Intermittent Hypoxia and Caffeine in Infants Born Preterm

• Status: Recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's National Research Institute; Children's Research Institute
• Collaborators: American SIDS Institute; Beth Israel Medical Center; Boston University; Children's Hospital of Philadelphia; Dartmouth-Hitchcock Medical Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Johns Hopkins All Children's Hospital; University of Massachusetts, Worcester; Walter Reed National Military Medical Center; Washington Hospital Center
• Treatments: Caffeine; Caffeine citrate; Citric Acid

Criteria

Inclusion Criteria:

1. Male and female infants born preterm at ≤30 weeks + 6 days post menstrual age

2. Current treatment with routine caffeine

3. PMA 32 weeks + 0 days - 36 weeks + 6 days

4. Anticipated last dose of routine caffeine will be by 36 weeks + 5 days

5. At least 12 hours of breathing room air with no ventilatory support other than on room air nasal air flow therapy regardless of flow rate, or on room air and receiving nasal CPAP, and relapse not anticipated.

6. Able to tolerate enteral medications

7. It is feasible to administer the first dose of study drug no later than 36 weeks + 6 days PMA

Exclusion Criteria:

1. Intraventricular hemorrhage Grade III-IV or cystic periventricular leukomalacia

2. Current or prior treatment for seizures

3. Current or prior treatment for cardiac arrhythmias

4. Known renal or hepatic dysfunction that in the opinion of the investigator would have a clinically relevant impact on caffeine metabolism

5. Major malformation, inborn error of metabolism, chromosomal abnormality

6. Presence of a condition for which survival to discharge unlikely

7. 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