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

Apnea of Prematurity Clinical Trial

— CAP-S  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020357
• Other study ID #: NIH-R01HL098045
• Secondary ID: R01HL098045
• Status: Completed
• Phase: Phase 3
• First received: November 24, 2009
• Last updated: December 3, 2014
• Start date: November 2009
• Est. completion date: July 2013

Study information

• Verified date: December 2014
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 7 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Apnea of Prematurity
• Premature Birth

Intervention

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.
• placebo
normal saline

Locations

Country	Name	City	State
Australia	Mercy Hospital for Women	Melbourne
Australia	Royal Women's Hospital	Melbourne
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (4)

Marcus CL, Meltzer LJ, Roberts RS, Traylor J, Dix J, D'ilario J, Asztalos E, Opie G, Doyle LW, Biggs SN, Nixon GM, Narang I, Bhattacharjee R, Davey M, Horne RS, Cheshire M, Gibbons J, Costantini L, Bradford R, Schmidt B; Caffeine for Apnea of Prematurity– — View Citation

Marcus CL, Traylor J, Biggs SN, Roberts RS, Nixon GM, Narang I, Bhattacharjee R, Davey MJ, Horne RS, Cheshire M, Gibbons KJ, Dix J, Asztalos E, Doyle LW, Opie GF, D'ilario J, Costantini L, Bradford R, Schmidt B. Feasibility of comprehensive, unattended am — View Citation

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. — View Citation

Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007 Nov 8;357(19):1893-902. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo.		5-7 years	No
Primary	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	No
Secondary	Questionnaire data: National Sleep Foundation (NSF) and Pediatric Sleep Questionnaire (PSQ) scores		5-7 years	No
Secondary	Polysomnography data: Sleep architecture, arousal index, central apnea index, SpO2 and periodic limb movement index.		5-7 years	No