This trial is active, not recruiting.

Condition apnea of prematurity
Treatment caffeine citrate injection
Phase phase 3
Sponsor McMaster University
Collaborator Canadian Institutes of Health Research (CIHR)
Start date October 1999
End date March 2007
Trial size 2000 participants
Trial identifier NCT00182312, CTMG-1999-CAP, ISRCTN44364365, MCT-13288, MOP-102601


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose prevention

Primary Outcomes

combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months.
time frame: corrected age of 18 months

Secondary Outcomes

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

Eligibility Criteria

Male or female participants up to 10 days old.

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

Additional Information

Official title Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by McMaster University.