Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study
Condition: Apnea of Prematurity
MeSH terms: Apnea; Premature Birth
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Caffeine citrate injection; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; normal saline
Other intervention name(s): CafCit
Intervention MeSH terms: Caffeine; Caffeine citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: preterm infants; very low birthweight; apnea of prematurity; methylxanthines; sleep disturbance; obstructive sleep apnea syndrome; polysomnography; sleep disruption