Caffeine Use in the Management of Preterm Infants

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

Study Overview

• Status: Active, not recruiting
• Conditions: Apnea of Prematurity
• Intervention / Treatment: Drug: Caffeine; Other: Sterile Water Placebo

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Caffeine Group; 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.	Drug: Caffeine; Infants randomized to receive caffeine will continue to receive caffeine at the current weight-based dose (which is the standard of care maintenance dose of 10-15 mg/kg/day) given every 24 hours. The weight-based dose calculated using the weight at the time of enrollment will be the weight-based dose used for the duration of the study. 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. The study drug (caffeine) will be administered for a maximum of 4 weeks. The study drug will be discontinued after 4 weeks or when the infant reaches Step 4 of our institution's oral feeding protocol (oral feeding 6 times per day), whichever comes first. The study drug will also be discontinued if the open-label maintenance caffeine is started by the clinical team based on clinical indications.
Placebo Comparator: Placebo Group; 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.	Other: 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. The placebo will be administered for a maximum of 4 weeks. The placebo will be discontinued after 4 weeks or when the infant reaches Step 4 of our institution's oral feeding protocol (oral feeding 6 times per day), whichever comes first. The placebo will also be discontinued if the open-label maintenance caffeine is started by the clinical team based on clinical indications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to full feeds	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.	From first nutritive oral feed until full oral feeds achieved, up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to discharge	Time to discharge measured in days of hospitalization after randomization	Randomization until discharge, up to 6 weeks
Post menstrual age (PMA) at time of discharge	Post menstrual age at discharge	Randomization until discharge, up to 6 weeks
Number of significant cardiopulmonary events	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.	Randomization until discharge, up to 6 weeks
Weight change	Weight change measured by change in grams	Randomization until discharge, up to 6 weeks

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Investigators: Principal Investigator: Cherry Uy, MD, UC Irvine

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Caffeine; Feeding
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Apnea; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Xanthines; Caffeine
• Other Study ID Numbers: 2659

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No