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

Официальное название

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

Обзор

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".

Подробное описание

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.

Вмешательства

• Устройство continuous positive airway pressure treatment
  CPAP treatment for one year

Первичные конечные точки

• annual rate of COPD exacerbations [Срок оценки: 12 months]

Вторичные конечные точки (12)

• Annual rate of moderate to severe COPD exacerbations and severe COPD exacerbations [Срок оценки: 12 months]
• Times to the first COPD exacerbation of any severity [Срок оценки: 12 months]
• Times to the first COPD exacerbation of the first moderate or severe COPD exacerbation [Срок оценки: 12 months]
• Times to the first COPD exacerbation of the first severe COPD exacerbation [Срок оценки: 12 months]
• Annual rate of non-fatal cardiovascular events [Срок оценки: 12 months]
• Mortality rate [Срок оценки: 12 months]
• Measurement of the quality of life [Срок оценки: 12 months]
• Dyspnea [Срок оценки: 12 months]
• Functional respiratory [Срок оценки: 12 months]
• exercise capacity [Срок оценки: 12 months]
• Daytime sleepiness [Срок оценки: 12 months]
• Subjective sleep quality [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 15 центров

• Angers University Hospital — Angers
• Bordeaux University Hospital — Bordeaux
• Brest University Hospital — Brest
• AP-HP -Henri Mondor Hsopital — Créteil
• Dijon University Hospital — Dijon
• Grenoble University Hospital — Grenoble
• Le Mans Hospital — Le Mans
• Nancy University Hospital — Nancy
• … и ещё 7 центров

Идентификаторы

NCT: NCT05958563 · 49RC21_0377

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗