Extracorporeal CO₂ elimination for acute exacerbation of severe COPD requiring invasive mechanical ventilation: a randomized controlled trial (the X-COPD trial).

Abstract

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