Caffeine for Apnea of Prematurity (CAP)

Apnea of Prematurity Clinical Trial

Official title:

Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00182312
• Other study ID #: CTMG-1999-CAP
• Secondary ID: ISRCTN44364365MC
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: March 20, 2018
• Start date: October 1999
• Est. completion date: July 2016

Study information

• Verified date: September 2016
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2000
• Est. completion date: July 2016
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 10 Days

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Apnea of Prematurity
• Premature Birth

Intervention

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.

Locations

Country	Name	City	State
Australia	Women's & Children's Hospital	Adelaide	South Australia
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Mercy Hospital for Women	Melbourne	Victoria
Australia	Royal Women's Hospital	Melbourne	Victoria
Canada	Foothills Hospital	Calgary	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	University of Sherbrooke	Sherbrooke	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook & Women's College Health Science Centre	Toronto	Ontario
Canada	Children's & Women's Health Centre of BC	Vancouver	British Columbia
Canada	Victoria General Hospital	Victoria	British Columbia
Canada	Windsor Regional Hospital	Windsor	Ontario
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Germany	Ludwig Maximilian University	Munich
Germany	University of Tuebingen	Tuebingen
Israel	Soroka University Medical Center	Beer Sheva
Israel	Meir General Hospital	Kfar-Saba
Israel	Kaplan Medical Center	Rehovot
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	University Hospital Maastricht	Maastricht
Sweden	Astrid Lindgren's Children's Hospital	Stockholm
Switzerland	University Children's Hospital Basel	Basel
Switzerland	University Hospitals of Geneve	Geneva
Switzerland	University of Zurich	Zurich
United Kingdom	Royal Maternity Hospital	Belfast	Northern Ireland
United Kingdom	South Cleveland Hospital	Middlesbrough
United Kingdom	Royal Victoria Infirmary	Newcastle-upon-Tyne
United States	Brooklyn Hospital Center	Brooklyn	New York

Sponsors (3)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

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

References & Publications (7)

Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, Sinha S, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2010 Mar;156(3):382-7. doi: 10.1016/j.jpeds — View Citation

Doyle LW, Schmidt B, Anderson PJ, Davis PG, Moddemann D, Grunau RE, O'Brien K, Sankaran K, Herlenius E, Roberts R; Caffeine for Apnea of Prematurity Trial investigators. Reduction in developmental coordination disorder with neonatal caffeine therapy. J Pe — View Citation

Dukhovny D, Lorch SA, Schmidt B, Doyle LW, Kok JH, Roberts RS, Kamholz KL, Wang N, Mao W, Zupancic JA; Caffeine for Apnea of Prematurity Trial Group. Economic evaluation of caffeine for apnea of prematurity. Pediatrics. 2011 Jan;127(1):e146-55. doi: 10.15 — View Citation

Schmidt B, Anderson PJ, Doyle LW, Dewey D, Grunau RE, Asztalos EV, Davis PG, Tin W, Moddemann D, Solimano A, Ohlsson A, Barrington KJ, Roberts RS; Caffeine for Apnea of Prematurity (CAP) Trial Investigators. Survival without disability to age 5 years afte — View Citation

Schmidt B, Davis PG, Asztalos EV, Solimano A, Roberts RS. Association between severe retinopathy of prematurity and nonvisual disabilities at age 5 years. JAMA. 2014 Feb 5;311(5):523-5. doi: 10.1001/jama.2013.282153. — View Citation

Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. — View Citation

Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007 Nov 8;357(19):1893-902. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months.		corrected age of 18 months
Secondary	bronchopulmonary dysplasia		discharge home
Secondary	necrotizing enterocolitis		discharge home
Secondary	brain injury: intra- and periventricular hemorrhage, periventricular leucomalacia and/or ventriculomegaly		discharge home
Secondary	retinopathy of prematurity		discharge home
Secondary	growth failure		corrected age of 18 months
Secondary	functional status at 5 years and at 11-12 years		corrected age of 5 years and chronological age of 11-12 years