EOLIA Trial

NEJM

May 24, 2018

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

What was the research question?

  • Is early initiation of Extracorporeal Membrane Oxygenation (ECMO) in patients with severe ARDS, associated with reduction of 60-day mortality compared to standard care?


How did they do it?

  • A prospective, multicenter, randomized, controlled trial, with a 1:1 ratio assignment 64 centers predominantly in France

  • Only research staff members were blinded but not participants or clinical staff.

  • Calculated sample size of 331 patients for 80% power to detect 20% difference in mortality and an alpha level of 5%.

  • Included ARDS patients who were mechanically ventilated for less than 7 days with PaO2:FIO2 ratio <50 mmHg for >3 hours; or PaO2:FIO2 <80 mmHg for >6 hours; or arterial blood pH <7.25 with a partial pressure of arterial carbon dioxide (PaCO2) >60 mmHg for >6 hours.

  • Patients were randomized to receive Venovenous ECMO and low-level mechanical ventilation (124 patients) or protective lung strategy and adjuvant therapies (neuromuscular blockade, proning, recruitment maneuvers, and bicarbonate) as needed (125 patients).

  • Cross over for SaO2 <80% for over 6 hours.

  • Primary outcome was 60-day mortality and secondary end point was treatment failure (defined as a crossover to ECMO or death in patients in the control group and as death in patients in the ECMO group).

  • The data safety monitoring board recommended stopping the trial at the 4th interim analysis (249 out of331) for futility.


What did they find?

  • 60-day mortality (primary outcome) was not statistically different in ECMO compared to control (35% vs. 46% p=0.09).

  • Treatment failure was lower in the ECMO group compared to control group (35% vs. 58%, p<0.001).

  • A relatively high cross over to ECMO occurred in 28% of control patients with higher mortality (57% compared to 40% in the remaining patients in the control group).

  • More patients in the ECMO group with severe thrombocytopenia (27% vs. 16%; ARR 11 %; 95% CI, 0 to 21), bleeding events (46% vs. 28%; ARR 18%; 95% CI, 6 to 30) and less ischemic stroke (no patients vs. 5%; ARR -5%; 95% CI, −10 to −2).


Any limitations?

  • Unblinded and Underpowered to detect difference as it was stopped early.

  • Presumed mortality in the control group of 60% was higher than the actual mortality and a difference of 20% reduction in ARR was overestimated. This affected the sample size and the power of the study. High risk for false negative results.

  • A high cross over rate reduced the effectiveness of ECMO treatment (those patients were started ECMO at later time and they are much sicker patients).

  • A high possibility of clinician equipoise as the cross over decision was at the discretion of unblinded treating clinicians.

  • Possible selection bias, as the majority of ARDS patients were male and had pneumonia and septic shock.


What does it mean?

  • Early initiation of ECMO did not improve 60-day mortality in severe ARDS patients compared to a strategy of conventional mechanical ventilation and ECMO as a rescue therapy.

  • However, the study does not provide conclusive support for the benefit of ECMO in severe ARDS as secondary outcome of treatment benefit is higher in the ECMO group.

EOLIA Trial