Caffeine for Infants Born at 28 to 34 Weeks Receiving Respiratory Support

NCT07456670 | Not Yet Recruiting Phase 2

• 1 other identifier: TRAQ 73767
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot clinical trial is to test if it is possible to conduct a larger study on the use of caffeine in preterm infants who need help with their breathing. It will also look at whether caffeine helps these infants get healthy enough to leave the hospital sooner. The main questions the researchers aim to answer are: Can the investigators successfully recruit and keep enough participants in the study? Do the medical teams follow the study drug instructions correctly? Does caffeine reduce the total time infants spend in the Neonatal Intensive Care Unit (NICU)? Researchers will compare caffeine to a placebo (a look-alike substance with no active medicine) to see if caffeine is a helpful treatment for babies born between 28 and 34 weeks of gestation who are using a breathing machine or oxygen. Participants will: Be randomly assigned to receive either caffeine or a placebo through an IV or a feeding tube. Receive the study treatment once a day as long as they require respiratory support (and for 24 hours after they stop). Be monitored by the research team for clinical outcomes like feeding progress, breathing stability, and growth until they are discharged from the hospital.

Conditions

Preterm Birth; Caffeine; Neonatal Outcomes

Keywords

Caffeine; Neonatal Intensive Care Unit; Prematurity; RCT; NICU; Pilot Study

Outcome Measures

Primary Outcomes (3)

• Recruitment/Eligibility Proportion

  Ratio of enrolled/randomized infants to total eligible infants screened.

  Through study completion, up to 24 months

• Treatment Adherence Proportion

  Percentage of per-protocol doses (caffeine/placebo) successfully administered

  From randomization until 24 hours after weaning from respiratory support

• Retention Proportion

  Percentage of randomized infants who complete the study protocol until NICU discharge

  Through study completion, up to 24 months

Secondary Outcomes (26)

• Time to Discharge Alive from the NICU

  From the date of randomization until the date of discharge alive from NICU, assessed up to 24 months

• Parent/Guardian Acceptability

  Within 7 days prior to infant's NICU discharge

• Healthcare Provider Acceptability

  Through recruitment completion, an average of 24 months

• Data Completeness

  At the end of the recruitment period, approximately 24 months

• Significant Apnea Frequency

  From randomization until 24 hours after weaning from respiratory support

Study Arms (2)

Caffeine Citrate Group

EXPERIMENTAL

Infants in this arm will receive a loading dose of caffeine base (10 mg/kg), followed by a daily maintenance dose (5 mg/kg). The study drug will be administered intravenously or enterally (once full oral feeds are established) until 24 hours after the successful weaning of respiratory support

Drug: Caffeine

Placebo Group

PLACEBO COMPARATOR

Infants in this arm will receive an equivalent volume of 0.9% normal saline (placebo) instead of caffeine. The loading dose and daily maintenance doses will follow the same schedule and administration routes (intravenous or enteral) as the experimental arm. The placebo will be administered until 24 hours after the successful weaning of respiratory support.

Other: Placebo

Interventions

Caffeine DRUG

Infants randomized to this arm will receive caffeine citrate administered as a 10 mg/kg loading dose (caffeine base equivalent), followed by a 5 mg/kg daily maintenance dose (caffeine base equivalent).

Also known as: caffeine Base

Caffeine Citrate Group

Placebo OTHER

Infants randomized to this arm will receive 0.9% normal saline administered in a volume equivalent to the caffeine citrate arm. The placebo will be administered as a loading dose followed by a daily maintenance dose matching the volume and timing of the experimental protocol

Placebo Group

Eligibility Criteria

• Age: 0 Days - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infant born at a gestational age between 28+0 and 34+6 weeks.
• Admitted to the Neonatal Intensive Care Unit (NICU) within the first 72 hours of life.
• Requiring either invasive respiratory support (mechanical ventilation) or non-invasive respiratory support (e.g., CPAP, High Flow Nasal Cannula) within the first 72 hours of life.
• Informed consent obtained from parent(s) or legal guardian(s).

You may not qualify if:

• Presence of dysmorphic features or major congenital malformations that adversely affect life expectancy.
• Known or strongly suspected cyanotic heart disease.
• Infants born at \<28 weeks' gestational age (due to high risk of apnea requiring routine caffeine).
• Late preterm infants born at ≥35+0 weeks' gestational age (due to short NICU stay not allowing for a safe caffeine-free period before discharge).

Sponsors & Collaborators

• Queen's University: lead

Study Sites (1)

Kingston Health Science Center

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (6)

• Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. J Perinatol. 2024 Jun;44(6):785-801. doi: 10.1038/s41372-024-01939-x. Epub 2024 Mar 29.

  PMID: 38553606 BACKGROUND

• Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.

  PMID: 16707748 BACKGROUND

• Iranpour R, Armanian AM, Miladi N, Feizi A. Effect of Prophylactic Caffeine on Noninvasive Respiratory Support in Preterm Neonates Weighing 1250-2000 g: A Randomized Controlled Trial. Arch Iran Med. 2022 Feb 1;25(2):98-104. doi: 10.34172/aim.2022.16.

  PMID: 35429946 BACKGROUND

• Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8.

  PMID: 28126032 BACKGROUND

• Lewis M, Bromley K, Sutton CJ, McCray G, Myers HL, Lancaster GA. Determining sample size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back! Pilot Feasibility Stud. 2021 Feb 3;7(1):40. doi: 10.1186/s40814-021-00770-x.

  PMID: 33536076 BACKGROUND

• Muehlbacher T, Gaertner VD, Bassler D. History of caffeine use in neonatal medicine and the role of the CAP trial. Semin Fetal Neonatal Med. 2020 Dec;25(6):101159. doi: 10.1016/j.siny.2020.101159. Epub 2020 Oct 21. No abstract available.

  PMID: 33129702 BACKGROUND

MeSH Terms

Conditions

Premature Birth

Interventions

Caffeine

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Eyad Bitar, MD

CONTACT

+1 (613) 548-6053; eyad.bitar@queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Pediatrics

Model Details: A randomized, double-blind, 1:1 parallel-group allocation comparing a daily caffeine base to a matched saline placebo

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 6, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-02

Locations

CA (1)