A trial of extracorporeal CO2 removal in COPD stopped at 18 patients, for money

Design

Randomised controlled trial, terminated early by the sponsor for financial reasons (18 of a planned 192 patients)

Population

Adults with acute hypercapnic respiratory failure from a COPD exacerbation requiring invasive ventilation, who failed or were ineligible for extubation within 24 hours

Primary outcome

Composite of death or severe disability at day 60

Effect

0 of 8 vs 3 of 9 (33%); risk difference -33% (95% CI -65% to 6%), p=0.21; ventilation 7.1 vs 24.3 days, mean difference -17.2 days, p=0.043

X-COPD asked a question worth answering: in acute hypercapnic respiratory failure from a COPD exacerbation, can extracorporeal CO2 removal get patients off the ventilator sooner and spare them its complications? Adults who had failed extubation or were ineligible for it within 24 hours of intubation were randomised to the device or to standard ventilation, with death or severe disability at day 60 as the primary composite.

The sponsor terminated the trial for financial reasons after 18 of a planned 192 patients. The primary endpoint occurred in none of 8 device patients and 3 of 9 evaluable controls (33%; risk difference -33%, 95% CI -65% to 6%; p=0.21). Duration of invasive ventilation was shorter with the device: 7.1 days against 24.3, mean difference -17.2 days, p=0.043. Ventilator-associated pneumonia occurred in none against three. One device patient (12.5%) had severe bleeding.

None of that is a result. Eighteen patients across two arms cannot support a conclusion about death or disability, the primary endpoint's confidence interval crosses zero, and the device-free days analysis was post hoc and exploratory. The one severe bleed in eight patients is the number to hold onto, because anticoagulated extracorporeal circuits are how this technology usually fails.

So nothing changes today. The reason to read it is that a promising question has been left unanswered for a reason unrelated to the science, and the next time a patient is stuck on a ventilator after a COPD exacerbation, the honest position is still that we do not know whether this helps.

• Do not adopt extracorporeal CO2 removal for COPD outside a trial on the basis of this
• Weight the bleeding risk: one severe bleed in eight treated patients, with anticoagulation required
• The ventilation-duration difference is the most robust signal, and it is still 18 patients
• Standard care remains early non-invasive ventilation, treated precipitant, and careful weaning
• Note the trial stopped for funding, not futility or harm - the question is open, not answered

The statistics, in plain English

A risk difference of -33% with an interval running from -65% to +6% includes zero, meaning the data are compatible with a large benefit and with a small harm - unavoidable at this sample size. The ventilation-duration p of 0.043 looks convincing but rests on group means of 7.1 and 24.3 days with a standard deviation of 21.4 in the control arm, so one or two prolonged cases are driving it. A post hoc exploratory analysis, like the device-free days here, is a hypothesis, not a finding, because the comparison was chosen after seeing the data.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.