Optimizing Caffeine Therapy for Hypoxia in Preterm Neonates: A Randomized Trial Assessing Efficacy, Acute Kidney and Brain Injury, Safety, and Pharmacokinetics

The study population will consist of 114 preterm neonates born less than 30 weeks gestational age who have an intravenous (IV) line for which IV medications can be administered and who can have brain and kidney Near Infrared Spectroscopy (NIRS) monitoring.

Eligible participants will be enrolled between 12-96 hours of life after preterm birth and admission to the Meriter NICU. Baseline data will be collected and NIRS monitoring will be started when appropriate as determined by the team based on clinical guidelines and standard of care.

Those participants having kidney oxygenation less than 50 percent (and troubleshooting procedures have occurred and while ensuring brain oxygenation is not below 55 percent) after 48 hours and within the first 14 DOL will be randomized in a 1:1 manner to one of two treatment arms (Arm 1 and Arm 2).

• Arm 1: IV caffeine citrate (20 mg/kg) (n = 51)
• Arm 2: Placebo - same volume of 0.9% Sodium Chloride United States Pharmacopeia (USP) (n=51)

Those participants who do not develop kidney hypoxia during the first 14 DOL will be the normal kidney oxygenation control group and receive no intervention (Arm 3).

• Arm 3: Normal Kidney oxygenation (no intervention) (Approximately n = 12)

Participant accrual will occur over 48 months. Participants will complete all study specific activities during the NICU hospitalization over the course of the first 28 DOL and clinical outcomes will be collected through NICU discharge or 6 months of age, whichever occurs first. Each participant will contribute blood specimens for creatinine and caffeine levels as well as approximately 20-40 urine samples for biomarker analysis.