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

Sleep Apnea Clinical Trial

— SLEEPOVEA  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05958563
• Other study ID #: 49RC21_0377
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: January 1, 2028

Study information

• Verified date: July 2023
• Source: University Hospital, Angers
• Contact: Wojciech Trzepizur, MD PhD
• Phone: +33680575272
• Email: wotrzepizur[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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".

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: January 1, 2028
• Est. primary completion date: January 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COPD Exacerbation
• Overlap Syndrome
• Sleep Apnea
• Sleep Apnea Syndromes
• Syndrome
• Undifferentiated Connective Tissue Diseases

Intervention

Device:
• continuous positive airway pressure treatment
CPAP treatment for one year

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Angers	Ministry of Health, France

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality rate	deaths	12 months
Secondary	Measurement of the quality of life	Saint George's Respiratory Questionnaire	12 months
Secondary	Dyspnea	modified Medical Research Council scale	12 months
Secondary	Functional respiratory	forced expiratory volume in one second	12 months
Secondary	exercise capacity	6 minutes walking test	12 months
Secondary	Daytime sleepiness	Epworth Sleepiness Scale	12 months
Secondary	Subjective sleep quality	Pittsburgh sleep quality index	12 months
Secondary	Arterial blood gases	Partial pressure of oxygen and carbon dioxide	12 months