Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study.

STUDY OBJECTIVE To evaluate the efficacy and safety of caffeine citrate for treatment of apnea of prematurity. DESIGN Multicenter, parallel, randomized, double-blind, placebo-controlled trial with open-label rescue. SETTING Nine neonatal intensive care units. PATIENTS Eighty-five infants, 28-32 weeks postconception and 24 hours or more after birth who had six or more apnea episodes within 24 hours. INTERVENTION Caffeine citrate 10 mg/kg (as caffeine base) administered intravenously, followed by 2.5 mg/kg/day orally or intravenously, or placebo, for up to 10 days. Infants failing double-blind therapy could receive open-label rescue. MEASUREMENTS AND MAIN RESULTS Success was defined as 50% or greater reduction in apnea episodes and elimination of apnea. Caffeine citrate was significantly more effective than placebo in reducing apnea episodes by at least 50% in 6 days (p<0.05), and approached statistical significance (p<0.10) in 3 days. It was significantly better than placebo in eliminating apnea in 5 days (p<0.05), and approached significance (p<0.10) in 2 days. The number of infants with an aggregate of 7-10 days of at least a 50% reduction in apnea events or elimination of apnea was significantly higher in the caffeine citrate than in the placebo group. Adverse events did not differ significantly between groups. No correlations were found between success and mean daily plasma concentrations or baseline characteristics. Volume of distribution and clearance increased with weight, supporting weight-adjusted dosing of caffeine citrate. CONCLUSION Caffeine citrate 10 mg/kg caffeine base (equivalent to 20 mg/kg caffeine citrate) intravenously followed by 2.5 mg/kg/day caffeine base (equivalent to 5 mg/kg/day caffeine citrate) either intravenously or orally for 10 days is safe and effective for treating apnea of prematurity in infants 28-32 weeks postconception.