Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) requiring invasive mechanical ventilation (IMV) are associated with high mortality and long-term disability. Extracorporeal CO₂ removal (ECCO₂R) using modern high-capacity devices may facilitate early endotracheal extubation and reduce IMV-related complications.

Objectives: To evaluate whether ECCO2R-facilitated early extubation improves clinical outcomes compared with standard IMV in patients with severe AE-COPD requiring IMV.

Methods:  Adults with acute hypercapnic respiratory failure due to AE-COPD requiring IMV who failed or were ineligible for extubation within 24 hours of intubation were randomized to ECCO2R or no ECCO2R. The primary endpoint was a composite of death or severe disability at day 60.

Results: 18 patients were randomized before the trial was terminated early by the sponsor for financial reasons (planned enrollment: 192). The primary composite endpoint occurred in 0/8 ECCO2R-treated patients versus 3/9 evaluable IMV-treated patients (33%; risk difference −33%; 95% CI −65% to 6%; p = 0.21). IMV duration was shorter in the ECCO2R group (7.1 ± 2.0 vs. 24.3 ± 21.4 days; median 7.0 vs. 16.0 days; mean difference −17.2 days; p = 0.043), yielding, in a post hoc exploratory analysis, more overall device-free days at day 29 (17 ± 4 device-support-free day compared with 8 ± 7 days in the IMV group (p = 0.011)). Ventilator-associated pneumonia occurred in 0 versus 3 patients (37.5%), respectively. Sedation was discontinued earlier in the ECCO₂R group. Severe bleeding occurred in one ECCO₂R-treated patient (12.5%).

Conclusions: In this prematurely terminated trial, ECCO₂R-facilitated early extubation using a device with a capacity to eliminate more than 50% of the average CO2 production, was associated with a shorter duration of invasive mechanical ventilation. Numerical trends favored ECCO2R across several secondary outcomes, although interpretation is limited by premature termination and the very small sample size. Adequately powered multicenter trials are warranted.