PMID- 29051184
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20220408
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 130
IP  - 24
DP  - 2017 Dec 14
TI  - Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for 
      children with sickle cell anemia.
PG  - 2585-2593
LID - 10.1182/blood-2017-06-788935 [doi]
AB  - Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) 
      living in high-resource malaria-free regions, but its safety and efficacy in 
      malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, 
      remain unknown. In vitro studies suggest hydroxyurea could increase malaria 
      severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM 
      (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, 
      double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, 
      comparing hydroxyurea to placebo at 20 +/- 2.5 mg/kg per day for 12 months. The 
      primary outcome was incidence of clinical malaria. Secondary outcomes included 
      SCA-related adverse events (AEs), clinical and laboratory effects, and 
      hematological toxicities. Children received either hydroxyurea (N = 104) or 
      placebo (N = 103). Malaria incidence did not differ between children on 
      hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 
      0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the 
      hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). 
      Time to infection also did not differ significantly between treatment arms. A 
      composite SCA-related clinical outcome (vaso-occlusive painful crisis, 
      dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) 
      was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children 
      receiving hydroxyurea had significantly increased hemoglobin concentration and 
      fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, 
      sepsis episodes, and dose-limiting toxicities were similar between treatment 
      arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). 
      Hydroxyurea treatment appears safe for children with SCA living in 
      malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, 
      or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but 
      optimal dosing and monitoring regimens for Africa remain undefined. This trial 
      was registered at www.clinicaltrials.gov as #NCT01976416.
CI  - (c) 2017 by The American Society of Hematology.
FAU - Opoka, Robert O
AU  - Opoka RO
AD  - Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda.
FAU - Ndugwa, Christopher M
AU  - Ndugwa CM
AD  - Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda.
FAU - Latham, Teresa S
AU  - Latham TS
AD  - Division of Hematology, Department of Pediatrics, Cincinnati Children's Hospital 
      Medical Center, Cincinnati, OH.
FAU - Lane, Adam
AU  - Lane A
AD  - Division of Hematology, Department of Pediatrics, Cincinnati Children's Hospital 
      Medical Center, Cincinnati, OH.
FAU - Hume, Heather A
AU  - Hume HA
AD  - Departement de Pediatrie, Universite de Montreal Service d'Hematologie/Oncologie, 
      Montreal, QC, Canada.
FAU - Kasirye, Phillip
AU  - Kasirye P
AD  - Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda.
FAU - Hodges, James S
AU  - Hodges JS
AD  - Division of Biostatistics, School of Public Health, University of Minnesota, 
      Minneapolis, MN; and.
FAU - Ware, Russell E
AU  - Ware RE
AUID- ORCID: 0000-0001-9582-0594
AD  - Division of Hematology, Department of Pediatrics, Cincinnati Children's Hospital 
      Medical Center, Cincinnati, OH.
FAU - John, Chandy C
AU  - John CC
AUID- ORCID: 0000-0002-1634-1411
AD  - Ryan White Center for Infectious Diseases and Global Health, Department of 
      Pediatrics, University of Indiana, Indianapolis, IN.
LA  - eng
SI  - ClinicalTrials.gov/NCT01976416
SI  - ClinicalTrials.gov/NCT01976416
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20171019
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antisickling Agents)
RN  - 9034-63-3 (Fetal Hemoglobin)
RN  - X6Q56QN5QC (Hydroxyurea)
SB  - IM
CIN - Blood. 2017 Dec 14;130(24):2575-2576. PMID: 29242203
MH  - Anemia, Sickle Cell/blood/*drug therapy/*epidemiology
MH  - Antisickling Agents/therapeutic use
MH  - Blood Cell Count
MH  - Child, Preschool
MH  - Double-Blind Method
MH  - Endemic Diseases
MH  - Female
MH  - Fetal Hemoglobin/metabolism
MH  - Humans
MH  - Hydroxyurea/*therapeutic use
MH  - Incidence
MH  - Infant
MH  - Malaria/*epidemiology
MH  - Male
MH  - Prospective Studies
MH  - Treatment Outcome
MH  - Uganda/epidemiology
EDAT- 2017/10/21 06:00
MHDA- 2017/12/28 06:00
CRDT- 2017/10/21 06:00
PHST- 2017/06/03 00:00 [received]
PHST- 2017/08/18 00:00 [accepted]
PHST- 2017/10/21 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
PHST- 2017/10/21 06:00 [entrez]
AID - S0006-4971(20)32638-0 [pii]
AID - 10.1182/blood-2017-06-788935 [doi]
PST - ppublish
SO  - Blood. 2017 Dec 14;130(24):2585-2593. doi: 10.1182/blood-2017-06-788935. Epub 
      2017 Oct 19.