Caffeine Therapy in Preterm Infants Born at 28-34 Weeks: A Pilot Placebo-Controlled Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Recruitment/Eligibility Proportion
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 0 Days 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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).
研究组 & 干预措施
Caffeine Citrate Group
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
干预措施: Caffeine (Drug)
Placebo Group
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.
干预措施: Placebo (Other)
结局指标
主要结局
Recruitment/Eligibility Proportion
时间窗: Through study completion, up to 24 months
Ratio of enrolled/randomized infants to total eligible infants screened.
Treatment Adherence Proportion
时间窗: From randomization until 24 hours after weaning from respiratory support
Percentage of per-protocol doses (caffeine/placebo) successfully administered
Retention Proportion
时间窗: Through study completion, up to 24 months
Percentage of randomized infants who complete the study protocol until NICU discharge
次要结局
- 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)
- Total Duration of Respiratory Support(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(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(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(From the date of birth until the date of full oral feeding is achieved, an average of 6 weeks)
- PMA at Weaning(At the time of weaning from respiratory support, an average of 4 to 6 weeks after birth)
- PMA at Discharge(At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age)
- Rate of New Invasive Ventilation(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)
- In-hospital Mortality(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)
- Test of Infant Motor Performance (TIMP) Score(At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age)
- Duration of Total Parenteral Nutrition (TPN)(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)
- Bronchopulmonary dysplasia (BPD)(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)
- Pulmonary Hemorrhage(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)
- Pneumothorax(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)
- Necrotizing Enterocolitis (NEC) Bell's Stage 2 or more(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)
- Gastrointestinal Surgery(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)
- Intraventricular hemorrhage (IVH)(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)
- Periventricular Leukomalacia (PVL)(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)
- Seizure(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)
- Patent ductus arteriosus (PDA) Treatment(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)
- Retinopathy of Prematurity (ROP) Stage(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)
- Late Onset Sepsis(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)
研究者
Eyad Bitar
Assistant Professor, Department of Pediatrics
Queen's University