- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00182312
Caffeine for Apnea of Prematurity (CAP)
Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Australian Capital Territory
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Canberra, Australian Capital Territory, Australia, 2605
- Canberra Hospital
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South Australia
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Adelaide, South Australia, Australia, 5006
- Women's & Children's Hospital
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Victoria
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Melbourne, Victoria, Australia, 3002
- Mercy Hospital for Women
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Melbourne, Victoria, Australia, 3053
- Royal Women's Hospital
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Quebec, Canada, G1L 3L5
- Centre Hospitalier Universitaire de Quebec
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Alberta
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Calgary, Alberta, Canada, T2N 4N1
- Foothills Hospital
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3V4
- Children's & Women's Health Centre of BC
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Victoria, British Columbia, Canada, V8Z 6R5
- Victoria General Hospital
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Manitoba
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Winnipeg, Manitoba, Canada, R2H 2A6
- St. Boniface General Hospital
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New Brunswick
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Moncton, New Brunswick, Canada, E1C 6Z8
- Moncton Hospital
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Ontario
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Hamilton, Ontario, Canada, L8S 4J9
- McMaster University
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Kingston, Ontario, Canada, K7L 2V7
- Kingston General Hospital
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Ottawa, Ontario, Canada, K1H 8L6
- Ottawa Hospital
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Toronto, Ontario, Canada, M5G 1X5
- Mount Sinai Hospital
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Toronto, Ontario, Canada, M5S 1B2
- Sunnybrook & Women's College Health Science Centre
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Windsor, Ontario, Canada, N8W 1L9
- Windsor Regional Hospital
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Quebec
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Montreal, Quebec, Canada, H3A 1A1
- Royal Victoria Hospital
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Sherbrooke, Quebec, Canada, J1H 5N4
- University of Sherbrooke
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Saskatchewan
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Saskatoon, Saskatchewan, Canada, S7N 0W8
- Royal University Hospital
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Munich, Germany, 81377
- Ludwig Maximilian University
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Tuebingen, Germany, D-72076
- University of Tuebingen
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Beer Sheva, Israel, 84101
- Soroka University Medical Center
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Kfar-Saba, Israel, 44281
- Meir General Hospital
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Rehovot, Israel
- Kaplan Medical Center
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Amsterdam, Netherlands, 1100 DD
- Academisch Medisch Centrum
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Maastricht, Netherlands
- University Hospital Maastricht
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Stockholm, Sweden, SE-17176
- Astrid Lindgren's Children's Hospital
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Basel, Switzerland, CH-4005
- University Children's Hospital Basel
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Geneva, Switzerland, 1211
- University Hospitals of Geneve
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Zurich, Switzerland, CH-8091
- University of Zurich
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Middlesbrough, United Kingdom, TS4 3BW
- South Cleveland Hospital
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Newcastle-upon-Tyne, United Kingdom, NE1 4LP
- Royal Victoria Infirmary
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Northern Ireland
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Belfast, Northern Ireland, United Kingdom, BT12 6BB
- Royal Maternity Hospital
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New York
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Brooklyn, New York, United States, 11201
- Brooklyn Hospital Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months.
Time Frame: corrected age of 18 months
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corrected age of 18 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
bronchopulmonary dysplasia
Time Frame: discharge home
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discharge home
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necrotizing enterocolitis
Time Frame: discharge home
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discharge home
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brain injury: intra- and periventricular hemorrhage, periventricular leucomalacia and/or ventriculomegaly
Time Frame: discharge home
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discharge home
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retinopathy of prematurity
Time Frame: discharge home
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discharge home
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growth failure
Time Frame: corrected age of 18 months
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corrected age of 18 months
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functional status at 5 years and at 11-12 years
Time Frame: corrected age of 5 years and chronological age of 11-12 years
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corrected age of 5 years and chronological age of 11-12 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Barbara K Schmidt, MD, 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
Publications and helpful links
General 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. doi: 10.1056/NEJMoa054065.
- 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. doi: 10.1056/NEJMoa073679.
- 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. No abstract available.
- 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.
- Doyle LW, Ranganathan S, Cheong JLY. Neonatal Caffeine Treatment and Respiratory Function at 11 Years in Children under 1,251 g at Birth. Am J Respir Crit Care Med. 2017 Nov 15;196(10):1318-1324. doi: 10.1164/rccm.201704-0767OC.
- Schmidt B, Roberts RS, Anderson PJ, Asztalos EV, Costantini L, Davis PG, Dewey D, D'Ilario J, Doyle LW, Grunau RE, Moddemann D, Nelson H, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity (CAP) Trial Group. Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of Prematurity: An 11-Year Follow-up of the CAP Randomized Clinical Trial. JAMA Pediatr. 2017 Jun 1;171(6):564-572. doi: 10.1001/jamapediatrics.2017.0238.
- 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, Bohm 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Respiration Disorders
- Signs and Symptoms, Respiratory
- Pregnancy Complications
- Obstetric Labor Complications
- Obstetric Labor, Premature
- Apnea
- Premature Birth
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Purinergic Antagonists
- Purinergic Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Caffeine
- Caffeine citrate
Other Study ID Numbers
- CTMG-1999-CAP
- ISRCTN44364365 (REGISTRY: Current Controlled Trials)
- MCT-13288 (OTHER_GRANT: CIHR)
- MOP-102601 (OTHER_GRANT: CIHR)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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