Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
Open accessAbstract
Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA.
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In contrast, all children seem to have a robust HbF response to hydroxyurea that retards the natural age-related fall in HbF.
“In contrast, all children seem to have a robust HbF response to hydroxyurea that retards the natural age-related fall in HbF.87”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [87]
The Results (Organ Function; page not provided) report that HbF remained relatively stable in the hydroxyurea group while it declined with age in the placebo group, with a 5.3% higher mean HbF at exit. These are group-level findings in very young children; they do not establish a robust response in every child or in children of all ages. (LLM, conf=0.88)
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- Authors
- Wang, W. C., Ware, R. E., Miller, S. T., Iyer, R. V., Casella, J. F., Minniti, C. P., Rana, S., Thornburg, C. D., Rogers, Z. R., Kalpatthi, R. V., Barredo, J. C., Brown, R. C., Sarnaik, S. A., Howard, T. H., Wynn, L. W., Kutlar, A., Armstrong, F. D., Files, B. A., Goldsmith, J. C., Waclawiw, M. A., Huang, X., & Thompson, B. W.
- Affiliations
- St. Jude Children's Research Hospital (US)
- SUNY Downstate Health Sciences University (US)
- University of Mississippi Medical Center (US)
- Johns Hopkins University (US)
- Children's National (US)
- Howard University (US)
- Duke Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Medical University of South Carolina (US)
- University of Miami (US)
- Children's Hospital of Michigan (US)
- University of Alabama at Birmingham (US)
- Augusta University (US)
- Emory University (US)
- National Heart, Lung, and Blood Institute (US)
- Clinical Trials and Surveys Corporation (US)
- Corresponding author
- Wang, Winfred C
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 377
- Issue
- 9778
- Pages
- 1663-1672
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC3133619
- OpenAlex
- W2170086069
- Semantic Scholar
- 007f7341f1586c3f34ecd96fa415bd95116f1c85
- Cited by
- 803
- References
- 35
- Citations by year
- 2026: 46 · 2025: 42 · 2024: 57 · 2023: 49 · 2022: 58 · 2021: 54 · 2020: 58 · 2019: 67 · 2018: 50 · 2017: 64 · 2016: 52 · 2015: 61 · 2014: 50 · 2013: 45 · 2012: 25
- FWCI
- 21.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hb07156-19-0-1, n01hb07159-25-0-1, n01hb07153-18-0-1, n01hb07155-16-0-0, n01hb07158-17-0-0, n01hb07157-15-0-0, n01hb07152-18-0-0, n01hb07151-17-0-0, n01hb07150-20-0-1, n01hb07160-38-0-1, n01hb07154-21-0-0)
- National Heart, Lung, and Blood Institute (N01-HB-07154, N01-HB-07157, N01-HB-07160, N01 HB007155, N01-HB07155, N01-HB-07152, N01-HB-07153, N01 HB007150, N01-HB-07151, N01-HB-07158, N01-HB-07150, N01 HB007160, N01-HB-07159, N01-HB-07156)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- hydroxyurea, sickle cell disease, infants, spleen function, renal function, acute chest syndrome, pain episodes, fetal hemoglobin, brain development, mutagenicity, drug toxicity, beta-thalassemia, organ dysfunction, growth, transcranial Doppler, glomerular filtration rate, urine osmolality
- MeSH terms
- Anemia, Sickle Cell, Antisickling Agents, Blood Cell Count, Child Development, Female, Glomerular Filtration Rate, Hemoglobins, Humans, Hydroxyurea, Infant, Male, Osmolar Concentration, Pain, Spleen, United States, Urine, Biomarkers, Technetium Tc 99m Pentetate, Treatment Outcome, Ultrasonography, Doppler, Transcranial, Acute Chest Syndrome
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