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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00182312




Registration number
NCT00182312
Ethics application status
Date submitted
13/09/2005
Date registered
16/09/2005
Date last updated
22/03/2018

Titles & IDs
Public title
Caffeine for Apnea of Prematurity (CAP)
Scientific title
Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants
Secondary ID [1] 0 0
ISRCTN44364365
Secondary ID [2] 0 0
CTMG-1999-CAP
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Apnea of Prematurity 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Sleep apnoea
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn
Reproductive Health and Childbirth 0 0 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Caffeine citrate injection

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months.
Timepoint [1] 0 0
corrected age of 18 months
Secondary outcome [1] 0 0
bronchopulmonary dysplasia
Timepoint [1] 0 0
discharge home
Secondary outcome [2] 0 0
necrotizing enterocolitis
Timepoint [2] 0 0
discharge home
Secondary outcome [3] 0 0
brain injury: intra- and periventricular hemorrhage, periventricular leucomalacia and/or ventriculomegaly
Timepoint [3] 0 0
discharge home
Secondary outcome [4] 0 0
retinopathy of prematurity
Timepoint [4] 0 0
discharge home
Secondary outcome [5] 0 0
growth failure
Timepoint [5] 0 0
corrected age of 18 months
Secondary outcome [6] 0 0
functional status at 5 years and at 11-12 years
Timepoint [6] 0 0
corrected age of 5 years and chronological age of 11-12 years

Eligibility
Key inclusion criteria
* birthweight 500 to 1250 grams
* postnatal age day 1 to day 10
* infant considered a candidate for methylxanthine therapy by clinical staff
Minimum age
No limit
Maximum age
10 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/1999
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2016
Sample size
Target
2000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,SA,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Women's & Children's Hospital - Adelaide
Recruitment hospital [3] 0 0
Mercy Hospital for Women - Melbourne
Recruitment hospital [4] 0 0
Royal Women's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
5006 - Adelaide
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
3053 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
Canada
State/province [2] 0 0
Alberta
Country [3] 0 0
Canada
State/province [3] 0 0
British Columbia
Country [4] 0 0
Canada
State/province [4] 0 0
Manitoba
Country [5] 0 0
Canada
State/province [5] 0 0
New Brunswick
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Canada
State/province [8] 0 0
Saskatchewan
Country [9] 0 0
Germany
State/province [9] 0 0
Munich
Country [10] 0 0
Germany
State/province [10] 0 0
Tuebingen
Country [11] 0 0
Israel
State/province [11] 0 0
Beer Sheva
Country [12] 0 0
Israel
State/province [12] 0 0
Kfar-Saba
Country [13] 0 0
Israel
State/province [13] 0 0
Rehovot
Country [14] 0 0
Netherlands
State/province [14] 0 0
Amsterdam
Country [15] 0 0
Netherlands
State/province [15] 0 0
Maastricht
Country [16] 0 0
Sweden
State/province [16] 0 0
Stockholm
Country [17] 0 0
Switzerland
State/province [17] 0 0
Basel
Country [18] 0 0
Switzerland
State/province [18] 0 0
Geneva
Country [19] 0 0
Switzerland
State/province [19] 0 0
Zurich
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Northern Ireland
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Middlesbrough
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Newcastle-upon-Tyne

Funding & Sponsors
Primary sponsor type
Other
Name
McMaster University
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Canadian Institutes of Health Research (CIHR)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
National Health and Medical Research Council, Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT00182312
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Barbara K Schmidt, MD
Address 0 0
McMaster University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00182312