Chronic Obstructive Pulmonary DiseasePhase 3OSNCT01427673
Continuous Positive Airway Pressure Versus Noninvasive Ventilation in Patients With Overlap Syndrome
A Phase 3 study testing Bipap procedure in people with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea, run by United States Air Force at 1 site in United States.
Trial summary
The purpose of this study is to determine if Bipap should assume a standard-of-care role in the management of overlap syndrome. Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnea, Overlap Syndrome
- What is being tested?
- Bipap procedure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Feb 2014
- 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 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged > 35 years, the diagnosis of both OSA and COPD. OSA must have been diagnosed using an American Academy of Sleep Medicine (AASM)-protocol overnight Type I polysomnogram assessment with a resultant RDI of >5 events/hour in association with OSA-attributable diurnal symptoms.
- COPD must be diagnosed using American Thoracic Society (ATS)-protocol pulmonary function testing.
- Patients must have Global Obstructive Lung Disease (GOLD) stage II COPD FEV1/FVC < 70% predicted in conjunction with an FEV1 <80% predicted.
- The patient must have a > 10 pack years smoking history and a documented history of at least one exacerbation leading to treatment with systemic glucocorticoids or antibiotics or hospitalization within the previous year.
Who cannot join
- Significant diseases other than COPD, i.e. disease or condition which, in the opinion of the investigator, may have put the patient at risk because of participation in the study or may have influenced either the results of the study or the patients' ability to participate in the study
- Patients with a diagnosis of asthma
- Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis
- Patients with known active tuberculosis
- Patients with brittle/unstable diabetes mellitus
- Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion 1
Show all 14Show fewer
- Patients with a history of myocardial infarction within the year prior to Visit 1
- Patients with cardiac arrhythmia that required medical or surgical treatment in the 3 months prior to enrollment
- Patients who had taken an investigational drug within 30 days or 6 half-lives (whichever is greater) prior to Visit 1
- Use of systemic corticosteroid medication at unstable doses (i.e., less than 6 weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day or 20 mg every other day
- Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives).
- Patients with any respiratory infection or COPD exacerbation in the 4 weeks prior to Visit 1 or during the run-in period should have been postponed. In the case of a respiratory infection or COPD exacerbation during the run-in period, the run-in period could have been extended up to 4 weeks
- Patients who, during their CPAP titration study are found to require such excessive CPAP pressures as to mandate a Bipap titration
- Patients with either Cheyne-stokes respiration noted on PSG assessment or a central sleep apnea with an associated central event index > 5 events/hour (using AASM central apnea/hypopnea scoring criteria)
Trial locations and contacts
1 site in 1 country.
United States1 site
Wright-Patterson Medical Center
Wpafb, Ohio, 45433
Patrick F Allan, MD
About this study
Official title: Phase III Single-blind Randomized Controlled Trial of Bipap Versus CPAP in Overlap Syndrome
The purpose of this study is to determine if Bipap should assume a standard-of-care role in the management of overlap syndrome.
Read the detailed description
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death worldwide. Acute exacerbations of COPD (AECOPD), in particular, serve as marker of an accelerated disease course and thus herald an increased risk of not only repetitive AECOPD episodes but also deteriorating pulmonary function and death (2). Obstructive sleep apnea (OSA), when it occurs in combination with COPD, is an increasingly recognized contributor to AECOPD episodes. OSA consists of repetitive sleep-related partial loss of airway caliber arising from increased transmural pressures which favor luminal collapse. OSA is estimated to afflict 4 to 9% of the populations, a prevalence which is anticipated to climb hand-in-hand with the rising incidence of obesity.
The combination of the two disorders, which has been arbitrarily labeled as Overlap Syndrome (OS), has been linked with greater elevations in arterial carbon dioxide tensions and pulmonary vascular resistance and lower arterial oxygen tensions than is seen with either of its component disorders in isolation. Elevated pulmonary artery pressures may progress to cause cor pulmonale, a process whereby compensatory right ventricle remodeling, hypertrophy, and eventually, florid heart failure. In the setting of OSA, the therapeutic gold standard is nightly continuous positive airway pressure (CPAP). Essentially, CPAP machines function by administering a single continuous positive pressure airflow to the person's airway via an appropriately fitted nasal mask. The applied pressure stents open partially occluded airway segments during sleep. Though effective in OSA and OS, it is increasingly realized that for OS patients there may exist a reduction not only in airway patency but also in ventilatory drive when sleeping such that means to augment per breath volumes may attain incremental benefits to the use of CPAP alone. Although CPAP is ineffective in COPD, Bipap has shown benefit suggesting that patient with OSA and COPD may derive an improvement in health-related outcomes by using a ventilation modality which addresses both of the underlying conditions.
Bipap functions by combining the single flow in CPAP with a second inspiratory pressure assist which not only overcomes sleep-related airway resistance but also increases the magnitude of each breath resulting in lower diurnal carbon dioxide tensions and pulmonary artery pressures. Bipap may harbor a mortality benefit in COPD; but the study results are conflicting. It is unclear if Bipap is more effective at treating OSA than usual CPAP. However, it is in the setting of OS that Bipap may assume a prominent role through its ability to address both disorders; CPAP for the OSA portion and an inspiratory pressure assist to ameliorate the COPD piece. Thus far no study has been conducted to address whether OS may derive a particular benefit from Bipap or, more specifically, examine whether Bipap may diminish the risk of AECOPD, or heart failure-related hospitalizations.
- Being tested
- Bipap procedure
- Keywords
- Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnea, Overlap Syndrome, COPD, OSA
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bipap procedureProcedure or surgery
Overlap patients randomized to Bipap titrated per AASM guidleines with an IPAP to EPAP diffrence of at least 8 cm H2O.
| Study group | Role | What they receive |
|---|---|---|
| CPAP Procedure control group | Active comparator | Overlap patients randomly assigned to the CPAP titrated per AASM guidelines. Receives: Procedure: Bipap procedure |
| Bipap procedure group | Experimental | Overlap patients randomized to Bipap titrated per AASM guidleines with an IPAP to EPAP diffrence of at least 8 cm H2O. Receives: Procedure: Bipap procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
The co-primary AECOPD and heart failure (AHF) outcome will be subdivided (see below).
Number of patients with events:
Occurrence of at least 1 COPD exacerbation; Occurrence of at least 1 COPD exacerbation leading to hospitalization; Occurrence of premature discontinuation of CPAP or Bipap; Occurrence of at least one clinician-diagnosed acute or acute-on-chronic heart failure event; Occurrence of arrythmogenic events requiring either the outpatient initiation of a new non-B blocker antiarrythmic agent or hospitalization to treat an arrythmia;
Number of events (stratified by number of events over the 12 month period)will also be measured.
Measured: 12 month intervention period
Secondary outcomes (2)
Difference in exertional and questionnaire-based quality-of-life indicators
Difference from baseline in 6 minute walk test distance, oxygen walk test-assessed supplemental oxygen requirements, St. George's Respiratory Questionnaire (SGRQ) and UCSD Shortness of breath questionnaire scores.
Mortality (subdivided into the following) Cancer, No. CVS, No. Pulmonary, No. Other, No. All causes, No.
Mean and median nightly number of hours used for each NIV modality
Measured: 12 month intervention period
Safety outcome measures
- Serious adverse events
- Adverse events leading to treatment discontinuation
- Treatment-related adverse events
- Major adverse cardiovascular events (MACE) during treatment*
- All-cause mortality with onset of fatal AECOPD during treatment with study intervention + 30 days *Included fatal cardiac disorders, fatal vascular disorders, sudden death, cardiac death, sudden cardiac death, serious adverse events (fatal and non-fatal) from myocardial infarction, and stroke.
Measured: 12 month intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2013 (estimated)
- Study completionFeb 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- 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
- Single blind
- Who is masked
- Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- United States Air Force
- Sponsor type
- US federal agency
- Collaborators
- Landstuhl Regional Medical Center, Good Samaritan Hospital, Dayton Respiratory Center, Tripler Army Medical Center
- Responsible party
- Principal investigator, Patrick F. Allan, United States Air Force
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01427673
- Sponsor's protocol ID
- USAF
- Acronym
- OS
- Status last verified
- Aug 2011
- First submitted
- 29 Aug 2011
- Last updated
- 1 Sep 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Lee R. McNicholas WT. Obstructive sleep apnea in chronic obstructive pulmonary disease patients. Current Opinion in Pulmonary Medicine. 17(2):79-83, 2011. Hiestand D. Phillips B. The overlap syndrome: chronic obstructive pulmonary disease and obstructive sleep apnea. Critical Care Clinics. 24(3):551-63, vii, 2008. Owens RL. Malhotra A. Sleep-disordered breathing and COPD: the overlap syndrome. Respiratory Care. 55(10):1333-44; discussion 1344-6, 2010. Marin JM. Soriano JB. Carrizo SJ. Boldova A. Celli BR. Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea The Overlap Syndrome. Am J Respir Crit Care Med Vol 182. pp 325-331, 2010.
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Single-blind Randomized Controlled Trial of Bipap Versus CPAP in Overlap Syndrome
- ClinicalTrials.gov ID
- NCT01427673
- Acronym / sponsor ID
- OS / USAF
- Keywords
- Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnea, Overlap Syndrome, COPD, OSA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- United States Air ForceUS federal agency
- Collaborators
- Landstuhl Regional Medical Center, Good Samaritan Hospital, Dayton Respiratory Center, Tripler Army Medical Center
- Study start
- Dec 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Feb 2014 (estimated)
- First posted
- 1 Sep 2011 (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.
The purpose of this study is to determine if Bipap should assume a standard-of-care role in the management of overlap syndrome.
Detailed description
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death worldwide. Acute exacerbations of COPD (AECOPD), in particular, serve as marker of an accelerated disease course and thus herald an increased risk of not only repetitive AECOPD episodes but also deteriorating pulmonary function and death (2). Obstructive sleep apnea (OSA), when it occurs in combination with COPD, is an increasingly recognized contributor to AECOPD episodes. OSA consists of repetitive sleep-related partial loss of airway caliber arising from increased transmural pressures which favor luminal collapse. OSA is estimated to afflict 4 to 9% of the populations, a prevalence which is anticipated to climb hand-in-hand with the rising incidence of obesity.
The combination of the two disorders, which has been arbitrarily labeled as Overlap Syndrome (OS), has been linked with greater elevations in arterial carbon dioxide tensions and pulmonary vascular resistance and lower arterial oxygen tensions than is seen with either of its component disorders in isolation. Elevated pulmonary artery pressures may progress to cause cor pulmonale, a process whereby compensatory right ventricle remodeling, hypertrophy, and eventually, florid heart failure. In the setting of OSA, the therapeutic gold standard is nightly continuous positive airway pressure (CPAP). Essentially, CPAP machines function by administering a single continuous positive pressure airflow to the person's airway via an appropriately fitted nasal mask. The applied pressure stents open partially occluded airway segments during sleep. Though effective in OSA and OS, it is increasingly realized that for OS patients there may exist a reduction not only in airway patency but also in ventilatory drive when sleeping such that means to augment per breath volumes may attain incremental benefits to the use of CPAP alone. Although CPAP is ineffective in COPD, Bipap has shown benefit suggesting that patient with OSA and COPD may derive an improvement in health-related outcomes by using a ventilation modality which addresses both of the underlying conditions.
Bipap functions by combining the single flow in CPAP with a second inspiratory pressure assist which not only overcomes sleep-related airway resistance but also increases the magnitude of each breath resulting in lower diurnal carbon dioxide tensions and pulmonary artery pressures. Bipap may harbor a mortality benefit in COPD; but the study results are conflicting. It is unclear if Bipap is more effective at treating OSA than usual CPAP. However, it is in the setting of OS that Bipap may assume a prominent role through its ability to address both disorders; CPAP for the OSA portion and an inspiratory pressure assist to ameliorate the COPD piece. Thus far no study has been conducted to address whether OS may derive a particular benefit from Bipap or, more specifically, examine whether Bipap may diminish the risk of AECOPD, or heart failure-related hospitalizations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPAP Procedure control group | Active comparator | Procedure: Bipap procedureOverlap patients randomly assigned to the CPAP titrated per AASM guidelines. |
| Bipap procedure group | Experimental | Procedure: Bipap procedureOverlap patients randomized to Bipap titrated per AASM guidleines with an IPAP to EPAP diffrence of at least 8 cm H2O. |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged > 35 years, the diagnosis of both OSA and COPD. OSA must have been diagnosed using an American Academy of Sleep Medicine (AASM)-protocol overnight Type I polysomnogram assessment with a resultant RDI of >5 events/hour in association with OSA-attributable diurnal symptoms.
- COPD must be diagnosed using American Thoracic Society (ATS)-protocol pulmonary function testing.
- Patients must have Global Obstructive Lung Disease (GOLD) stage II COPD FEV1/FVC < 70% predicted in conjunction with an FEV1 <80% predicted.
- The patient must have a > 10 pack years smoking history and a documented history of at least one exacerbation leading to treatment with systemic glucocorticoids or antibiotics or hospitalization within the previous year.
Key exclusion criteria (14 listed)
- Significant diseases other than COPD, i.e. disease or condition which, in the opinion of the investigator, may have put the patient at risk because of participation in the study or may have influenced either the results of the study or the patients' ability to participate in the study
- Patients with a diagnosis of asthma
- Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis
- Patients with known active tuberculosis
- Patients with brittle/unstable diabetes mellitus
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 |
|---|---|---|
| Bipap procedureOverlap patients randomized to Bipap titrated per AASM guidleines with an IPAP to EPAP diffrence of at least 8 cm H2O. | Procedure or surgery | Bipap procedure group, CPAP Procedure control group |
Primary outcome
The co-primary AECOPD and heart failure (AHF) outcome will be subdivided (see below).
Time frame: 12 month intervention period
Number of patients with events: Occurrence of at least 1 COPD exacerbation; Occurrence of at least 1 COPD exacerbation leading to hospitalization; Occurrence of premature discontinuation of CPAP or Bipap; Occurrence of at least one clinician-diagnosed acute or acute-on-chronic heart failure event; Occurrence of arrythmogenic events requiring either the outpatient initiation of a new non-B blocker antiarrythmic agent or hospitalization to treat an arrythmia; Number of events (stratified by number of events over the 12 month period)will also be measured.
2 secondary outcomes
Difference in exertional and questionnaire-based quality-of-life indicators
Time frame: 12 month intervention period
Safety outcome measures
Time frame: 12 month intervention period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2011.
- Results publicationLee R. McNicholas WT. Obstructive sleep apnea in chronic obstructive pulmonary disease patients. Current Opinion in Pulmonary Medicine. 17(2):79-83, 2011. Hiestand D. Phillips B. The overlap syndrome: chronic obstructive pulmonary disease and obstructive sleep apnea. Critical Care Clinics. 24(3):551-63, vii, 2008. Owens RL. Malhotra A. Sleep-disordered breathing and COPD: the overlap syndrome. Respiratory Care. 55(10):1333-44; discussion 1344-6, 2010. Marin JM. Soriano JB. Carrizo SJ. Boldova A. Celli BR. Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea The Overlap Syndrome. Am J Respir Crit Care Med Vol 182. pp 325-331, 2010.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bipap procedure in people with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea, run by United States Air Force at 1 site in United States.
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 4 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 1 Sep 2011. 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 United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patrick F Allan, MD (937-608-7958, sallanrj@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The co-primary AECOPD and heart failure (AHF) outcome will be subdivided (see below). (time frame: 12 month intervention period). 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 NCT01427673, which also lists 1 linked publication.
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 1 Sep 2011.