NCT03321734.

Study name	Intermittent hypoxia and caffeine in infants born preterm
Methods	Randomized, placebo‐controlled, double‐blinded clinical trial
Participants	Inclusion criteria: Male and female infants born preterm at ≤ 30 weeks + 6 days postmenstrual age (PMA) Current treatment with routine caffeine PMA 32 weeks + 0 days to 36 weeks + 6 days Anticipated last dose of routine caffeine will be by 36 weeks + 5 days At least 12 hours of breathing room air with no ventilatory support other than room air nasal air flow therapy regardless of flow rate, or on room air and receiving nasal CPAP, and relapse not anticipated Able to tolerate enteral medications It is feasible to administer the first dose of study drug no later than 36 weeks + 6 days PMA Exclusion Criteria: Intraventricular hemorrhage grade III to IV or cystic periventricular leukomalacia Current or prior treatment for seizures Current or prior treatment for cardiac arrhythmias Known renal or hepatic dysfunction, that in the opinion of the investigator, would have a clinically relevant impact on caffeine metabolism Major malformation, inborn error of metabolism, chromosomal abnormality Presence of a condition for which survival to discharge unlikely Social, mental health, logistical or other issues that, in the opinion of the investigator, would impact the ability of the family to complete the study
Interventions	Infants in the extended caffeine treatment arm will, beginning the next day after stopping routine caffeine treatment, receive 5 mg/kg/day of caffeine base and increase to 5 mg/kg/twice a day (BID) of caffeine base beginning at 36 weeks + 0 days PMA and continuing the BID doses through 42 weeks + 6 days PMA Infants in the placebo arm will, beginning the next day after stopping routine caffeine treatment, receive the equivalent (to study drug) volume of placebo daily and increase to the equivalent (to study drug) volume placebo BID through 42 weeks + 6 days PMA
Outcomes	Primary outcomes: Compare the extent of IH exposure, from randomization through 42 weeks + 6 days PMA Compare changes in a panel of inflammation‐related cytokines and chemokines, from enrollment to the target age of 38 weeks + 0 days PMA Compare changes in quantitative MRI structural, microstructural from enrollment to 43 to 46 weeks PMA Secondary outcomes: Association between salivary caffeine concentration and IH outcomes Determine whether caffeine effects on changes in inflammatory or MRI biomarkers from baseline to follow‐up are mediated by caffeine‐related reduced IH
Starting date	18 January 2019
Contact information	Principal Investigator: Carl E Hunt, MD, Children's Research Institute
Comparison
Notes	Enrollment ended 31 July 2023. The study will be unblinded at the end of October at the earliest. Primary results are scheduled to be released in spring 2024.