Efficacy and safety of methylxanthines in very low birthweight infants
| ISRCTN | ISRCTN44364365 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44364365 |
| ClinicalTrials.gov number | NCT00182312 |
| Secondary identifying numbers | MCT-13288; MOP-102601 |
- Submission date
- 05/09/2005
- Registration date
- 05/09/2005
- Last edited
- 25/04/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Neonatal Diseases
Plain English summary of protocol
Background and study aims
Apnea of prematurity is a condition where premature babies stop breathing for short periods. Methylxanthine drugs such as caffeine are used to prevent or treat apnea of prematurity but it is not known whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight. The aim of this study is to clarify whether methylxanthines cause more good than harm in very low birth weight infants.
Who can participate?
Babies during the first 10 days of life with a very low birth weight (500 to 1250 g) who require methylxanthine treatment for apnea of prematurity.
What does the study involve?
Participating babies are randomly allocated to receive either caffeine or placebo (a dummy drug), until drug treatment for apnea of prematurity is no longer needed. Survival and disability rates are compared between the two groups 18 months later.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
McMaster University (Canada)
When is the study starting and how long is it expected to run for?
October 1999 to July 2016
Who is funding the study?
1. Canadian Institutes of Health Research (CIHR) (Canada)
2. MRC Canada
3. NHMRC Australia (supplementary funding to Australian centres only)
Who is the main contact?
Dr Barbara Schmidt
schmidt@mcmaster.ca
Contact information
Scientific
McMaster University
DBCVSRI Level 4 C4-109
Neonatal Trials Group
Hamilton General Hospital Campus
237 Barton Street East
Hamilton
L8L 2X2
Canada
| Phone | +1 (0)905 521 2100 X 40748 |
|---|---|
| schmidt@mcmaster.ca |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Efficacy and safety of methylxanthines in very low birthweight infants: a randomised controlled trial |
| Study acronym | CAP |
| Study objectives | Avoidance of methylxanthines (caffeine) to prevent or treat apnea of prematurity reduces the risk of adverse outcomes in very low birth weight infants. |
| Ethics approval(s) | McMaster University Research Ethics Board approved on 21/05/1999 Amendment for MOP-102601 approved on 15/07/2010 |
| Health condition(s) or problem(s) studied | Apnea of prematurity |
| Intervention | Control arm: caffeine will be administered intravenously or orally (via feeding tube) as follows: Loading dose 20 mg/kg caffeine citrate; maintenance dose 5 mg/kg once every 24 hours. The volume of the maintenance dose will be adjusted every 7 days according to the actual body weight on that day. In case of persistent apnea, the responsible physician will have the option to increase the maintenance dose in two steps to a maximum of 10 mg/kg of caffeine citrate. Intervention group: an equivalent volume of sterile sodium chloride 0.9% without preservative. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Methylxanthines (caffeine) |
| Primary outcome measure | Combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months |
| Secondary outcome measures | 1. Neonatal complications typically associated with respiratory insufficiency and very low birth weight (VLBW): 1.1. Bronchopulmonary dysplasia (BPD) is diagnosed in all infants who still require supplemental oxygen at a postconceptual age of 36 weeks. In addition, quantitative comparisons of the duration of support will be performed (days on positive pressure ventilation via endotracheal tube, days on non-invasive continuous positive airway pressure [CPAP], days in oxygen) 1.2. Intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and ventriculomegaly are diagnosed ultrasonographically. Serial cranial ultrasound assessments are routinely performed in VLBW infants to detect hemorrhagic and ischemic changes. The worst scans obtained between days 14 and 28, and between 34-36 weeks post conception, respectively, will be recorded 1.3. Necrotising enterocolitis (NEC) is diagnosed at surgery, at autopsy, or by either the finding of pneumatosis intestinalis, hepatobiliary gas or free intraperitoneal air on abdominal X-ray. In the absence of these findings, suspected NEC is recorded in any infant in whom enteral feeds are withheld for more than 5 days, because of symptoms and signs suggestive of NEC 1.4. Retinopathy of prematurity (ROP) is diagnosed at routine ophthalmologic examinations, beginning at 32 weeks postconceptional age. The severity of ROP will be graded according to the international classification of ROP 2. Weight gain and head circumference will be recorded weekly until discharge from the study centre 3. Functional status at 5 years and at 11-12 years |
| Overall study start date | 01/10/1999 |
| Completion date | 31/07/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 2006 |
| Key inclusion criteria | 1. Birth weight 500-1250 g 2. Postnatal age day 1-day 10, either sex 3. Infant considered a candidate for methylxanthine therapy by clinical staff |
| Key exclusion criteria | 1. Dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment 2. Unlikely to comply with long-term follow-up 3. Prior treatment with a methylxanthine |
| Date of first enrolment | 01/10/1999 |
| Date of final enrolment | 01/10/2004 |
Locations
Countries of recruitment
- Australia
- Canada
- Germany
- Israel
- Netherlands
- Sweden
- Switzerland
- United Kingdom
- United States of America
Study participating centre
L8L 2X2
Canada
Sponsor information
University/education
Office of the Associate Dean
Research
1200 Main Street West
Room HSC-3N8
Hamilton
L8N 3Z5
Canada
| Phone | +1 (0)905 525 9140 ext. 22465 |
|---|---|
| hsresadm@mcmaster.ca | |
"ROR" |
https://ror.org/02fa3aq29 |
Funders
Funder type
Research organisation
Government organisation / National government
- Alternative name(s)
- Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
- Location
- Canada
Government organisation / National government
- Alternative name(s)
- Medical Research Council, Canada, Medical Research Council, Medical Research Council of Canada, MRC
- Location
- Canada
Government organisation / National government
- Alternative name(s)
- NHMRC
- Location
- Australia
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 18/05/2006 | Yes | No | |
| Results article | results | 08/11/2007 | Yes | No | |
| Results article | results | 01/03/2010 | Yes | No | |
| Results article | results | 01/06/2017 | Yes | No |
Editorial Notes
25/04/2017: Publication reference added.
18/03/2016: Plain English summary added.
15/09/2010: This record was updated to include details of amendment MOP-102601. This trial has completed the recruitment and 18-month follow-up phases and is now in extended follow-up (5 years and 11-12 years). The overall trial end date was extended from 31/03/2009 to 31/07/2016 to accommodate the extended follow up.
