Comparing Two Types of Breathing Support in People With COPD, High Carbon Dioxide Levels, and Sleep Apnea

Purpose: This pilot randomized controlled trial (RCT) compares two ventilation strategies delivered via bilevel positive airway pressure (BiPAP) in patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS) with chronic stable hypercapnia. The two strategies are an OSA-targeted approach (low pressure support, functionally equivalent to continuous positive airway pressure [CPAP]) and a high-intensity ventilation approach (high pressure support targeting correction of alveolar hypoventilation).

Justification: Co-existence of COPD and OSA, termed overlap syndrome (OVS), is estimated to affect 1% of the general population, and approximately 40% of these patients develop chronic stable hypercapnia, which is associated with overall poor prognosis. OVS patients have significantly higher overall and cardiovascular mortality than patients with COPD or OSA alone. Despite the high prevalence and poor prognosis of OVS, limited research has been done to optimize therapy. In particular, OVS patients have been systematically excluded from clinical trials for both COPD and obesity hypoventilation syndrome (OHS) populations. Clinicians are currently left to extrapolate treatment recommendations for OVS from two related but contradictory evidence bases. The American Thoracic Society (ATS), Canadian Thoracic Society (CTS), and European Respiratory Society (ERS) guidelines for chronic stable hypercapnic COPD recommend non-invasive ventilation (NIV) with high-intensity settings, while ATS guidelines for OHS recommend CPAP for patients with coexisting severe OSA. A direct comparison of ventilation strategies in OVS with chronic stable hypercapnia has been identified as a high research priority by the ATS research statement on OVS. This pilot trial addresses that evidence gap and will inform the design of a future large multi-center RCT.

Hypothesis: Investigators hypothesize that the OSA-targeted and high-intensity ventilation strategies will demonstrate equivalent efficacy in correcting hypercapnia in patients with OVS.

Objectives: The primary objective is determine changes in CO₂ with an OSA-targeted ventilation strategy, with comparison to high-intensity ventilation over a 12-month follow-up period. The secondary objective will be to evaluate feasibility of a larger multi-site RCT. This would include participant recruitment metrics (number of patients screened and enrolled), protocol completion rates (including adherence to data collection instruments), and patient-reported measures such as quality of life (COPD- and sleep-specific questionnaires), NIV side effects, and adherence to therapy (e.g. % of patients fulfilling criteria of >4 hours/night).

Research Design: Investigators will conduct an open-label, parallel-group, single-center, pilot RCT. Patient inclusion criteria: 1) COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) C or D; 2) FEV1 < 50% predicted; 3) daytime PvCO2 (venous blood gas) on room air >50 mmHg; 4) OSA with moderate to severe obstructive AHI >=15event/hr based on PSG; 5) BMI >=30 kg/m2 6) Age >=40 years

Two arms (randomization to OSA-targeted vs high-intensity ventilation in a ratio of 1:1) will be compared. A titration polysomnography (PSG) will be conducted with the fitted mask to determine optimal device settings within 4 weeks of the baseline visit. Device data will be reviewed by study physicians initially weekly then monthly to adjust settings as needed to optimize treatment. Follow-up visits will be conducted at 1, 3, 6, and 12 months at the clinic and will include clinical assessment, venous blood gas, questionnaire administration, device adherence review, and adverse event monitoring. Feasibility outcomes including recruitment rate, protocol completion, and treatment adherence will be reported