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

This study has been completed.
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
McMaster University
ClinicalTrials.gov Identifier:
NCT01020357
First received: November 24, 2009
Last updated: November 4, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Apnea of Prematurity
Drug: Caffeine citrate injection
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Long-Term Effects On Sleep Of Methylxanthine Therapy For Apnea Of Prematurity

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo. [ Time Frame: 5-7 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Questionnaire data: National Sleep Foundation (NSF) and Pediatric Sleep Questionnaire (PSQ) scores [ Time Frame: 5-7 years ] [ Designated as safety issue: No ]
  • Polysomnography data: Sleep architecture, arousal index, central apnea index, SpO2 and periodic limb movement index. [ Time Frame: 5-7 years ] [ Designated as safety issue: No ]

Enrollment: 201
Study Start Date: November 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: CafCit
Placebo Comparator: placebo Drug: placebo
normal saline

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.

  Eligibility

Ages Eligible for Study:   5 Years to 7 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01020357

Locations
Australia
Mercy Hospital for Women
Melbourne, Australia
Royal Women's Hospital
Melbourne, Australia
Canada, Ontario
McMaster University Medical Centre
Hamilton, Ontario, Canada, L8S 4J9
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M5S 1B2
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Carole Marcus, M.B.B.Ch. University of Pennsylvania
  More Information

Publications:
Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT01020357     History of Changes
Other Study ID Numbers: NIH-R01HL098045, R01HL098045
Study First Received: November 24, 2009
Last Updated: November 4, 2013
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
preterm infants
very low birthweight
apnea of prematurity
methylxanthines
sleep disturbance
obstructive sleep apnea syndrome
polysomnography
sleep disruption

Additional relevant MeSH terms:
Apnea
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory
Caffeine
Caffeine citrate
Central Nervous System Agents
Central Nervous System Stimulants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014