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Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG).
- Source :
-
Lancet (London, England) [Lancet] 2011 May 14; Vol. 377 (9778), pp. 1663-72. - Publication Year :
- 2011
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Abstract
- Background: Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects.<br />Methods: This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on (99)Tc spleen scan) and renal function (glomerular filtration rate by (99m)Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400.<br />Findings: 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m(2), p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia.<br />Interpretation: On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia.<br />Funding: The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Acute Chest Syndrome etiology
Acute Chest Syndrome prevention & control
Anemia, Sickle Cell complications
Anemia, Sickle Cell metabolism
Anemia, Sickle Cell pathology
Antisickling Agents adverse effects
Biomarkers blood
Blood Cell Count
Child Development
Female
Glomerular Filtration Rate
Hemoglobins metabolism
Humans
Hydroxyurea adverse effects
Infant
Male
Osmolar Concentration
Pain etiology
Pain prevention & control
Spleen pathology
Spleen physiopathology
Technetium Tc 99m Pentetate metabolism
Treatment Outcome
Ultrasonography, Doppler, Transcranial
United States
Urine chemistry
Anemia, Sickle Cell drug therapy
Anemia, Sickle Cell physiopathology
Antisickling Agents therapeutic use
Hydroxyurea therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1474-547X
- Volume :
- 377
- Issue :
- 9778
- Database :
- MEDLINE
- Journal :
- Lancet (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 21571150
- Full Text :
- https://doi.org/10.1016/S0140-6736(11)60355-3