Rationale: It is unclear whether extracorporeal CO₂ removal (ECCO₂R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD).

Objectives: To determine whether ECCO₂R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV.

Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018–2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO₂R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33).

Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0–0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO₂R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00–1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO₂R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73).

Conclusions: In subjects with exacerbation of COPD, the use of ECCO₂R compared with standard care did not improve VFD-5.