Caffeine Use in the Management of Preterm Infants

Phase 2

Recruiting

• Conditions: Apnea of Prematurity
• Interventions: Other: Sterile Water Placebo; Drug: Caffeine

• Registration Number: NCT06327152
• Lead Sponsor: University of California, Irvine

Brief Summary

This study aims to assess whether extending the duration of caffeine therapy will help preterm infants achieve full oral feeding faster.

Detailed Description

This study is a randomized, double-blinded, placebo-controlled trial. Infants will be randomized to receive either caffeine or placebo for up to maximum of four additional weeks after meeting clinical criteria to discontinue caffeine. Initiation of oral feeding will be based on standard of care as determined by a neonatal occupational therapist and clinical cues. Oral feedings will be advanced by a standardized 5 step oral feeding protocol. The time it takes to achieve full oral feeds between the treatment and control groups will be compared.

Study Timeline

• Study Start: 2024-02-22
• Study First Submitted: 2024-03-13
• Study First Submitted QC: 2024-03-21
• Study First Posted: 2024-03-25
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-13
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Infants born at equal to or less than 32 weeks and 0 days gestational age AND

• Equal to or greater than 34 weeks and 0 days corrected gestation at time of enrollment.
• Off respiratory support for at least 2 days (nasal canula oxygen, high flow nasal canula, continuous positive airway pressure (CPAP), mechanical ventilation).
• On caffeine and meet criteria to discontinue caffeine.
• No significant cardiopulmonary events for at least 5 days (apnea > 20 seconds, apnea with heart rate (HR) < 80 beats per minute (bpm), HR < 80 bpm with desaturation < 85% or color change).

Exclusion Criteria

• Infants with critical congenital heart disease.
• Infants with neuromuscular conditions affecting respiration.
• Infants with overt brain injury (i.e. severe Grade 3-4 intraventricular hemorrhage, cystic periventricular leukomalacia) that may affect oral feeding.
• Infants with major genetic disorders.
• Infants with anatomic anomalies that will hinder oral feeding.
• Infants who have already progressed to Step 3 (of 5) of our institution's oral feeding protocol (oral feeds 4 times per day).
• Infants who develop necrotizing enterocolitis after enrollment.
• Failure to obtain consent or declined by parents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	Sterile Water Placebo	Infants randomized to the placebo group will be given sterile water at an equivalent volume to the volume if caffeine were to be given, using the previous weight-based caffeine dose. The placebo will be given every 24 hours. The dose/volume will be weight adjusted every 7 days, starting on the day of enrollment. The placebo will be given enterally, via nasogastric tube or by mouth.
Caffeine Group	Caffeine	Infants randomized to receive caffeine will continue to receive caffeine at standard of care maintenance dose of 10-15 mg/kg/day given every 24 hours. The dose will be weight adjusted every 7 days, starting on the day of enrollment. Caffeine will be given enterally, via nasogastric tube or by mouth.

Primary Outcome Measures

Name	Time	Method
Time to full feeds	From first nutritive oral feed until full oral feeds achieved, up to 6 weeks	The primary outcome is time (in days) to full oral bottle feeding or breastfeeding or a combination of both. Full oral bottle feeding is defined as 48 hours of consistent intake of at least 150ml/kg/day of formula or breastmilk. If the subject is on combination of bottle and breastfeeding, two consecutive days of positive weight gain will be used in place of 150ml/kg/day as primary outcome measure.

Secondary Outcome Measures

Name	Time	Method
Time to discharge	Randomization until discharge, up to 6 weeks	Time to discharge measured in days of hospitalization after randomization
Post menstrual age (PMA) at time of discharge	Randomization until discharge, up to 6 weeks	Post menstrual age at discharge
Number of significant cardiopulmonary events	Randomization until discharge, up to 6 weeks	Number of significant cardiopulmonary events defined as apnea \> 20 seconds, apnea with heart rate (HR) \< 80 beats per minute (bpm), HR \< 80 bpm with desaturation \< 85% or color change. Significant events are ones that occur while infant is asleep or lying down.
Weight change	Randomization until discharge, up to 6 weeks	Weight change measured by change in grams

Trial Locations

Locations (1)

UC Irvine Medical Center; 🇺🇸 Orange, California, United States