Rationale: Obesity hypoventilation syndrome (OHS) is treated with noninvasive ventilation (NIV) that is titrated during polysomnography. Auto-adjusted NIV could obviate the need for polysomnographic titration, thereby reducing costs and delays in care. However, non-inferiority long-term clinical trials comparing auto-adjusted NIV with manually-adjusted NIV are lacking.
Objectives: To determine the comparative effectiveness of automatic vs manual NIV modality in OHS.
Methods: In this multicenter, blinded, parallel group, non-inferiority and cost-effectiveness trial, we randomly assigned treatment-naïve ambulatory patients with OHS to auto-adjusted NIV (volume-targeted pressure support with auto-expiratory positive airway pressure) or manually-adjusted NIV (bilevel Positive Airway Pressure Spontaneous Timed mode (PAP ST).
Measurements: The primary outcome was change in daytime PaCO2 at 12 months, with the non-inferiority premise set at -2 mm Hg. Secondary outcomes included symptoms, quality of life, and healthcare resource utilization. Intention-to-treat and per-protocol analyses were performed.
Main results: 205 ambulatory patients with OHS were randomized, 107 to auto-adjusted NIV and 89 to manually-adjusted NIV. The mean [95% CI] improvement in PaCO2 was -9.2 [-9.7; -8.7] mm Hg in the auto-adjusted group and -8.7 [-9.1; -8.3] mm Hg in the manually-adjusted group, with mean adjusted difference of 0.15 mm Hg between groups ([low confidence limit -1.4]; non-inferiority P = .01). Cost-effectiveness was favorable to auto-adjusted group with a saving of 1528 € (95% CI, -2 370; -6 854) per patient. There were no significant differences in other secondary outcomes.
Conclusions: In ambulatory patients with OHS, auto-adjusted NIV had a non-inferior long-term effectiveness compared to manually-adjusted NIV while being more cost-effective. Auto-adjusted NIV may be preferred in clinical practice given its lower complexity and cost.
Clinicaltrial.gov identifier: NCT04327336.
Keywords: auto-adjusted noninvasive ventilation; noninvasive ventilation; obesity hypoventilation syndrome; sleep apnea.
© The Author(s) 2026. Published by Oxford University Press on behalf of the American Thoracic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.