BABY HUG

Background

Phase III double-blind placebo-controlled RCT. 193 infants aged 9–18 months (mean 13.6 months) with SCD (HbSS or HbSβ0) regardless of disease severity. Patients with TCD ≥200 cm/s were eligible for the parallel transfusion protocol. Stratified by hemoglobin type and site. Designed to test whether early hydroxyurea initiation could prevent organ dysfunction in the youngest SCD patients before permanent damage occurs. First randomized trial of hydroxyurea in this age group.

Interventions and follow up

Arm A: Hydroxyurea 20 mg/kg/day orally
Arm B: Placebo
Primary endpoint: Urine osmolality (renal function) and spleen function score (isotopic scan) at 2 year
mFollow up: 24 month

Results

Spleen function score: No significant difference (P=.89)
Urine osmolality: No significant difference (primary endpoints not met)
Pain/dactylitis events: 4% (HU) vs 24% (placebo), P=.002
ACS rate: 7% vs 23%, P=.004
Hospitalizations: 122 vs 222 events (HU vs placebo)
Transfusion requirement: 24% (HU) vs 48% (placebo)

Adverse events

Main adverse events: Mild neutropenia in HU group (median ANC 4.03 vs 4.30 ×10³/µL). No increase in serious infections. Overall serious AE rates similar between groups. Hydroxyurea was well tolerated in infants, with no unexpected toxicities.

Conclusions

Hydroxyurea did not preserve splenic or renal function in infants with SCD (primary endpoints not met), but substantially reduced clinical events including pain episodes, ACS, hospitalizations, and transfusion requirements, supporting early HU initiation for clinical benefit.

Key Limitations

Key Limitations: Primary endpoints (urine osmolality, spleen function score) were surrogate markers without proven clinical relevance. Sample size was underpowered for detecting functional organ differences. Pre-existing organ damage at 9–18 months may not be reversible by HU alone. No long-term neurocognitive or stroke endpoints. Short 2-year follow-up. Organ protective effects may require earlier initiation (pre-natal) or longer treatment.

Clinical Context

Though primary endpoints were not met, BABY HUG established that hydroxyurea is safe and clinically beneficial in infants ≥9 months. This contributed to ASH 2020 SCD guidelines recommending offering hydroxyurea to all SCD patients ≥9 months regardless of disease severity. Current standard of care is early HU initiation. Dosing in infants starts at 20 mg/kg/day. Hydroxyurea increases HbF and reduces sickling, with real-world pediatric data supporting benefit across SCD genotypes.

References

References: Wang WC et al, Lancet 2011 (BABY HUG primary)