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Apnea of PrematurityPhase 3NCT00182312

Caffeine for Apnea of Prematurity (CAP)

A Phase 3 study testing Caffeine citrate injection in people with Apnea of Prematurity, run by McMaster University at 34 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages Up to 10 days
Conditions the study is for
Apnea of Prematurity
What is being tested?
Caffeine citrate injection
How many people
2,000 participants
Where
34 sitesin 9 countries
Study dates
Oct 1999to Jul 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 10 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • birthweight 500 to 1250 grams
  • postnatal age day 1 to day 10
  • infant considered a candidate for methylxanthine therapy by clinical staff

Who cannot join

  • 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

Trial locations and contacts

34 sites in 9 countries.

34 sites in 9 countries

Canada15 sites

  • Foothills Hospital

    Calgary, Alberta, T2N 4N1

  • McMaster University

    Hamilton, Ontario, L8S 4J9

  • Kingston General Hospital

    Kingston, Ontario, K7L 2V7

  • Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • Royal Victoria Hospital

    Montreal, Quebec, H3A 1A1

  • Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1L 3L5

  • Royal University Hospital

    Saskatoon, Saskatchewan, S7N 0W8

  • University of Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Sunnybrook & Women's College Health Science Centre

    Toronto, Ontario, M5S 1B2

  • Children's & Women's Health Centre of BC

    Vancouver, British Columbia, V6H 3V4

  • Victoria General Hospital

    Victoria, British Columbia, V8Z 6R5

  • Windsor Regional Hospital

    Windsor, Ontario, N8W 1L9

  • St. Boniface General Hospital

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

Australia4 sites

  • Women's & Children's Hospital

    Adelaide, South Australia, 5006

  • Canberra Hospital

    Canberra, Australian Capital Territory, 2605

  • Mercy Hospital for Women

    Melbourne, Victoria, 3002

  • Royal Women's Hospital

    Melbourne, Victoria, 3053

Other trials in Australia

Israel3 sites

  • Soroka University Medical Center

    Beersheba, 84101

  • Meir General Hospital

    Kfar Saba, 44281

  • Kaplan Medical Center

    Rehovot

Other trials in Israel

Switzerland3 sites

  • University Children's Hospital Basel

    Basel, CH-4005

  • University Hospitals of Geneve

    Geneva, 1211

  • University of Zurich

    Zurich, CH-8091

Other trials in Switzerland

United Kingdom3 sites

  • Royal Maternity Hospital

    Belfast, Northern Ireland, BT12 6BB

  • South Cleveland Hospital

    Middlesbrough, TS4 3BW

  • Royal Victoria Infirmary

    Newcastle upon Tyne, NE1 4LP

Other trials in United Kingdom

Germany2 sites

  • Ludwig Maximilian University

    Munich, 81377

  • University of Tuebingen

    Tübingen, D-72076

Other trials in Germany

Netherlands2 sites

  • Academisch Medisch Centrum

    Amsterdam, 1100 DD

  • University Hospital Maastricht

    Maastricht

Other trials in Netherlands

United States1 site

  • Brooklyn Hospital Center

    Brooklyn, New York, 11201

Other trials in United States

Sweden1 site

  • Astrid Lindgren's Children's Hospital

    Stockholm, SE-17176

Other trials in Sweden

About this study

Official title: 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.

Being tested
Caffeine citrate injection
Keywords
preterm infants, very low birthweight, apnea of prematurity, methylxanthines, developmental disabilities
Medical subject headings
Apnea, Developmental Disabilities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Caffeine citrate injectionDrug

    Also called CafCit

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months.

    Measured: corrected age of 18 months

Secondary outcomes (6)

  1. bronchopulmonary dysplasia

    Measured: discharge home

  2. necrotizing enterocolitis

    Measured: discharge home

  3. brain injury: intra- and periventricular hemorrhage, periventricular leucomalacia and/or ventriculomegaly

    Measured: discharge home

  4. retinopathy of prematurity

    Measured: discharge home

  5. growth failure

    Measured: corrected age of 18 months

  6. functional status at 5 years and at 11-12 years

    Measured: corrected age of 5 years and chronological age of 11-12 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2005 (estimated)
  2. Study startOct 1999
  3. Primary completionMar 2007
  4. Study completionJul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
2,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00182312
Sponsor's protocol ID
CTMG-1999-CAP
Other IDs
ISRCTN44364365, MCT-13288, MOP-102601
Status last verified
Sep 2016
First submitted
13 Sep 2005
Last updated
22 Mar 2018
Results posted
No
Data monitoring committee
Yes

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.

    PubMed 16707748

  • 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.

    PubMed 17989382

  • 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.

    PubMed 19926098

  • 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.

    PubMed 22253394

  • 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.

    PubMed 21173002

  • 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.

    PubMed 24496539

  • 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.

    PubMed 24840756

  • 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.

    PubMed 28707987

  • 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.

    PubMed 28437520

  • 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.

    PubMed 25784749

  • 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.

    PubMed 25641237

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Caffeine citrate injection in people with Apnea of Prematurity, run by McMaster University at 34 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Canada, Australia, Israel, Switzerland, United Kingdom and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months. (time frame: corrected age of 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00182312, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2018.

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