Objective: This is the first multicenter, double blind, placebo controlled study with an open-label rescue phase (OLRP) to evaluate the efficacy of CC in the preterm infant 28 to 32 weeks post conceptual age with AOP.

Method: 82 infants with ≥6 apnea episodes >20 sec. per 24 hours were randomized to receive PL (N=37) or CC (N=45); IV loading dose of 10 mg/kg with daily dose of 2.5 mg/kg caffeine base or an equivalent volume of placebo. Success was defined as ≥50% reduction in apneic episodes during 24 to 48 hrs after loading dose. Double blind phase lasted up to 10 days. Infants defined as failure were withdrawn or enrolled in OLRP, receiving another loading dose of 10 mg/kg followed by 3mg/kg daily caffeine base.

Results: The mean gestational age and weight at birth and post conceptual age at study entry were not significantly different between the two groups. The percent success rate was greater for CC than PL for all 10 study days. Cumulative number of days with ≥50% decrease in apneic episodes was 68.9% for infants receiving CC vs. 43.2% for PL (p=0.0195). Percent of infants with 7 to 10 days of no apneic episodes was 24.4% for CC vs. 0.0% for PL(p=0.005). AOP elimination did not correlate with the mean CC plasma level. Infants in the OLRP who had originally received PL generally responded better that the infants who originally received CC, but the responses were not significantly different. Of the parameters studied, it was not possible to identify which infant with AOP would not benefit from CC. There were no significant differences in adverse events between the two groups.

Conclusions: 1. In the 28 to 32 wk post conceptual age infant, AOP does respond to CC with a significant decrease in apneic episodes. 2. Although not all infants with AOP may require CC, it is currently not possible to clinically separate them from the infant benefiting from CC therapy.