Caffeine for Apnea of Prematurity (CAP) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Apnea of Prematurity	Drug: Caffeine citrate injection	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator) Primary Purpose: Prevention
Official Title:	Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants

Resource links provided by NLM:

MedlinePlus related topics: Birth Weight Caffeine

U.S. FDA Resources

Further study details as provided by Barbara Schmidt, McMaster University:

Primary Outcome Measures:

combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months. [ Time Frame: corrected age of 18 months ]

Secondary Outcome Measures:

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 ]


Estimated Enrollment:	2000
Study Start Date:	October 1999
Study Completion Date:	July 2016
Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Other Name: CafCit

Eligibility


Ages Eligible for Study:	up to 10 Days (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182312

Show 34 Study Locations

Sponsors and Collaborators

McMaster University

Canadian Institutes of Health Research (CIHR)

National Health and Medical Research Council, Australia

Investigators


Study Chair:	Barbara K Schmidt, MD	McMaster University
Study Director:	Robin S Roberts, MTech	McMaster University
Study Director:	Peter Davis, MD	Royal Women's Hospital, Melbourne, Australia
Study Director:	Lex Doyle, MD	Royal Women's Hospital, Melbourne, Australia
Study Director:	Arne Ohlsson, MD	Mount Sinai Hospital, Canada
Study Director:	Alfonso Solimano, MD	Children & Women's Health Centre of BC, Vancouver, Canada
Study Director:	Win Tin, MD	James Cook University Hospital, Middlesbrough, UK
Study Director:	Keith J Barrington, MD	Royal Victoria Hospital/McGill University, Montreal, Canada
Study Director:	Elizabeth Asztalos, MD	Sunnybrook Health Sciences Centre, Toronto, Canada
Study Director:	Deborah Dewey, MD	University of Calgary, Alberta, Canada
Study Director:	Ruth Grunau, MD	University of British Columbia, Vancouver, Canada
Study Director:	Diane Moddemann, MD	University of Manitoba, Winnipeg, Canada
Study Director:	Peter Anderson, PhD	University of Melbourne, Australia

More Information

Publications:

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.

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.

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.2009.09.069. Epub 2009 Nov 18.

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 after neonatal caffeine therapy for apnea of prematurity. JAMA. 2012 Jan 18;307(3):275-82. doi: 10.1001/jama.2011.2024.

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: 10.1542/peds.2010-1014. Epub 2010 Dec 20.

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.

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 Pediatr. 2014 Aug;165(2):356-359.e2. doi: 10.1016/j.jpeds.2014.04.016. Epub 2014 May 17.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Synnes A, Anderson PJ, Grunau RE, Dewey D, Moddemann D, Tin W, Davis PG, Doyle LW, Foster G, Khairy M, Nwaesei C, Schmidt B; CAP Trial Investigator group. Predicting severe motor impairment in preterm children at age 5 years. Arch Dis Child. 2015 Aug;100(8):748-53. doi: 10.1136/archdischild-2014-307695. Epub 2015 Mar 17.

Manley BJ, Roberts RS, Doyle LW, Schmidt B, Anderson PJ, Barrington KJ, Böhm B, Golan A, van Wassenaer-Leemhuis AG, Davis PG; Caffeine for Apnea of Prematurity (CAP) Trial Investigators; Caffeine for Apnea of Prematurity CAP Trial Investigators. Social variables predict gains in cognitive scores across the preschool years in children with birth weights 500 to 1250 grams. J Pediatr. 2015 Apr;166(4):870-6.e1-2. doi: 10.1016/j.jpeds.2014.12.016. Epub 2015 Jan 29.


Responsible Party:	Barbara Schmidt, Principal Investigator, McMaster University
ClinicalTrials.gov Identifier:	NCT00182312 History of Changes
Other Study ID Numbers:	CTMG-1999-CAP ISRCTN44364365 ( Registry Identifier: Current Controlled Trials ) MCT-13288 ( Other Grant/Funding Number: CIHR ) MOP-102601 ( Other Grant/Funding Number: CIHR )
Study First Received:	September 13, 2005
Last Updated:	September 26, 2016

Keywords provided by Barbara Schmidt, McMaster University:


preterm infants very low birthweight apnea of prematurity methylxanthines developmental disabilities

Additional relevant MeSH terms:


Apnea Premature Birth Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory Signs and Symptoms Obstetric Labor, Premature Obstetric Labor Complications Pregnancy Complications Caffeine citrate	Caffeine Central Nervous System Stimulants Physiological Effects of Drugs Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents

ClinicalTrials.gov processed this record on June 23, 2017