Comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity in preterm (≤34 weeks) neonates: A randomized controlled trial

Objective: To compare the efficacy and safety of standard doses of Caffeine and Aminophylline for Apnea of prematurity. Study design: Randomized controlled trial. Setting: Tertiary-care referral centre and a teaching institution in Southern India. Trial was conducted from February 2012 to January 2015. Participants: 240 preterm (≤34 wk) neonates with apnea of prematurity. Interventions: Neonates randomized into two groups: Caffeine group received loading dose of caffeine citrate (20 mg/kg) followed by 5 mg/kg/day maintenance dose every 24 hour. Aminophylline group received loading dose of Aminophylline–5 mg/kg and maintenance dose of 1.5 mg/kg 8-hourly. Outcome measures: Difference in apneic spells, associated respiratory morbidity, and acute adverse events were assessed. Association of efficacy with therapeutic drug levels was also evaluated. Results: Infants on aminophylline experienced less apnea spells in 4-7 days of therapy (P=0.03). Mean apnea rate and isolated desaturations were similar in 1-3, 4-7 and 8-14 days of therapy. No difference was noted in duration of Neonatal Intensive Care Unit stay and hospital stay. Mean heart rate was significantly high in Aminophylline group (P<0.001). Risk of developing tachycardia was less (RR 0.30; 95% CI range 0.15 to 0.60; P<0.001) in Caffeine- over Aminophylline-treated infants. Conclusion: Aminophylline is as effective as caffeine for prevention of apneic spells in preterm neonates; however, dosage optimization needs to be done to reduce toxicity.