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

NCT ID: NCT01020357

Last Updated: 2014-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2013-07-31

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.

Conditions

Apnea of Prematurity

Keywords

preterm infants; very low birthweight; apnea of prematurity; methylxanthines; sleep disturbance; obstructive sleep apnea syndrome; polysomnography; sleep disruption

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

caffeine

Group Type: ACTIVE_COMPARATOR

Caffeine citrate injection

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

normal saline

Interventions

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.

Intervention Type: DRUG

placebo

normal saline

Intervention Type: DRUG

Other Intervention Names

CafCit

Eligibility Criteria

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carole Marcus, M.B.B.Ch.

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Mercy Hospital for Women

Melbourne, , Australia

Royal Women's Hospital

Melbourne, , Australia

McMaster University Medical Centre

Hamilton, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Countries

Australia; Canada

References

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.

Reference Type: BACKGROUND

PMID: 16707748 (View on PubMed)

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. doi: 10.1056/NEJMoa073679.

Reference Type: BACKGROUND

PMID: 17989382 (View on PubMed)

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-Sleep Study. Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age. Am J Respir Crit Care Med. 2014 Oct 1;190(7):791-9. doi: 10.1164/rccm.201406-1092OC.

Reference Type: RESULT

PMID: 25171195 (View on PubMed)

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 ambulatory polysomnography in school-aged children. J Clin Sleep Med. 2014 Aug 15;10(8):913-8. doi: 10.5664/jcsm.3970.

Reference Type: RESULT

PMID: 25126039 (View on PubMed)

Other Identifiers

R01HL098045

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIH-R01HL098045

Identifier Type: -

Identifier Source: org_study_id