Extended Caffeine for Apnea in Moderately Preterm Infants

Hospitalization of moderately preterm infants may be prolonged while waiting for apnea of prematurity to resolve after discontinuing caffeine. To evaluate whether extending caffeine treatment reduces the duration of hospitalization. From February 2019 to December 2022, this randomized clinical trial in 29 US hospitals enrolled infants born at 29 to 33 weeks' gestation who at 33 to 35 weeks' postmenstrual age were receiving caffeine treatment with plans to discontinue it plus receiving full feeds (≥120 mL/kg/d). Follow-up was completed on March 20, 2023. Infants were randomized to oral caffeine citrate (10 mg/kg/d) or placebo until 28 days after discharge. The primary outcome was days to discharge after randomization. Secondary outcomes included days to physiological maturity (apnea free for 5 consecutive days, receiving full oral feeds, and out of the incubator for at least 48 hours), postmenstrual age at discharge, all-cause hospital readmissions, all-cause sick and emergency department visits, safety outcomes, and death. A total of 827 infants (median gestational age, 31 weeks; 414 female [51%]) were randomized (416, caffeine; 411, placebo) out of the 878 planned before reaching the prespecified futility threshold. Days of hospitalization after randomization did not differ between groups (18.0 days [IQR, 10 to 30 days] for caffeine vs 16.5 [IQR, 10 to 27 days] for placebo; adjusted median difference, 0 days [95% CI, -1.7 to 1.7 days]), nor did days to physiological maturity differ (14.0 vs 15.0 days, adjusted median difference, -1 day [95% CI, -2.4 to 0.4 days]). Infants receiving caffeine were apnea free sooner (6.0 vs 10.0 days; adjusted median difference, -2.7 days [95% CI, -3.4 to -2.0 days ]) but had similar days to full oral feeding (7.5 vs 6.0 days, adjusted median difference, 0 days [95% CI, -0.1 to 0.1]). Rates of readmissions and sick visits did not differ between groups. There was no statistically significant difference in adverse events between the 2 groups. In moderately preterm infants, continuation of caffeine treatment compared with placebo did not shorten hospitalization. ClinicalTrials.gov Identifier: NCT03340727.