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

Официальное название

Caffeine Therapy in Preterm Infants Born at 28-34 Weeks: A Pilot Placebo-Controlled Randomized Controlled Trial

Обзор

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.

Подробное описание

Despite the widespread use of caffeine for extremely preterm infants, a significant knowledge gap exists regarding its efficacy for infants (28+0 to 34+6 weeks' gestation) who require respiratory support. This patient population is at increased risk for respiratory morbidity and prolonged hospitalization, yet clinical practice regarding caffeine use remains highly variable.

The CARES-Pilot is a single-center, pilot randomized controlled trial (RCT) designed to assess the feasibility of a larger, definitive trial. The long-term goal of the definitive trial is to determine if routine caffeine administration reduces the time to discharge alive from the NICU.

This pilot study utilizes a double-blind, placebo-controlled, parallel-group design. Eligible infants are those born between 28+0 and 34+6 weeks of gestation who require invasive or non-invasive respiratory support within the first 72 hours of life. Participants are randomized to receive either caffeine base (10 mg/kg loading dose, followed by 5 mg/kg daily maintenance) or an equivalent volume of normal saline (placebo).

The primary focus of this pilot phase is to evaluate four key feasibility outcomes using a "traffic light" approach with pre-specified progression criteria:

Recruitment and Eligibility: Assessing the proportion of eligible infants whose parents provide consent and are successfully randomized.

Treatment Fidelity: Monitoring adherence to the blinded treatment protocol by the clinical and pharmacy teams.

Retention: Evaluating the number of participants who complete the study through to the primary clinical endpoint.

Data Completeness: Ensuring the reliability of data collection for secondary clinical outcomes.

Secondary clinical objectives include measuring the time to discharge alive from the NICU (the planned primary outcome for the definitive trial), duration of respiratory support, time to full enteral feeds, and neurodevelopmental status at discharge using the Test of Infant Motor Performance (TIMP). This pilot will also explore the acceptability of the trial protocol among healthcare providers and parents through surveys and focus groups.

The findings from this pilot study will be used to refine the protocol, calculate a precise sample size for the definitive multicenter RCT, and determine the viability of expanding the study to other sites.

Вмешательства

• Препарат Caffeine
  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).
• Другое Placebo
  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

Первичные конечные точки

• Recruitment/Eligibility Proportion [Срок оценки: Through study completion, up to 24 months]
• Treatment Adherence Proportion [Срок оценки: From randomization until 24 hours after weaning from respiratory support]
• Retention Proportion [Срок оценки: Through study completion, up to 24 months]

Вторичные конечные точки (12)

• Time to Discharge Alive from the NICU [Срок оценки: From the date of randomization until the date of discharge alive from NICU, assessed up to 24 months]
• Parent/Guardian Acceptability [Срок оценки: Within 7 days prior to infant's NICU discharge]
• Healthcare Provider Acceptability [Срок оценки: Through recruitment completion, an average of 24 months]
• Data Completeness [Срок оценки: At the end of the recruitment period, approximately 24 months]
• Significant Apnea Frequency [Срок оценки: From randomization until 24 hours after weaning from respiratory support]
• Total Duration of Respiratory Support [Срок оценки: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months]
• Duration of Invasive Support [Срок оценки: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months]
• Time to Full Enteral Feeding [Срок оценки: From the date of first enteral feeding until the date when the targeted feeding volume is achieved, average of 14 days]
• Time to Full Oral Feeding [Срок оценки: From the date of birth until the date of full oral feeding is achieved, an average of 6 weeks]
• Duration of Total Parenteral Nutrition (TPN) [Срок оценки: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age]
• PMA at Weaning [Срок оценки: At the time of weaning from respiratory support, an average of 4 to 6 weeks after birth]
• PMA at Discharge [Срок оценки: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Kingston Health Science Center — Kingston

Публикации

• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07456670 · TRAQ 73767

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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