Oral D-penicillamine for the prevention of retinopathy of prematurity in very low birth weight infants: a randomized, placebo-controlled trial

Abstract

Purpose: To compare prophylactic enteral D-penicillamine (DPA) with placebo for prevention of 'retinopathy of prematurity (ROP) or death' among very low birth weight (VLBW) infants.

Methods: This was a double-blind, single-centre, randomized, placebo-controlled trial with stratification (for birth weight <1250 and ≥1250 g) and blocking. Inborn neonates with birth weight 750-1500 g, gestation ≤32 weeks, age ≤5 days, who tolerated feeds were eligible. Neonates with gastro-intestinal malformations, life-threatening malformations and necrotizing enterocolitis were excluded. Enrolled subjects were randomly allocated to receive oral DPA suspension at 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg/day for another 11 days or placebo. The primary outcome was 'any ROP or death'. Secondary outcomes included any ROP, treatable ROP, adverse effects and feed intolerance.

Results: A total of 88 subjects were enrolled. Baseline characteristics were similar with the exception of multiple gestation. There were no significant differences in primary and secondary outcomes, even after adjusting for multiple gestation and on sub-group analysis. No adverse reaction was noted.

Conclusion: Prophylactic enterally administered DPA suspension in a dose 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg once per day for next 11 days, does not prevent 'any stage ROP or death' or 'ROP requiring treatment' in VLBW infants. DPA is well tolerated and does not have any major short-term adverse effects.