Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study

Phase 3

Completed

• Conditions: Apnea of Prematurity
• Interventions: Drug: placebo; Drug: Caffeine citrate injection

• Registration Number: NCT01020357
• Lead Sponsor: McMaster University

Brief Summary

Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain.

The Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study is a sub-study of the main Caffeine for Apnea of Prematurity (CAP) trial, an international placebo-controlled randomized trial of methylxanthine therapy for apnea of prematurity. This sub-study is designed to take advantage of this cohort of ex-premature, 5-7 year old children who were randomized at birth to receive either caffeine or placebo, and are currently receiving detailed neurocognitive and behavioral assessments in the CAP trial.

Detailed Description

The use of methylxanthines as therapy for apnea of prematurity may be a double-edged sword. Although widely-used, and efficacious for treatment of apnea of prematurity, long-term drug effects have not been rigorously studied. Neonatal methylxanthine therapy may have long-term impacts on sleep organization and ventilatory control. The CAP trial, funded by the Canadian Institutes of Health Research, was initiated due to the paucity of well-controlled data on the long-term effects of methylxanthines in preterm infants. The initial CAP trial was a multicenter, randomized, placebo-controlled trial of caffeine vs placebo as treatment for apnea of prematurity with follow-up to a corrected age of 18 months. 2,006 infants were enrolled. The CAP trial found that methylxanthines reduced the rates of bronchopulmonary dysplasia (BPD) and cerebral palsy (CP), and did not affect mortality. However, concerns remain regarding long-term sequelae of methylxanthine use. The Canadian Institutes of Health Research have therefore funded further follow-up of the entire CAP trial cohort to age 5 years, corrected for prematurity. The key objectives of this study are to examine the impact of methylxanthines on neurocognition and behavior. This ongoing parent study provides an opportunity to determine potential long-term effects of methylxanthines on sleep disorders, and to correlate these findings with daytime functioning. Our overall hypothesis is that methylxanthine use in preterm infants, while beneficial in the short term, results in longstanding abnormalities in the regulation of sleep, and breathing during sleep.

Study Timeline

• Study Start: 2009-11
• Study First Submitted: 2009-11-24
• Study First Submitted QC: 2009-11-24
• Study First Posted: 2009-11-25
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-03
• Last Update Posted: 2014-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 201

Inclusion Criteria

• Males or females aged 5-7 years who are enrolled in the CAP trial.
• Parental/guardian permission (informed consent) and if appropriate, child assent.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	-
caffeine	Caffeine citrate injection	-

Primary Outcome Measures

Name	Time	Method
Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo.	5-7 years
Aim 1: The primary outcome is the mean actual sleep time as measured by actigraphy, between subjects who received caffeine vs placebo.	5-7 years
Aim 3: The primary outcome is the correlation between full-scale IQ from the Wechsler Preschool and Primary Scale of Intelligence (measured in the CAP trial rather than directly from this protocol), sleep time and AHI.	5-7 years

Secondary Outcome Measures

Name	Time	Method
Questionnaire data: National Sleep Foundation (NSF) and Pediatric Sleep Questionnaire (PSQ) scores	5-7 years
Polysomnography data: Sleep architecture, arousal index, central apnea index, SpO2 and periodic limb movement index.	5-7 years

Trial Locations

Locations (4)

McMaster University Medical Centre; 🇨🇦 Hamilton, Ontario, Canada

Mercy Hospital for Women; 🇦🇺 Melbourne, Australia

Royal Women's Hospital; 🇦🇺 Melbourne, Australia

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada