Apnea of PrematurityPhase 2/3NCT01911182
Inhalation of Low Concentration of CO2 in Preterm Infants Not Responding to Caffeine for the Treatment of Apnea
A Phase 2/3 study testing Inhalation of low concentration of CO2 in people with Apnea of Prematurity, run by University of Manitoba at 1 site in Canada.
Trial summary
In premature infants, apnea of prematurity is one of their major clinical problems. Caffeine is currently a worldwide therapy to reduce the number and severity of these apneas. This practice has shown to be safe on cognitive and neurodevelopmental outcomes at 18 to 21 months of age. Read more about this study
- Who is it for?
- Ages 3 to 60 days
- Conditions the study is for
- Apnea of Prematurity
- What is being tested?
- Inhalation of low concentration of CO2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2011to Jul 2014
- Phase
- Phase 2/3
- 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 3 to 60 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- gestational age at birth < 33 weeks
- on caffeine treatment for apnea of prematurity at a maintenance dose of 5 mg/kg/day
- having apnea of prematurity (at least 5 self-resolved apneas or 2 apneas requiring intervention/12 hours)
Who cannot join
- on mechanical ventilation
- presence of congenital anomalies, sepsis or other known causes of apnea
- failure to obtain parental consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Controlled Trial of Inhalation of Low Concentration of CO2 in Preterm Infants Not Responding to Caffeine for the Treatment of Apnea of Prematurity
In premature infants, apnea of prematurity is one of their major clinical problems. Caffeine is currently a worldwide therapy to reduce the number and severity of these apneas. This practice has shown to be safe on cognitive and neurodevelopmental outcomes at 18 to 21 months of age. However, caffeine is not 100% effective, and may have little effect on hypoxemia and bradycardia. Infants with intractable apneas unresponsive to caffeine treatment may require endotracheal intubation and mechanical ventilation. This procedure is invasive and has been associated with complications and increased risk for chronic lung disease and adverse neurodevelopmental outcome. Therefore, an alternative treatment modality would be preferable if it would prevent the infants from requiring endotracheal intubation. The investigators have been testing the overall hypothesis that small concentrations of inhaled CO2 (~1%) are effective in treating apnea of prematurity. The investigators have completed three studies in preterm infants showing that inhalation of low concentration of CO2, in infants not on caffeine, regularize breathing and decrease apneas significantly. The effects of inhalation of CO2 in infants already on caffeine, are unknown. The hypothesis to be tested is that inhalation of low concentration CO2 (1%) will significantly reduce apnea in infants treated with caffeine. The investigators have three specific aims in this proposal. 1) the investigators want to know if the apnea rate (number of apneas of ≥5 seconds/hour) is decreased with CO2 inhalation in preterm infants already on caffeine for the treatment of apnea of prematurity; 2) the investigators want to know whether inhalation of CO2 can make breathing more regular with less apneic time and whether it decreases prolonged apneas (>20 seconds) in infants already on caffeine for the treatment of apnea of prematurity; 3) the investigators want to assess the effect of inhalation of low concentration of CO2 on the regional oxygen saturation of the brain measured by near-infrared spectroscopy (NIRS) during apneas. This is to see whether CO2, by protecting cerebral blood flow, minimizes the decrease in cerebral oxygenation during apneas. This study entails a new and possibly more physiological method of treating apneas of prematurity that can be added to the present treatment of caffeine. These two treatments together, could minimize the number and severity of apneas and possibly decrease the need for mechanical ventilation in preterm infants.
- Conditions
- Apnea of Prematurity
- Being tested
- Inhalation of low concentration of CO2
- Keywords
- apnea of prematurity, control of breathing, newborn, CO2 inhalation
- Medical subject headings
- Apnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhalation of low concentration of CO2Other
Also called Inhalatio of biological gas
Inhalation of 1% CO2 through nasal prongs
| Study group | Role | What they receive |
|---|---|---|
| Inhalation of low concentration of CO2 | Experimental | Not described Receives: Other: Inhalation of low concentration of CO2 |
| caffeine only | Active comparator | Not described Receives: Other: Inhalation of low concentration of CO2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of inhalation of low concentration of CO2 (1%) on the apnea rate (number of apneas of ≥5 seconds/hour) in preterm infants already on caffeine for the treatment of apnea of prematurity.
Measured: 3 hours
Secondary outcomes (1)
Effect of low concentration of CO2 on apneic time in seconds per hour and duration of long apneas in seconds
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study startOct 2011
- Primary completionJul 2013
- Study completionJul 2014
Why it stopped: Low recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)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 University of ManitobaThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- Manitoba Institute of Child Health
- Responsible party
- Principal investigator, Ruben Alvaro, University of Manitoba
- Investigators
- Ruben E Alvaro, MD, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911182
- Sponsor's protocol ID
- B2011:072
- Status last verified
- Feb 2015
- First submitted
- 22 Sep 2011
- Last updated
- 19 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Al-Saif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Qurashi M, Rigatto H. A randomized controlled trial of theophylline versus CO2 inhalation for treating apnea of prematurity. J Pediatr. 2008 Oct;153(4):513-8. doi: 10.1016/j.jpeds.2008.04.025. Epub 2008 Jun 4.
PubMed 18534618Al-Aif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Rigatto H. Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity. Semin Perinatol. 2001 Apr;25(2):100-6. doi: 10.1053/sper.2001.23199.
PubMed 11339662Alvaro RE, Khalil M, Qurashi M, Al-Saif S, Al-Matary A, Chiu A, Minski J, Manfreda J, Kwiatkowski K, Cates D, Rigatto H. CO(2) inhalation as a treatment for apnea of prematurity: a randomized double-blind controlled trial. J Pediatr. 2012 Feb;160(2):252-257.e1. doi: 10.1016/j.jpeds.2011.07.049. Epub 2011 Sep 9.
PubMed 21907349Schmidt B, Roberts RS, Davis P, Doyle LW; Steering Committee of the Caffeine for Apnea of Prematurity (CAP) trial. Archimedes: Does caffeine treatment for apnoea of prematurity improve neurodevelopmental outcome in later life? Arch Dis Child. 2011 Aug;96(8):784. doi: 10.1136/adc.2010.206698. Epub 2011 Mar 4. No abstract available.
PubMed 21377992Davis 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 19926098Schmidt 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 17989382Schmidt 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
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Controlled Trial of Inhalation of Low Concentration of CO2 in Preterm Infants Not Responding to Caffeine for the Treatment of Apnea of Prematurity
- ClinicalTrials.gov ID
- NCT01911182
- Acronym / sponsor ID
- B2011:072
- Conditions
- Apnea of Prematurity
- Keywords
- apnea of prematurity, control of breathing, newborn, CO2 inhalation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment rate
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- Manitoba Institute of Child Health
- Study start
- Oct 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 30 Jul 2013 (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.
In premature infants, apnea of prematurity is one of their major clinical problems. Caffeine is currently a worldwide therapy to reduce the number and severity of these apneas. This practice has shown to be safe on cognitive and neurodevelopmental outcomes at 18 to 21 months of age. However, caffeine is not 100% effective, and may have little effect on hypoxemia and bradycardia. Infants with intractable apneas unresponsive to caffeine treatment may require endotracheal intubation and mechanical ventilation. This procedure is invasive and has been associated with complications and increased risk for chronic lung disease and adverse neurodevelopmental outcome. Therefore, an alternative treatment modality would be preferable if it would prevent the infants from requiring endotracheal intubation. The investigators have been testing the overall hypothesis that small concentrations of inhaled CO2 (~1%) are effective in treating apnea of prematurity. The investigators have completed three studies in preterm infants showing that inhalation of low concentration of CO2, in infants not on caffeine, regularize breathing and decrease apneas significantly. The effects of inhalation of CO2 in infants already on caffeine, are unknown. The hypothesis to be tested is that inhalation of low concentration CO2 (1%) will significantly reduce apnea in infants treated with caffeine. The investigators have three specific aims in this proposal. 1) the investigators want to know if the apnea rate (number of apneas of ≥5 seconds/hour) is decreased with CO2 inhalation in preterm infants already on caffeine for the treatment of apnea of prematurity; 2) the investigators want to know whether inhalation of CO2 can make breathing more regular with less apneic time and whether it decreases prolonged apneas (>20 seconds) in infants already on caffeine for the treatment of apnea of prematurity; 3) the investigators want to assess the effect of inhalation of low concentration of CO2 on the regional oxygen saturation of the brain measured by near-infrared spectroscopy (NIRS) during apneas. This is to see whether CO2, by protecting cerebral blood flow, minimizes the decrease in cerebral oxygenation during apneas. This study entails a new and possibly more physiological method of treating apneas of prematurity that can be added to the present treatment of caffeine. These two treatments together, could minimize the number and severity of apneas and possibly decrease the need for mechanical ventilation in preterm infants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhalation of low concentration of CO2 | Experimental | Other: Inhalation of low concentration of CO2 |
| caffeine only | Active comparator | Other: Inhalation of low concentration of CO2 |
Who may qualify
- Ages
- 3 to 60 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- gestational age at birth < 33 weeks
- on caffeine treatment for apnea of prematurity at a maintenance dose of 5 mg/kg/day
- having apnea of prematurity (at least 5 self-resolved apneas or 2 apneas requiring intervention/12 hours)
Key exclusion criteria (3 listed)
- on mechanical ventilation
- presence of congenital anomalies, sepsis or other known causes of apnea
- failure to obtain parental consent
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 |
|---|---|---|
| Inhalation of low concentration of CO2Also: Inhalatio of biological gasInhalation of 1% CO2 through nasal prongs | Other | Inhalation of low concentration of CO2, caffeine only |
Primary outcome
Effect of inhalation of low concentration of CO2 (1%) on the apnea rate (number of apneas of ≥5 seconds/hour) in preterm infants already on caffeine for the treatment of apnea of prematurity.
Time frame: 3 hours
1 secondary outcome
Effect of low concentration of CO2 on apneic time in seconds per hour and duration of long apneas in seconds
Time frame: 3 hours
Results and safety
The study was stopped early (reason given: Low recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2015.
- Background: PubMed 18534618Al-Saif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Qurashi M, Rigatto H. A randomized controlled trial of theophylline versus CO2 inhalation for treating apnea of prematurity. J Pediatr. 2008 Oct;153(4):513-8. doi: 10.1016/j.jpeds.2008.04.025. Epub 2008 Jun 4.
- Background: PubMed 11339662Al-Aif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Rigatto H. Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity. Semin Perinatol. 2001 Apr;25(2):100-6. doi: 10.1053/sper.2001.23199.
- Background: PubMed 21907349Alvaro RE, Khalil M, Qurashi M, Al-Saif S, Al-Matary A, Chiu A, Minski J, Manfreda J, Kwiatkowski K, Cates D, Rigatto H. CO(2) inhalation as a treatment for apnea of prematurity: a randomized double-blind controlled trial. J Pediatr. 2012 Feb;160(2):252-257.e1. doi: 10.1016/j.jpeds.2011.07.049. Epub 2011 Sep 9.
- Background: PubMed 21377992Schmidt B, Roberts RS, Davis P, Doyle LW; Steering Committee of the Caffeine for Apnea of Prematurity (CAP) trial. Archimedes: Does caffeine treatment for apnoea of prematurity improve neurodevelopmental outcome in later life? Arch Dis Child. 2011 Aug;96(8):784. doi: 10.1136/adc.2010.206698. Epub 2011 Mar 4. No abstract available.
- Background: PubMed 19926098Davis 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.
- 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.
- 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.
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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.
Ruben E Alvaro, MD principal investigator
University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Inhalation of low concentration of CO2 in people with Apnea of Prematurity, run by University of Manitoba at 1 site in Canada.
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: stopped early, as of the sponsor's last update on 19 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Low recruitment rate). Results are not available in the source record.
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?
Effect of inhalation of low concentration of CO2 (1%) on the apnea rate (number of apneas of ≥5 seconds/hour) in preterm infants already on caffeine for the treatment of apnea of prematurity. (time frame: 3 hours). 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 NCT01911182, which also lists 7 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 19 Feb 2015.