Effectiveness of Automatically-adjusted vs. Manually-adjusted Noninvasive Ventilation in Obesity Hypoventilation Syndrome: A Randomized Clinical Trial

Rationale Obesity hypoventilation syndrome (OHS) is treated with non-invasive 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. Objective 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-EPAP) or manually-adjusted NIV (bilevel PAP ST mode). Measurements The primary outcome was change in daytime PaCO2 at 12 months, with the non-inferiority premise set at -2 mmHg. 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] mmHg in the auto-adjusted group and -8.7 [-9.1;-8.3] mmHg in the manually-adjusted group, with mean adjusted difference of 0.15 mmHg between groups ([low confidence limit -1.4]; non-inferiority P = 0.01). Cost-effectiveness was favorable to auto-adjusted group with a saving of 15287€(95% CI: -2370; -6854) 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.