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Chronic Obstructive Pulmonary DiseaseNCT05623709

Health Outcomes With CPAP or NIV in Patients With COPD and a Sleep Related Breathing Disorder

An observational study of Chronic Obstructive Pulmonary Disease and Sleep Related Hypoventilation, run by University of Alberta at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease affecting an estimated 1 in 10 Canadians. Symptoms include persistent shortness of breath, cough and sputum production. The symptoms can be serious when people with COPD experience a flare of their disease and may lead to hospitalization or death. Read more about this study

Who is it for?
Ages 40 years and olderHealthy volunteers can take part
What is being tested?
Positive airway pressure with continuous positive airway pressure or noninvasive ventilation
Type of treatment
Medical device
How many people
11 participants
Where
1 siteCanada
Study dates
26 Jul 2022to 22 Mar 2024
Phase
Observational
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 40 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: The study setting are people living in Alberta receiving care by an adult respirologist who undergo sleep diagnostic testing, consent to contact for research at a participating site, are eligible for the study after a brief chart review, and who subsequently consent to be involved in the study. The start date for CPAP or NIV will need to be within the study period although it will not need to be after the date of sleep diagnostic testing in order to allow patients started on NIV in hospital who subsequently undergo sleep diagnostic testing to be eligible. Polysomnograms for eligible patients will be completed by sleep laboratories operating within Alberta Health Services within the public health care system. Home sleep apnea tests are performed by both private and public facilities within Alberta and both sites of testing will be considered adequate for patient inclusion in the study if that is the sole form of sleep diagnostic testing requested by the treating respirologist.

Who may be able to join

  • Consenting adults who have completed polysomnography at the University of Alberta Sleep Disorders Laboratory in Edmonton, Alberta, Canada.
  • Naïve to CPAP or NIV therapy or have use of CPAP or NIV <4 weeks in the past
  • Diagnosed with COPD by a respirologist and has fixed airflow obstruction on spirometry (i.e., post-bronchodilator FEV1/FVC <LLN on spirometry or FEV1/FVC <0.70 if the LLN is not provided)
  • Diagnosed with a SRBD for which CPAP or NIV are commonly prescribed, as defined below; some of the patients with mild SRBD or a SRBD suspected to be secondary to COPD rather than OSA (e.g. mild OSA, sustained hypercarbia, hypoxemia etc) may not be prescribed CPAP or NIV at the treating physician's discretion
  • OSA will be defined as a predominantly obstructive apnea-hypopnea index (AHI) ≥5 events/hr of sleep on sleep diagnostic testing in the presence of symptoms/relevant comorbidities or an AHI ≥15 events/hr irrespective of symptoms. If home sleep apnea testing was used in place of polysomnography, the respiratory event index (REI) will be a surrogate of AHI.
  • Hypoventilation will be defined by polysomnography criteria as a sustained elevation in the TcCO2 to be >55 mmHg for ≥10 min or a rise in TcCO2 by >10 mmHg to a value >50 mmHg for ≥10 min. If an arterial blood gas is available, sustained hypercapnia as defined by arterial carbon dioxide oxygen tension (PaCO2) >45 mmHg or serum bicarbonate (HCO3) ≥27 mmol/L while medically stable will be reported.

Who cannot join

  • Significant lung disease in addition to COPD
  • Neuromuscular disease including diaphragmatic paralysis
  • Dementia
  • Treatment with CPAP or NIV for >4 weeks prior to study eligibility.
  • Refusal to participate
  • Inability to consent in English and do not have an interpreter readily available
  • Current diagnosis of an active malignancy
  • Central sleep apnea as the indication for PAP treatment. Central sleep apnea will be defined as a central hypopnea index ≥5 events/hr of sleep on polysomnography and the number of central apneas and/or central hypopneas is >50% of the AHI with or without Cheyne-Stokes breathing

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • University of Alberta

    Edmonton, Alberta, T6G2G3

Other trials in Canada

About this study

Official title: Health Outcomes Following Treatment With Continuous Positive Airway Pressure or Noninvasive Ventilation in Patients With Chronic Obstructive Pulmonary Disease and a Sleep Related Breathing Disorder

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease affecting an estimated 1 in 10 Canadians. Symptoms include persistent shortness of breath, cough and sputum production. The symptoms can be serious when people with COPD experience a flare of their disease and may lead to hospitalization or death. Improving other conditions that affect COPD control is one way to improve the health of people with COPD. Obstructive sleep apnea (OSA) is the most common breathing problem during sleep, and commonly co-exists with COPD. Although diagnosing and treating OSA is encouraged, it has not been highlighted in guidelines that recommend ideal COPD care. People with COPD and OSA have lower sleep quality and lower oxygen levels during sleep compared to people with OSA. Despite these differences, treatment of OSA in people with COPD is modeled after treatment of OSA in the general population, generally using treatment with continuous positive airway pressure (CPAP) with the possible addition of oxygen through the CPAP machine. There are few studies looking at other types of treatment including noninvasive ventilation (NIV) in people with COPD and OSA. The majority of studies of NIV in COPD has been for people with other reasons to use NIV including acute respiratory failure or chronic hypercarbic respiratory failure and did not include people with risk factors for OSA or who had undergone overnight sleep studies.

In Alberta, NIV is provided province wide for people who have both OSA who do not meet certain physiologic targets in their oxygen levels or breathing patterns after CPAP is applied on an overnight sleep study. NIV is provided preferentially to CPAP and oxygen, providing an opportunity to look at health outcomes when NIV is used instead of CPAP for the treatment of patients with COPD. Through this study, we will measure whether people with COPD and a sleep related breathing disorder such as OSA have fewer severe flares of COPD after starting CPAP or NIV. We will evaluate whether the number of Emergency Department visits, hospitalizations or deaths lowers after starting CPAP or NIV.

Read the detailed description

Chronic obstructive pulmonary disease is a common chronic lung disease affecting more than 10% of Canadians. Patients with COPD have significant morbidity from the disease as almost 60% of Albertans living with COPD were hospitalized between 2012-2014. Sleep related breathing disorders (SRBD) are a common comorbidity of COPD, and contribute to the morbidity associated with COPD. The most common SRBD is OSA. It is estimated that 1.0-3.6% of Canadians are affected by both OSA and COPD. People with COPD and OSA have lower sleep quality, lower oxygen saturations and greater nocturnal oxygen desaturations when their sleep is compared to people with OSA. Observational studies suggest that patients with OSA and COPD have a higher risk of hospitalization, exacerbation of COPD, or death; however, the evidence to support the assessment and management of OSA improving COPD health outcomes has not been considered substantial enough to justify inclusion in COPD guidelines. Other SRBDs that may impact patients with COPD are sleep-related hypoventilation as a consequence of obesity, or central sleep apnea as a consequence of cardiac disease, stroke or use of opioids; however, these are less common and less studied types of SRBD within sleep literature.

Two treatments that are commonly prescribed for SRBD are CPAP or NIV. In patients with OSA, CPAP improves quality of life, daytime sleepiness, and blood pressure control. In patients with COPD who have OSA, observational studies suggest that CPAP use is associated with survival, with the duration of CPAP use per night lowering mortality in a dose dependent manner, an increased time to first moderate-severe COPD exacerbation and fewer hospitalizations related to exacerbations of COPD. The association of decreased health care utilization with CPAP is greater in patients with a higher COPD complexity and number of comorbidities, indicating those who are the sickest may derive the most harm from untreated disease. NIV is better tolerated than CPAP in some patients with OSA; yet, there have been only a few studies evaluating its use for a SRBD in COPD. Further work in this area is critically important as the indications for use of NIV are expanding among patients with COPD.

We are uniquely positioned to complete this study as NIV is provided province-wide in Alberta and patient health outcomes are available in provincial databases. In addition, within the provincial titration protocol for polysomnography, NIV is provided preferentially over CPAP with oxygen, differentiating the management of these patients from the titration protocols used in other studies.

Through this study, we will explore whether treatment with NIV or CPAP for a SRBD in patients with COPD results in fewer moderate-severe exacerbations of COPD and whether the use of these devices have an impact on health care utilization and mortality. In a subgroup analysis, we will explore whether NIV use results in similar outcomes as CPAP, and account for differences in disease severity in this comparison. Adherence with these CPAP or NIV will also be summarized. The results from this study will inform regional care as well as provide insight into the roles of CPAP and NIV in the treatment of SRBD in patients with COPD.

Sample size:

59% of Albertans with COPD experience an exacerbation within a 2 year period; however, a conservative estimate of 50% will be used for the power calculation. A clinically significant difference in COPD exacerbations is estimated to be 25%. An estimated standard deviation of 8 patients hospitalized per 2 years was estimated (variance 64). Given that the exposure group will be stratified by use of CPAP or NIV in subgroup analysis, a 2:1 proportion for the exposure to comparison group was utilized and the exposure arm will be composed of equal proportions of patients prescribed CPAP or NIV. A 10% drop out rate is anticipated.

Primary hypothesis: Null hypothesis (H0): CPAP or NIV is equivalent to no therapy; Alternate hypothesis (H1): CPAP or NIV is better than no therapy

Secondary hypothesis: Null hypothesis (H0): NIV is equivalent to CPAP; Alternate hypothesis (H1): NIV is better than CPAP

For the primary hypothesis, these estimates suggest that a sample size of 165 patients is required (n=110 patients in the exposure arm and 55 patients in the control arm). For the secondary hypothesis, it is not anticipated that a large difference between CPAP or NIV will be observed; however, the subgroup analysis of the primary outcome will be powered to detect a 25% difference between intervention with CPAP or NIV.

Being tested
Positive airway pressure with continuous positive airway pressure or noninvasive ventilation
Keywords
continuous positive airway pressure, bilevel positive airway pressure, noninvasive ventilation
Medical subject headings
Pulmonary Disease, Chronic Obstructive, Sleep Apnea, Obstructive, Hypoventilation

What participants receive

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

  • Positive airway pressure with continuous positive airway pressure or noninvasive ventilationDevice

    Also called CPAP, NIV, PAP treatment

    CPAP or NIV prescribed by the treating respirologist for long-term use at home

Study groups in NCT05623709
Study groupRoleWhat they receive
COPD and SRBD prescribed NIV or CPAPGroup 1a: (n=55) Adults with a SRBD and COPD who are newly prescribed NIV treatment within the study period. Group 1b: (n=55) Adults with a SRBD and COPD who are newly prescribed CPAP treatment within the study period.
Receives: Device: Positive airway pressure with continuous positive airway pressure or noninvasive ventilation
COPD controls not prescribed CPAP or NIVGroup 2: COPD controls without a SRBD: (n=55) Adults with COPD who undergo sleep diagnostic testing and who are not recommended to start CPAP or NIV

What is being measured

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

  1. Proportion of patients with moderate-severe exacerbations of COPD (Emergency Department visit for COPD) in the 2 years following initiation of CPAP or NIV compared to the 2 years prior

    [stratified by intervention with CPAP or NIV]

    Measured: 2 years

Secondary outcomes (7)

  1. Proportion of patients with severe exacerbation of COPD (hospitalization/intensive care unit admission for COPD) in the 2 years following initiation of CPAP or NIV compared to the 2 years prior

    [stratified by intervention with CPAP or NIV]

    Measured: 2 years

  2. Mean difference in the number of days hospitalized in the 2 years after the date of CPAP or NIV initiation or date of sleep diagnostic testing compared to the 2 years prior

    [stratified by intervention with CPAP or NIV] [stratified by all-cause, stroke, cardiovascular, exacerbation of COPD or respiratory cause] Total number of days hospitalized [stratified by number of events/year]

    Measured: 2 years

  3. Mean difference in hospitalizations/intensive care unit admissions for severe exacerbations of COPD in the 2 years after the date of CPAP or NIV initiation or date of sleep diagnostic testing compared to the 2 years prior

    [stratified by intervention with CPAP or NIV] Number of events [stratified by number of events/year] Time to event

    Measured: 2 years

  4. Mean difference in Emergency Department visits for moderate-severe exacerbations of COPD in the 2 years after the date of CPAP or NIV initiation or date of sleep diagnostic testing compared to the 2 years prior

    [stratified by intervention with CPAP or NIV] Number of events [stratified by number of events/year] Time to event

    Measured: 2 years

  5. Composite outcome of Emergency Department visits or hospitalizations following the date of NIV or CPAP initiation or date of sleep diagnostic testing

    [stratified by all-cause, stroke, cardiovascular, exacerbation of COPD or respiratory cause] [stratified by intervention with CPAP or NIV]

    Measured: 2 years

  6. Mortality following the start of NIV or CPAP or following the date of sleep diagnostic testing

    [stratified by all-cause, stroke, cardiovascular, exacerbation of COPD or respiratory cause] [stratified by intervention with CPAP or NIV]

    Measured: 2 years

  7. Mean and median hours of use of CPAP or NIV in hours/day

    [Stratified by intervention with CPAP or NIV]

    Measured: 2 years

Timeline

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

  1. First posted21 Nov 2022
  2. Study start26 Jul 2022
  3. Primary completion22 Mar 2024
  4. Study completion22 Mar 2024

Why it stopped: Recruitment difficulties

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05623709
Sponsor's protocol ID
Pro00118055
Status last verified
Mar 2024
First submitted
11 Nov 2022
Last updated
26 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No: Given that this is a phase IV clinical trial, the information will be disseminated through publication. Requests for IPD data from this study will need to go through institutional ethics review prior to use for a secondary purpose.

Publications

  • Shawon MS, Perret JL, Senaratna CV, Lodge C, Hamilton GS, Dharmage SC. Current evidence on prevalence and clinical outcomes of co-morbid obstructive sleep apnea and chronic obstructive pulmonary disease: A systematic review. Sleep Med Rev. 2017 Apr;32:58-68. doi: 10.1016/j.smrv.2016.02.007. Epub 2016 Mar 2.

    PubMed 28169105

  • Donovan LM, Feemster LC, Udris EM, Griffith MF, Spece LJ, Palen BN, He K, Parthasarathy S, Strohl KP, Kapur VK, Au DH. Poor Outcomes Among Patients With Chronic Obstructive Pulmonary Disease With Higher Risk for Undiagnosed Obstructive Sleep Apnea in the LOTT Cohort. J Clin Sleep Med. 2019 Jan 15;15(1):71-77. doi: 10.5664/jcsm.7574.

    PubMed 30621828

  • 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. 2010 Aug 1;182(3):325-31. doi: 10.1164/rccm.200912-1869OC. Epub 2010 Apr 8.

    PubMed 20378728

  • Criner GJ, Bourbeau J, Diekemper RL, Ouellette DR, Goodridge D, Hernandez P, Curren K, Balter MS, Bhutani M, Camp PG, Celli BR, Dechman G, Dransfield MT, Fiel SB, Foreman MG, Hanania NA, Ireland BK, Marchetti N, Marciniuk DD, Mularski RA, Ornelas J, Road JD, Stickland MK. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015 Apr;147(4):894-942. doi: 10.1378/chest.14-1676.

    PubMed 25321320

  • O'Donnell DE, Aaron S, Bourbeau J, Hernandez P, Marciniuk D, Balter M, Ford G, Gervais A, Goldstein R, Hodder R, Maltais F, Road J; Canadian Thoracic Society. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease--2003. Can Respir J. 2003 May-Jun;10 Suppl A:11A-65A. doi: 10.1155/2003/567598. English, French.

    PubMed 12861361

  • Laratta CR, Ayas NT, Povitz M, Pendharkar SR. Diagnosis and treatment of obstructive sleep apnea in adults. CMAJ. 2017 Dec 4;189(48):E1481-E1488. doi: 10.1503/cmaj.170296. No abstract available.

    PubMed 29203617

  • Machado MC, Vollmer WM, Togeiro SM, Bilderback AL, Oliveira MV, Leitao FS, Queiroga F Jr, Lorenzi-Filho G, Krishnan JA. CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD. Eur Respir J. 2010 Jan;35(1):132-7. doi: 10.1183/09031936.00192008. Epub 2009 Jul 2.

    PubMed 19574323

  • Stanchina ML, Welicky LM, Donat W, Lee D, Corrao W, Malhotra A. Impact of CPAP use and age on mortality in patients with combined COPD and obstructive sleep apnea: the overlap syndrome. J Clin Sleep Med. 2013 Aug 15;9(8):767-72. doi: 10.5664/jcsm.2916.

    PubMed 23946706

  • Singh G, Agarwal A, Zhang W, Kuo YF, Sultana R, Sharma G. Impact of PAP therapy on hospitalization rates in Medicare beneficiaries with COPD and coexisting OSA. Sleep Breath. 2019 Mar;23(1):193-200. doi: 10.1007/s11325-018-1680-0. Epub 2018 Jun 22.

    PubMed 29931497

  • Kaminska M, Rimmer KP, McKim DA, Nonoyama M, Giannouli E, Morrison Debra L, et al. Long-term non-invasive ventilation in patients with chronic obstructive pulmonary disease (COPD): 2021 Canadian Thoracic Society Clinical Practice Guideline update. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine. 2021;5(3):160-83.

  • Leung C, Bourbeau J, Sin DD, Aaron SD, FitzGerald JM, Maltais F, Marciniuk DD, O'Donnell D, Hernandez P, Chapman KR, Walker B, Road JD, Zheng L, Zou C, Hogg JC, Tan WC; CanCOLD Collaborative Research Group. The Prevalence of Chronic Obstructive Pulmonary Disease (COPD) and the Heterogeneity of Risk Factors in the Canadian Population: Results from the Canadian Obstructive Lung Disease (COLD) Study. Int J Chron Obstruct Pulmon Dis. 2021 Feb 12;16:305-320. doi: 10.2147/COPD.S285338. eCollection 2021.

    PubMed 33603357

  • Canadian Institute for Health Information. COPD in Alberta: Examining the Characteristics and Health Care Use of High Users. Ottawa, ON: CIHI; 2017.

  • Ishak A, Ramsay M, Hart N, Steier J. BPAP is an effective second-line therapy for obese patients with OSA failing regular CPAP: A prospective observational cohort study. Respirology. 2020 Apr;25(4):443-448. doi: 10.1111/resp.13674. Epub 2019 Aug 12.

    PubMed 31407464

  • Murphy PB, Arbane G, Ramsay M, Suh ES, Mandal S, Jayaram D, Leaver S, Polkey MI, Hart N. Safety and efficacy of auto-titrating noninvasive ventilation in COPD and obstructive sleep apnoea overlap syndrome. Eur Respir J. 2015 Aug;46(2):548-51. doi: 10.1183/09031936.00205714. Epub 2015 Jun 25. No abstract available.

    PubMed 26113686

  • Duiverman ML, Wijkstra PJ. Long-Term Noninvasive Ventilation in COPD: Is High-Intensity NIV The Way To Go? Chronic Obstr Pulm Dis. 2015 Dec 14;3(1):378-381. doi: 10.15326/jcopdf.3.1.2015.0179. No abstract available.

    PubMed 28848859

Questions about this trial

What is this clinical trial studying?

An observational study of Chronic Obstructive Pulmonary Disease and Sleep Related Hypoventilation, run by University of Alberta 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 6 inclusion and 8 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 26 Mar 2024. 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.

Are results available for this study?

The study was stopped early (reason given: Recruitment difficulties). 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?

Proportion of patients with moderate-severe exacerbations of COPD (Emergency Department visit for COPD) in the 2 years following initiation of CPAP or NIV compared to the 2 years prior (time frame: 2 years). 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 NCT05623709, which also lists 23 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 26 Mar 2024.

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