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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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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