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

December 3, 2014 updated by: McMaster University

Long-Term Effects On Sleep Of Methylxanthine Therapy For Apnea Of Prematurity

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

201

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Melbourne, Australia
        • Mercy Hospital for Women
      • Melbourne, Australia
        • Royal Women's Hospital
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4J9
        • McMaster University Medical Centre
      • Toronto, Ontario, Canada, M5S 1B2
        • Sunnybrook Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 7 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: placebo
Drug: placebo
normal saline
ACTIVE_COMPARATOR: caffeine
Drug: Caffeine citrate injection

Loading dose: 20 mg/kg administered over at least 30 minutes via IV infusion or over at least 10 minutes via slow IV injection.

Daily maintenance dose (to commence at least 24 hours after loading dose): 5 mg/kg, administered over at least 10 minutes via IV infusion, or over at least 5 minutes via slow IV injection. Maintenance dose to be adjusted for body weight every 7 days. If indicated, maintenance dose may be increased to a maximum of 10 mg/kg. May be given orally once full enteral feeds are established.

Duration of treatment: discontinue after infant has tolerated at least 5 consecutive days without positive pressure support AND when the infant is judged by the attending clinician to be no longer a candidate for methylxanthine therapy.

Other Names:
  • CafCit

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Aim 1: The primary outcome is the mean actual sleep time as measured by actigraphy, between subjects who received caffeine vs placebo.
Time Frame: 5-7 years
5-7 years
Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo.
Time Frame: 5-7 years
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.
Time Frame: 5-7 years
5-7 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: Carole Marcus, M.B.B.Ch., University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2009

Primary Completion (ACTUAL)

July 1, 2013

Study Completion (ACTUAL)

July 1, 2013

Study Registration Dates

First Submitted

November 24, 2009

First Submitted That Met QC Criteria

November 24, 2009

First Posted (ESTIMATE)

November 25, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

December 5, 2014

Last Update Submitted That Met QC Criteria

December 3, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIH-R01HL098045
  • R01HL098045 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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