Impact of Continuous Positive Airway Pressure on the Occurrence of Acute Exacerbations of COPD in Patients With COPD-OSA Overlap Syndrome (CO-OS) (SLEEPOVEA)

Impact of Continuous Positive Airway Pressure on the Occurrence of Acute Exacerbations of COPD in Patients With COPD-OSA Overlap Syndrome (CO-OS) SLEEPOVEA

Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA) are both frequent respiratory diseases with estimated prevalences between 8 and 15% of the adult population. Because of those high prevalences those two entities are often associated in same patients (1 to 4% of the general population). This association is then referred to as Overlap Syndrome (CO-OS). Data from observational studies suggest that this association may have an additive or even synergistic negative impact on patient's prognosis. Indeed, in a cohort of patients diagnosed as having a CO-OS, patients who did not receive specific treatment for OSA had a 76% increased risk of death compared to patients treated with continuous positive airway pressure (CPAP) and a 2-fold increased risk of acute COPD exacerbation. In another cohort of patients with both OSA and severe oxygen treated COPD, untreated patients for OSA had a 5-fold increased risk of death compared to patients treated with CPAP. There are strong signals from observational studies in support of a beneficial impact of CPAP therapy on respiratory outcomes in patients with CO-OS. However, those findings are not supported by any controlled study. It is difficult to directly transpose the observational data to current clinical practice in the context of the recent studies on the impact of CPAP on OSA prognosis. Indeed, data from similar observational OSA cohorts have reported a major impact of CPAP on the overall survival and cardiovascular outcomes in patients with OSA. Ten years later, this impact has not been confirmed by several randomized studies. To date, there is no consensus on a systematic screening and, if present, management of OSA in patients with COPD. The need for specific research on that field was emphasized in 2018 in an official American Thoracic Society Research Statement which recommends "randomized trials that compare clinical outcomes among patients with Overlap Syndrome whose OSA is treated to clinical outcomes among patients with Overlap Syndrome whose OSA is untreated".

Study Overview

• Status: Recruiting
• Conditions: Sleep Apnea; COPD Exacerbation; Overlap Syndrome
• Intervention / Treatment: Device: continuous positive airway pressure treatment

Detailed Description

This study is an open labeled parallel group randomized controlled trial. The patients will be recruited within the pneumology consultations of the participating centers. Patients meeting the pre-inclusion criteria and having no exclusion criteria will be included in the study and will undergo a polysomnographic sleep recording (PSG).

Patients with apnea hypopnea index (AHI) <15 / hour and/or significant central apneas (≥5 central apneas per hour of sleep) during PSG will be excluded from the study.

Patients with moderate to severe OSA (AHI ≥15 /h) and no significant central apneas will undergo baseline evaluation (ABG, 6 minute walking test, FEV1 and questionnaires) and then will be randomly assigned to receive 1 year of CPAP treatment (CPAP group) or no treatment of OSA (control group) according to a 1:1 allocation using a computer-generated randomization list stratified by site and OSA severity with permuted blocks of random sizes.

Visit at 3,6 and 9 months: the following outcomes will be assessed: COPD exacerbations (number, date and severity), cardiovascular events, death and questionnaires.

Visit at the end of the study (12 months): the following outcomes will be assessed: COPD exacerbations (number, date and severity), cardiovascular events, death, questionnaires, ABG, 6 minute walking test, FEV1.

Statistical analysis for primary and secondary outcomes will be performed on an intention to treat basis. A per-protocol analysis will be also performed in patients with an average objective CPAP use of at least 4 hours per day. Pre-specified sensitivity analysis will be conducted according to age, gender, body-mass index, OSA and COPD severity.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wojciech Trzepizur, MD PhD; Phone Number: +33680575272; Email: wotrzepizur@chu-angers.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • Angers University Hospital
    • Contact: TRZEPIZUR Wojciech; Phone Number: 02 41 35 36 95; Email: WoTrzepizur@chu-angers.fr
  • Bordeaux, France
    • Recruiting
    • Bordeaux University Hospital
    • Contact: GRASSION Léo; Phone Number: 05 57 65 63 38; Email: leo.grassion@chu-bordeaux.fr
  • Brest, France
    • Recruiting
    • Brest University Hospital
    • Contact: LE MAO Raphael; Phone Number: 02 98 34 73 47; Email: raphael.lemao@chu-brest.fr
  • Créteil, France
    • Recruiting
    • AP-HP -Henri Mondor Hsopital
    • Contact: BOYER Laurent; Phone Number: 01 49 81 26 90; Email: laurent.boyer@aphp.fr
  • Dijon, France
    • Recruiting
    • Dijon University Hospital
    • Contact: GEORGES Marjolaine; Phone Number: 0380293772; Email: marjolaine.georges@chu-dijon.fr
  • Grenoble, France
    • Recruiting
    • Grenoble University Hospital
    • Contact: PEPIN Jean-Louis; Phone Number: 0476768473; Email: jpepin@chu-grenoble.fr
  • Le Mans, France
    • Recruiting
    • Le Mans Hospital
    • Contact: GOUPIL François; Phone Number: 02 43 43 43 45; Email: fgoupil@ch-lemans.fr
  • Nancy, France
    • Recruiting
    • Nancy University Hospital
    • Contact: CHAOUAT Ari; Phone Number: 03 83 15 40 21; Email: a.chaouat@chru-nancy.fr
  • Paris, France
    • Recruiting
    • AP-HP - Pitié Salpetrière Hospital
    • Contact: PATOUT Maxime; Phone Number: 01 42 16 78 84; Email: Maxime.patout@aphp.fr
  • Paris, France
    • Recruiting
    • Bichat Hospital - AP-HP
    • Contact: FRIJA-MASSON Justine; Phone Number: 01 40 25 52 83; Email: justine.frija@aphp.fr
  • Poitiers, France
    • Recruiting
    • Poitiers University Hospital
    • Contact: BIRONNEAU Vanessa; Phone Number: 05.49.44.44.74; Email: vanessa.bironneau@chu-poitiers.fr
  • Reims, France
    • Recruiting
    • Reims University Hospital
    • Contact: LAUNOIS Claire; Phone Number: 03 26 78 76 14; Email: claunois@chu-reims.fr
  • Rennes, France
    • Recruiting
    • Polyclinique Saint Laurent
    • Contact: PRIGENT Arnaud; Phone Number: 02 99 25 65 35; Email: arnaud.prigent@hstv.fr
  • Strasbourg, France
    • Recruiting
    • Strasbourg University Hospital
    • Contact: KESSLER Romain; Phone Number: 03 69 55 06 45; Email: romain.kessler@chru-strasbourg.fr
  • Toulouse, France
    • Recruiting
    • Toulouse Universty Hospital
    • Contact: SEDKAOUI Kamila; Phone Number: 05 67 77 18 32; Email: sekaoui.k@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 40 years of age or older
• Grade of 2 or higher on the modified Medical Research Council scale (which ranges from 0 to 4, with higher grades indicating more severe dyspnea)
• A post-bronchodilator forced expiratory volume in 1 second (FEV1) of less than 70% of the predicted value, and a postbronchodilator ratio of FEV1 to forced vital capacity (FVC) of less than 0.70.
• Documented history of at least one moderate or severe COPD exacerbation during the previous year
• Clinical suspicion of OSA (based on a STOP-bang questionnaire >3),
• Have a telephone or a tablet or accept to use one during the study,
• Willing and able to comply with all study procedures,
• Subjects covered by or having the rights to medical care assurance.
• An apnea-hypopnea index [AHI], ≥15 per hour based on a full night polysomnography and no significant central apneas (<5 central apneas per hour of sleep

Exclusion Criteria:

• Severe daytime sleepiness (Epworth sleepiness Scale >14/24 and/or frequent sleepiness while driving or patient escaping a sleep-onset accident within the last 12 months),
• Severe unstable cardiovascular disease (heart failure with FEVG≤45%, recurrent cardiac arrhythmia, instable coronary heart disease or stroke),
• Patient on long-term oxygen therapy or non-invasive ventilation
• Previously documented severe hypercapnia (PaCO2 ≥ 50mm Hg)
• Previously diagnosed and treated OSA
• Any rehabilitation program or any lung volume reduction procedure planned in the oncoming year
• Pregnancy, breastfeeding
• Bad understanding of the French language,
• Other protected person according to articles L1121.7 and L1121.8 of the French Public Health Act

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP group; Continuous positive airway pressure (CPAP) for one year	Device: continuous positive airway pressure treatment; CPAP treatment for one year
No Intervention: Control group; No CPAP treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
annual rate of COPD exacerbations	COPD exacerbations will be captured using the EXACT-PRO diary. COPD exacerbations will be defined as a worsening of two or more of dyspnea, sputum purulence or sputum volume for at least two consecutive days and captured using an electronic diary (EXACT-PRO) for mild exacerbation or during clinical visits for moderate and severe exacerbations.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual rate of moderate to severe COPD exacerbations and severe COPD exacerbations	The type of treatment provided for a COPD exacerbation will determine the severity of the exacerbation. It will be categorized as mild (involving worsening of symptoms for >2 consecutive days), moderate (leading to treatment with glucocorticoids, antibiotics, or both), or severe (leading to hospital admission)	12 months
Times to the first COPD exacerbation of any severity	COPD exacerbations will be captured using the EXACT-PRO diary. COPD exacerbations will be defined as a worsening of two or more of dyspnea, sputum purulence or sputum volume for at least two consecutive days and captured using an electronic diary (EXACT-PRO) for mild exacerbation or during clinical visits for moderate and severe exacerbations.	12 months
Times to the first COPD exacerbation of the first moderate or severe COPD exacerbation	The type of treatment provided for a COPD exacerbation will determine the severity of the exacerbation. It will be categorized as mild (involving worsening of symptoms for >2 consecutive days), moderate (leading to treatment with glucocorticoids, antibiotics, or both), or severe (leading to hospital admission)	12 months
Times to the first COPD exacerbation of the first severe COPD exacerbation	The type of treatment provided for a COPD exacerbation will determine the severity of the exacerbation. It will be categorized as mild (involving worsening of symptoms for >2 consecutive days), moderate (leading to treatment with glucocorticoids, antibiotics, or both), or severe (leading to hospital admission)	12 months
Annual rate of non-fatal cardiovascular events	non-fatal myocardial infarction, non-fatal stroke, coronary artery bypass surgery, and percutaneous transluminal coronary angiography	12 months
Mortality rate	deaths	12 months
Measurement of the quality of life	Saint George's Respiratory Questionnaire	12 months
Dyspnea	modified Medical Research Council scale	12 months
Functional respiratory	forced expiratory volume in one second	12 months
exercise capacity	6 minutes walking test	12 months
Daytime sleepiness	Epworth Sleepiness Scale	12 months
Subjective sleep quality	Pittsburgh sleep quality index	12 months
Arterial blood gases	Partial pressure of oxygen and carbon dioxide	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Collaborators: Ministry of Health, France

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 9, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: sleep apnea; copd; overlap syndrome
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Respiratory Tract Diseases; Disease; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Undifferentiated Connective Tissue Diseases; Syndrome; Sleep Apnea Syndromes
• Other Study ID Numbers: 49RC21_0377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No