Caffeine for Apnea of Prematurity (CAP)

Study Overview
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Brief Summary
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At least 5 of every 1000 live-born babies are very premature and weigh only 500 to 1250 grams at birth. Approximately 30-40% of these high-risk infants either die or survive with lasting disabilities. The aim of this research is to reduce this heavy burden of illness. A multi-center randomized controlled trial has been designed in which 2000 very low birth weight infants will be enrolled. Our goal is to determine whether the avoidance of methylxanthine drugs will improve survival without disability to 18 months, corrected for prematurity. Methylxanthine drugs such as caffeine are used to prevent or treat periodic breathing and breath-holding spells in premature infants. However, there is a striking lack of evidence for the long-term efficacy and safety of this therapy. Methylxanthines block a naturally occurring substance, called adenosine, which protects the brain during episodes of oxygen deficiency. Such episodes are common in infants who are treated with methylxanthines. It is possible that methylxanthines may worsen the damage caused by lack of oxygen. Therefore, this trial will clarify whether methylxanthines cause more good than harm in very low birth weight infants.

Official Title
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Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants

Conditions
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Apnea of Prematurity

Intervention / Treatment
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* Drug: Caffeine citrate injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: birthweight 500 to 1250 grams postnatal age day 1 to day 10 infant considered a candidate for methylxanthine therapy by clinical staff Exclusion Criteria: dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment unlikely to comply with long-term follow-up prior treatment with a methylxanthine

Ages Eligible for Study
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Maximum Age: 10 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months. |  | corrected age of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bronchopulmonary dysplasia |  | discharge home | 
| necrotizing enterocolitis |  | discharge home | 
| brain injury: intra- and periventricular hemorrhage, periventricular leucomalacia and/or ventriculomegaly |  | discharge home | 
| retinopathy of prematurity |  | discharge home | 
| growth failure |  | corrected age of 18 months | 
| functional status at 5 years and at 11-12 years |  | corrected age of 5 years and chronological age of 11-12 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm infants, very low birthweight, apnea of prematurity, methylxanthines, developmental disabilities