Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

Robert O. Opoka, Christopher M. Ndugwa, Teresa S. Latham, Adam Lane, Heather A. Hume, Phillip Kasirye, James S. Hodges, Russell E. Ware, Chandy John

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2585-2593
Number of pages9
JournalBlood
Volume130
Issue number24
DOIs
StatePublished - Dec 14 2017

Fingerprint

Hydroxyurea
Sickle Cell Anemia
Malaria
Placebos
Africa South of the Sahara
Toxicity
Incidence
Infection
Acute Chest Syndrome
Fetal Hemoglobin
Uganda
Reticulocytes
Hemoglobin
Therapeutics
Neutropenia
Blood Transfusion
Sepsis
Hemoglobins
Leukocytes
Blood

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM) : a trial for children with sickle cell anemia. / Opoka, Robert O.; Ndugwa, Christopher M.; Latham, Teresa S.; Lane, Adam; Hume, Heather A.; Kasirye, Phillip; Hodges, James S.; Ware, Russell E.; John, Chandy.

In: Blood, Vol. 130, No. 24, 14.12.2017, p. 2585-2593.

Research output: Contribution to journalArticle

Opoka, RO, Ndugwa, CM, Latham, TS, Lane, A, Hume, HA, Kasirye, P, Hodges, JS, Ware, RE & John, C 2017, 'Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia', Blood, vol. 130, no. 24, pp. 2585-2593. https://doi.org/10.1182/blood-2017-06-788935
Opoka, Robert O. ; Ndugwa, Christopher M. ; Latham, Teresa S. ; Lane, Adam ; Hume, Heather A. ; Kasirye, Phillip ; Hodges, James S. ; Ware, Russell E. ; John, Chandy. / Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM) : a trial for children with sickle cell anemia. In: Blood. 2017 ; Vol. 130, No. 24. pp. 2585-2593.
@article{34346553302142778b2948803b4d06ac,
title = "Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia",
abstract = "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.",
author = "Opoka, {Robert O.} and Ndugwa, {Christopher M.} and Latham, {Teresa S.} and Adam Lane and Hume, {Heather A.} and Phillip Kasirye and Hodges, {James S.} and Ware, {Russell E.} and Chandy John",
year = "2017",
month = "12",
day = "14",
doi = "10.1182/blood-2017-06-788935",
language = "English (US)",
volume = "130",
pages = "2585--2593",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "24",

}

TY - JOUR

T1 - Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM)

T2 - a trial for children with sickle cell anemia

AU - Opoka, Robert O.

AU - Ndugwa, Christopher M.

AU - Latham, Teresa S.

AU - Lane, Adam

AU - Hume, Heather A.

AU - Kasirye, Phillip

AU - Hodges, James S.

AU - Ware, Russell E.

AU - John, Chandy

PY - 2017/12/14

Y1 - 2017/12/14

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85038244157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038244157&partnerID=8YFLogxK

U2 - 10.1182/blood-2017-06-788935

DO - 10.1182/blood-2017-06-788935

M3 - Article

C2 - 29051184

AN - SCOPUS:85038244157

VL - 130

SP - 2585

EP - 2593

JO - Blood

JF - Blood

SN - 0006-4971

IS - 24

ER -