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.

Conditions

• Intermittent Hypoxia

Interventions

DRUG

Caffeine

Infants will be started on oral caffeine base at 5 mg/kg/day. At 36 weeks + 0 days PMA drug dose will be increased to 5 mg/kg BID (total daily dose 10 mg/kg). Dose will be weight-adjusted weekly until NICU (neonatal intensive care unit) discharge. After discharge, all new doses will be calculated from the last weight recorded prior to discharge. The research pharmacy will prepare a bulk oral solution with active drug (caffeine base). While in the hospital, a daily 24-hour supply will be prepared and dispensed. For home administration of study drug, the research pharmacy at each clinical site will prepare and dispense a sufficient quantity of caffeine base solution for outpatient treatment up to 42 weeks + 6 days.

DRUG

Placebos

SyrSpend SF Unflavored will be used as the placebo for the control group infants. The volume of the placebo will match the volume of the study drug.

Sponsors & Collaborators

• Boston University

  collaborator OTHER

• Beth Israel Medical Center

  collaborator OTHER

• University of Massachusetts, Worcester

  collaborator OTHER

• American SIDS Institute

  collaborator OTHER

• Walter Reed National Military Medical Center

  collaborator FED

• Dartmouth-Hitchcock Medical Center

  collaborator OTHER

• Children's Hospital of Philadelphia

  collaborator OTHER

• Johns Hopkins All Children's Hospital

  collaborator OTHER

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Children's National Research Institute

  lead OTHER

Principal Investigators

• Carl E. Hunt, M.D. · Children's Reserach Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

32 Weeks

Max Age

36 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-01-18

Primary Completion

2023-06-01

Completion

2023-06-01

FDA Drug

Yes

Countries

• United States

Study Locations