Intermittent Hypoxia and Caffeine in Infants Born Preterm

Summary

Intermittent Hypoxia and Caffeine in Infants Born Preterm (ICAF) Our proposal will address the critical question: is persisting intermittent hypoxia (IH) in preterm infants associated with biochemical, structural, or functional injury, and is this injury attenuated with extended caffeine treatment? The investigators will study the effects of caffeine on IH in 220 preterm infants born at ≤30 weeks + 6 days gestation. Infants who are currently being treated with routine caffeine, and who meet eligibility criteria, will be enrolled between 32 weeks + 0 days and 36 weeks + 6 days PMA. At enrollment, infants will be started on continuous pulse oximeter recording of O2 saturation and heart rate. If, based on standard clinical criteria, the last dose of routine caffeine is given on or before the day the infant is 36 weeks + 5 days PMA, then on the day following their last dose of routine caffeine treatment, infants will be randomized (110/group) to extended caffeine treatment or placebo. Randomized infants should begin receiving study drug (i.e. 5 mg/kg/of caffeine base, or equal volume of placebo) on the day of randomization, but no later than the third calendar day following the last dose of routine caffeine. Prior to 36 weeks + 0 days PMA, study drug will be given once daily (i.e. 5mg/kg/day) and beginning at 36 weeks + 0 days PMA, study drug will be given twice daily (i.e. 10 mg/kg/day). The last dose of study drug will be given at 42 weeks + 6 days PMA. Pulse oximeter recordings will continue 1 additional week after discontinuing study drug. Two caffeine levels will be obtained, the 1st at one week after beginning study drug, and the 2nd at a target date of 40 weeks + 0 days PMA, but no later than the last day of study drug, whether in hospital or at home. Inflammatory biomarkers will be measured at study enrollment and again at 38 weeks + 0 days PMA, or within 2 calendar days prior to hospital discharge, whichever comes first. Quantitative MRI/MRS should be obtained between study enrollment and 3 calendar days after starting study drug and again at a target date of 43 weeks + 0 days, but no later than 46 weeks + 6 days PMA.

Timeline

Start

2019-01-18

Primary completion

2023-06-01

Completion

2023-06-01

Publications

• Results Rhein LM, Dobson NR, Darnall RA, Corwin MJ, Heeren TC, Poets CF, McEntire BL, Hunt CE; Caffeine Pilot Study Group. Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial. JAMA Pediatr. 2014 Mar;168(3):250-7. doi: 10.1001/jamapediatrics.2013.4371.
• Results Dobson NR, Rhein LM, Darnall RA, Corwin MJ, Heeren TC, Eichenwald E, James LP, McEntire BL, Hunt CE; Caffeine Study Group. Caffeine decreases intermittent hypoxia in preterm infants nearing term-equivalent age. J Perinatol. 2017 Oct;37(10):1135-1140. doi: 10.1038/jp.2017.82. Epub 2017 Jul 27.
• Eichenwald E, Corwin M, McEntire B, Knoblach S, Limperopoulos C, Kapse K, Kerr S, Heeren TC, Ikponmwonba C, Hunt CE; ICAF Study Group. Intermittent hypoxia and caffeine in infants born preterm: the ICAF Randomized Clinical Trial. Arch Dis Child Fetal Neonatal Ed. 2026 Apr 17;111(3):F249-F255. doi: 10.1136/archdischild-2025-329230.
• Erickson G, McAnulty M, Powers C, Luong TL, Dobson NR, Hunt CE. Stability for 6 months and accuracy of a specific enteral caffeine base preparation for a multisite clinical trial. Br J Clin Pharmacol. 2023 Aug;89(8):2631-2635. doi: 10.1111/bcp.15739. Epub 2023 Apr 21.

Drugs

Indications

No indication recorded.