Efficacy and safety of methylxanthines in very low birthweight infants

Efficacy and safety of methylxanthines in very low birthweight infants: a randomised controlled trial

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN44364365

Enrollment

2006

Registered

2005-09-05

Start date

1999-10-01

Completion date

Unknown

Last updated

2017-05-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Apnea of prematurity Neonatal Diseases Apnea of prematurity

Interventions

Control arm: caffeine will be administered intravenously or orally (via feeding tube) as follows: Loading dose 20 mg/kg caffeine citrate

maintenance dose 5 mg/kg once every 24 hours. The volume of the maintenance dose will be adjusted every 7 days according to the actual body weight on that day. In case of persistent apnea, the respons

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Birth weight 500-1250 g 2. Postnatal age day 1-day 10, either sex 3. Infant considered a candidate for methylxanthine therapy by clinical staff

Exclusion criteria

Exclusion criteria: 1. Dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment 2. Unlikely to comply with long-term follow-up 3. Prior treatment with a methylxanthine

Design outcomes

Primary

Measure	Time frame
Combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months	—

Secondary

Measure	Time frame
1. Neonatal complications typically associated with respiratory insufficiency and very low birth weight (VLBW): 1.1. Bronchopulmonary dysplasia (BPD) is diagnosed in all infants who still require supplemental oxygen at a postconceptual age of 36 weeks. In addition, quantitative comparisons of the duration of support will be performed (days on positive pressure ventilation via endotracheal tube, days on non-invasive continuous positive airway pressure [CPAP], days in oxygen) 1.2. Intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and ventriculomegaly are diagnosed ultrasonographically. Serial cranial ultrasound assessments are routinely performed in VLBW infants to detect hemorrhagic and ischemic changes. The worst scans obtained between days 14 and 28, and between 34-36 weeks post conception, respectively, will be recorded 1.3. Necrotising enterocolitis (NEC) is diagnosed at surgery, at autopsy, or by either the finding of pneumatosis intestinalis, hepatobiliary gas or free intraperitoneal air on abdominal X-ray. In the absence of these findings, suspected NEC is recorded in any infant in whom enteral feeds are withheld for more than 5 days, because of symptoms and signs suggestive of NEC 1.4. Retinopathy of prematurity (ROP) is diagnosed at routine ophthalmologic examinations, beginning at 32 weeks postconceptional age. The severity of ROP will be graded according to the international classification of ROP 2. Weight gain and head circumference will be recorded weekly until discharge from the study centre 3. Functional status at 5 years and at 11-12 years	—

Measure

Time frame

1. Neonatal complications typically associated with respiratory insufficiency and very low birth weight (VLBW): 1.1. Bronchopulmonary dysplasia (BPD) is diagnosed in all infants who still require supplemental oxygen at a postconceptual age of 36 weeks. In addition, quantitative comparisons of the duration of support will be performed (days on positive pressure ventilation via endotracheal tube, days on non-invasive continuous positive airway pressure [CPAP], days in oxygen) 1.2. Intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and ventriculomegaly are diagnosed ultrasonographically. Serial cranial ultrasound assessments are routinely performed in VLBW infants to detect hemorrhagic and ischemic changes. The worst scans obtained between days 14 and 28, and between 34-36 weeks post conception, respectively, will be recorded 1.3. Necrotising enterocolitis (NEC) is diagnosed at surgery, at autopsy, or by either the finding of pneumatosis intestinalis, hepatobiliary gas or free intraperitoneal air on abdominal X-ray. In the absence of these findings, suspected NEC is recorded in any infant in whom enteral feeds are withheld for more than 5 days, because of symptoms and signs suggestive of NEC 1.4. Retinopathy of prematurity (ROP) is diagnosed at routine ophthalmologic examinations, beginning at 32 weeks postconceptional age. The severity of ROP will be graded according to the international classification of ROP 2. Weight gain and head circumference will be recorded weekly until discharge from the study centre 3. Functional status at 5 years and at 11-12 years

—

Countries

Australia, Canada, Germany, Israel, Netherlands, Sweden, Switzerland, United Kingdom, United States of America

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 27, 2026