The authors of a study published in the Lancet suggest that “hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia”.

The randomised, controlled study was conducted across 13 centres in the United States. Trial participants were recruited between October 2003 and September 2007 and were aged between 9 to 18 months old (mean age 13.6 months). Eligible infants had haemoglobin SS or Sβ0thalassaemia, and were enrolled irrespective of clinical severity. They were randomised in a 1:1 ratio to either liquid hydroxycarbamide (previously known as hydroxyurea), 20 mg/kg per day (n = 96), or placebo (n = 97) for 2 years. Of the 193 infants randomised, 187 had HbSS and 6 had Sβ0thalassaemia (n=6), Active drug and placebo were formulated to have the same appearance and taste. The primary endpoint measures considered for this study were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate [GFR] by 99mTc-DTPA clearance). Further assessments included blood counts, foetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Infants were monitored every 2 weeks for adverse events (such as pain and dactylitis) and laboratory toxic effects until a tolerable dose was confirmed, and then every 4 weeks.

The trial authors note that a temporary administrative clinical hold on all study activity occurred from March to June, 2006, because of a specified expiration date on a batch of treatment packs. Overall, 179 (93%) participants who completed at least 18 months of the trial and at least one exit assessment were analysed; 167 (86%) completed the full study -  83 patients in the hydroxycarbamide group and 84 in the placebo group. The results found (from source):

• Significant differences were not seen between groups for the primary endpoints: Qualitative spleen scans were worse at exit than at entry in 19/70 (27%) of those on hydroxycarbamide and 28/74 (38%) of those receiving placebo (difference 11%, 95% CI −26 to 5, p=0.21). GFR, measured by 99mTc-DTPA clearance, did not differ in the two groups (difference 2 mL/min per 1.73m2, −16 to 20, p=0.84).

• Quantitative measures of spleen function (Howell-Jolly bodies, pit counts, and ratio of spleen to liver count) suggested benefit from hydroxycarbamide when the authors compared exit versus entry differences between the hydroxycarbamide and placebo groups (secondary endpoint measures)

• 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 foetal haemoglobin, and decreased white blood-cell count.

• Toxicity was limited to mild-to-moderate neutropenia.

The authors write, “Hydroxycarbamide was safe and resulted in a decrease in common but serious adverse events, especially pain and dactylitis, as well as improved laboratory parameters. Several secondary measures of spleen, kidney, and CNS function suggested benefit, but these results were not conclusive.” They go onto to conclude, “Our study is the only double-blind prospective paediatric trial to investigate the effect of hydroxycarbamide in very young children with sickle-cell anaemia. Patients in our trial differed from those in other trials in two important ways: they were very young, and eligible irrespective of whether they had severe clinical course of disease. On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all children with sickle-cell anaemia, starting at an early age.”

A related Comment article discusses the results of this study.

Speaking to BBC News, a consultant paediatric haematologist and medical adviser to the Sickle Cell Society, said that while the results of the study were "encouraging" that the drug was safe in very young children" the study was "in a way disappointing".
He said the primary aims of the study had been to show an impact on spleen or kidney function as "it had been hoped that if you can intervene early you could prevent organ damage", yet this was not the case.

The study is continuing until 2016 to enable long-term follow up data on efficacy and safety to be collected.