Apnea of PrematurityPhase 3CAP-SNCT01020357
Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study
A Phase 3 study testing Caffeine citrate injection in people with Apnea of Prematurity, run by McMaster University at 4 sites in 2 countries.
Trial summary
Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain. Read more about this study
- Who is it for?
- Ages 5 to 7 years
- Conditions the study is for
- Apnea of Prematurity
- What is being tested?
- Caffeine citrate injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 201 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Nov 2009to Jul 2013
- 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 5 to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Males or females aged 5-7 years who are enrolled in the CAP trial.
- Parental/guardian permission (informed consent) and if appropriate, child assent.
Who cannot join
None listed.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Australia2 sites
Mercy Hospital for Women
Melbourne
Royal Women's Hospital
Melbourne
Canada2 sites
McMaster University Medical Centre
Hamilton, Ontario, L8S 4J9
Sunnybrook Health Sciences Centre
Toronto, Ontario, M5S 1B2
About this study
Official title: Long-Term Effects On Sleep Of Methylxanthine Therapy For Apnea Of Prematurity
Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain.
The Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study is a sub-study of the main Caffeine for Apnea of Prematurity (CAP) trial, an international placebo-controlled randomized trial of methylxanthine therapy for apnea of prematurity. This sub-study is designed to take advantage of this cohort of ex-premature, 5-7 year old children who were randomized at birth to receive either caffeine or placebo, and are currently receiving detailed neurocognitive and behavioral assessments in the CAP trial.
Read the detailed description
The use of methylxanthines as therapy for apnea of prematurity may be a double-edged sword. Although widely-used, and efficacious for treatment of apnea of prematurity, long-term drug effects have not been rigorously studied. Neonatal methylxanthine therapy may have long-term impacts on sleep organization and ventilatory control. The CAP trial, funded by the Canadian Institutes of Health Research, was initiated due to the paucity of well-controlled data on the long-term effects of methylxanthines in preterm infants. The initial CAP trial was a multicenter, randomized, placebo-controlled trial of caffeine vs placebo as treatment for apnea of prematurity with follow-up to a corrected age of 18 months. 2,006 infants were enrolled. The CAP trial found that methylxanthines reduced the rates of bronchopulmonary dysplasia (BPD) and cerebral palsy (CP), and did not affect mortality. However, concerns remain regarding long-term sequelae of methylxanthine use. The Canadian Institutes of Health Research have therefore funded further follow-up of the entire CAP trial cohort to age 5 years, corrected for prematurity. The key objectives of this study are to examine the impact of methylxanthines on neurocognition and behavior. This ongoing parent study provides an opportunity to determine potential long-term effects of methylxanthines on sleep disorders, and to correlate these findings with daytime functioning. Our overall hypothesis is that methylxanthine use in preterm infants, while beneficial in the short term, results in longstanding abnormalities in the regulation of sleep, and breathing during sleep.
- Conditions
- Apnea of Prematurity
- Being tested
- Caffeine citrate injection, placebo
- Keywords
- preterm infants, very low birthweight, apnea of prematurity, methylxanthines, sleep disturbance, obstructive sleep apnea syndrome, polysomnography, sleep disruption
- Medical subject headings
- Apnea, Parasomnias, Sleep Apnea, Obstructive
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.
placeboDrug
normal saline
| Study group | Role | What they receive |
|---|---|---|
| caffeine | Active comparator | Not described Receives: Drug: Caffeine citrate injection |
| placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aim 1: The primary outcome is the mean actual sleep time as measured by actigraphy, between subjects who received caffeine vs placebo.
Measured: 5-7 years
Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo.
Measured: 5-7 years
Aim 3: The primary outcome is the correlation between full-scale IQ from the Wechsler Preschool and Primary Scale of Intelligence (measured in the CAP trial rather than directly from this protocol), sleep time and AHI.
Measured: 5-7 years
Secondary outcomes (2)
Questionnaire data: National Sleep Foundation (NSF) and Pediatric Sleep Questionnaire (PSQ) scores
Measured: 5-7 years
Polysomnography data: Sleep architecture, arousal index, central apnea index, SpO2 and periodic limb movement index.
Measured: 5-7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Apnea of PrematurityStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 201 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Carole Marcus, M.B.B.Ch., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01020357
- Sponsor's protocol ID
- NIH-R01HL098045
- Other IDs
- R01HL098045
- Acronym
- CAP-S
- Status last verified
- Dec 2014
- First submitted
- 24 Nov 2009
- Last updated
- 5 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
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 16707748Schmidt 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 17989382Marcus CL, Meltzer LJ, Roberts RS, Traylor J, Dix J, D'ilario J, Asztalos E, Opie G, Doyle LW, Biggs SN, Nixon GM, Narang I, Bhattacharjee R, Davey M, Horne RS, Cheshire M, Gibbons J, Costantini L, Bradford R, Schmidt B; Caffeine for Apnea of Prematurity-Sleep Study. Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age. Am J Respir Crit Care Med. 2014 Oct 1;190(7):791-9. doi: 10.1164/rccm.201406-1092OC.
PubMed 25171195Marcus CL, Traylor J, Biggs SN, Roberts RS, Nixon GM, Narang I, Bhattacharjee R, Davey MJ, Horne RS, Cheshire M, Gibbons KJ, Dix J, Asztalos E, Doyle LW, Opie GF, D'ilario J, Costantini L, Bradford R, Schmidt B. Feasibility of comprehensive, unattended ambulatory polysomnography in school-aged children. J Clin Sleep Med. 2014 Aug 15;10(8):913-8. doi: 10.5664/jcsm.3970.
PubMed 25126039
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-Term Effects On Sleep Of Methylxanthine Therapy For Apnea Of Prematurity
- ClinicalTrials.gov ID
- NCT01020357
- Acronym / sponsor ID
- CAP-S / NIH-R01HL098045
- Conditions
- Apnea of Prematurity
- Keywords
- preterm infants, very low birthweight, apnea of prematurity, methylxanthines, sleep disturbance, obstructive sleep apnea syndrome, polysomnography, sleep disruption
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 201 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2009
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain.
The Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study is a sub-study of the main Caffeine for Apnea of Prematurity (CAP) trial, an international placebo-controlled randomized trial of methylxanthine therapy for apnea of prematurity. This sub-study is designed to take advantage of this cohort of ex-premature, 5-7 year old children who were randomized at birth to receive either caffeine or placebo, and are currently receiving detailed neurocognitive and behavioral assessments in the CAP trial.
Detailed description
The use of methylxanthines as therapy for apnea of prematurity may be a double-edged sword. Although widely-used, and efficacious for treatment of apnea of prematurity, long-term drug effects have not been rigorously studied. Neonatal methylxanthine therapy may have long-term impacts on sleep organization and ventilatory control. The CAP trial, funded by the Canadian Institutes of Health Research, was initiated due to the paucity of well-controlled data on the long-term effects of methylxanthines in preterm infants. The initial CAP trial was a multicenter, randomized, placebo-controlled trial of caffeine vs placebo as treatment for apnea of prematurity with follow-up to a corrected age of 18 months. 2,006 infants were enrolled. The CAP trial found that methylxanthines reduced the rates of bronchopulmonary dysplasia (BPD) and cerebral palsy (CP), and did not affect mortality. However, concerns remain regarding long-term sequelae of methylxanthine use. The Canadian Institutes of Health Research have therefore funded further follow-up of the entire CAP trial cohort to age 5 years, corrected for prematurity. The key objectives of this study are to examine the impact of methylxanthines on neurocognition and behavior. This ongoing parent study provides an opportunity to determine potential long-term effects of methylxanthines on sleep disorders, and to correlate these findings with daytime functioning. Our overall hypothesis is that methylxanthine use in preterm infants, while beneficial in the short term, results in longstanding abnormalities in the regulation of sleep, and breathing during sleep.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| caffeine | Active comparator | Drug: Caffeine citrate injection |
| placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 5 to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Males or females aged 5-7 years who are enrolled in the CAP trial.
- Parental/guardian permission (informed consent) and if appropriate, child assent.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine citrate injectionAlso: CafCitLoading 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. | Drug | caffeine |
| placebonormal saline | Drug | placebo |
Primary outcome
Aim 1: The primary outcome is the mean actual sleep time as measured by actigraphy, between subjects who received caffeine vs placebo.
Time frame: 5-7 years
Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo.
Time frame: 5-7 years
Aim 3: The primary outcome is the correlation between full-scale IQ from the Wechsler Preschool and Primary Scale of Intelligence (measured in the CAP trial rather than directly from this protocol), sleep time and AHI.
Time frame: 5-7 years
2 secondary outcomes
Questionnaire data: National Sleep Foundation (NSF) and Pediatric Sleep Questionnaire (PSQ) scores
Time frame: 5-7 years
Polysomnography data: Sleep architecture, arousal index, central apnea index, SpO2 and periodic limb movement index.
Time frame: 5-7 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
- Background: PubMed 16707748Schmidt 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.
- Background: PubMed 17989382Schmidt 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.
- Results publication: PubMed 25171195Marcus CL, Meltzer LJ, Roberts RS, Traylor J, Dix J, D'ilario J, Asztalos E, Opie G, Doyle LW, Biggs SN, Nixon GM, Narang I, Bhattacharjee R, Davey M, Horne RS, Cheshire M, Gibbons J, Costantini L, Bradford R, Schmidt B; Caffeine for Apnea of Prematurity-Sleep Study. Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age. Am J Respir Crit Care Med. 2014 Oct 1;190(7):791-9. doi: 10.1164/rccm.201406-1092OC.
- Results publication: PubMed 25126039Marcus CL, Traylor J, Biggs SN, Roberts RS, Nixon GM, Narang I, Bhattacharjee R, Davey MJ, Horne RS, Cheshire M, Gibbons KJ, Dix J, Asztalos E, Doyle LW, Opie GF, D'ilario J, Costantini L, Bradford R, Schmidt B. Feasibility of comprehensive, unattended ambulatory polysomnography in school-aged children. J Clin Sleep Med. 2014 Aug 15;10(8):913-8. doi: 10.5664/jcsm.3970.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carole Marcus, M.B.B.Ch. principal investigator
University of Pennsylvania
4 sites in 2 countries: see every site and its status.
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 4 sites in 2 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 2 inclusion and 0 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 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, Canada. 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. Some participants in this study may receive a placebo. 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?
Aim 1: The primary outcome is the mean actual sleep time as measured by actigraphy, between subjects who received caffeine vs placebo. (time frame: 5-7 years). The study lists 3 primary outcomes in all. 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 NCT01020357, which also lists 4 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 5 Dec 2014.