Clinical trial NCT05958563: Impact of Continuous Positive Airway Pressure on the Occurrence of Acute Exacerbations of COPD in Patients With COPD-OSA Overlap Syndrome (CO-OS)
Official title: Impact of Continuous Positive Airway Pressure on the Occurrence of Acute Exacerbations of COPD in Patients With COPD-OSA Overlap Syndrome (CO-OS) SLEEPOVEA
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sleep Apnea
COPD Exacerbation
Overlap Syndrome
Keywords: sleep apnea
copd
overlap syndrome
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, France
First posted: 2023-07-24
Enrollment: 500
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized control study
Primary purpose: TREATMENT

Brief summary: 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".

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.

Eligibility criteria: 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

Primary outcomes:
measure: annual rate of COPD exacerbations
timeFrame: 12 months
Secondary outcomes:
measure: Annual rate of moderate to severe COPD exacerbations and severe COPD exacerbations
timeFrame: 12 months
measure: Times to the first COPD exacerbation of any severity
timeFrame: 12 months
measure: Times to the first COPD exacerbation of the first moderate or severe COPD exacerbation
timeFrame: 12 months
measure: Times to the first COPD exacerbation of the first severe COPD exacerbation
timeFrame: 12 months
measure: Annual rate of non-fatal cardiovascular events
timeFrame: 12 months
measure: Mortality rate
timeFrame: 12 months
measure: Measurement of the quality of life
timeFrame: 12 months
measure: Dyspnea
timeFrame: 12 months
measure: Functional respiratory
timeFrame: 12 months
measure: exercise capacity
timeFrame: 12 months
measure: Daytime sleepiness
timeFrame: 12 months
measure: Subjective sleep quality
timeFrame: 12 months
measure: Arterial blood gases
timeFrame: 12 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers University Hospital
city: Bordeaux
country: France
facility: Bordeaux University Hospital
city: Brest
country: France
facility: Brest University Hospital
city: Créteil
country: France
facility: AP-HP -Henri Mondor Hsopital
city: Dijon
country: France
facility: Dijon University Hospital
city: Grenoble
country: France
facility: Grenoble University Hospital
city: Le Mans
country: France
facility: Le Mans Hospital
city: Nancy
country: France
facility: Nancy University Hospital
city: Paris
country: France
facility: AP-HP - Pitié Salpetrière Hospital
city: Paris
country: France
facility: Bichat Hospital - AP-HP
city: Poitiers
country: France
facility: Poitiers University Hospital
city: Reims
country: France
facility: Reims University Hospital
city: Rennes
country: France
facility: Polyclinique Saint Laurent
city: Strasbourg
country: France
facility: Strasbourg University Hospital
city: Toulouse
country: France
facility: Toulouse Universty Hospital
Study officials:
References: