06:00
MHDA- 2016/06/25 06:01
PMCR- 2016/06/23
CRDT- 2016/06/25 06:00
PHST- 2016/02/03 00:00 [received]
PHST- 2016/04/03 00:00 [accepted]
PHST- 2016/06/25 06:00 [entrez]
PHST- 2016/06/25 06:00 [pubmed]
PHST- 2016/06/25 06:01 [medline]
PHST- 2016/06/23 00:00 [pmc-release]
AID - v5i2e110 [pii]
AID - 10.2196/resprot.5599 [doi]
PST - epublish
SO  - JMIR Res Protoc. 2016 Jun 23;5(2):e110. doi: 10.2196/resprot.5599.