The ECMO-Free Trial

May 1, 2026 updated by: Whitney Gannon, Vanderbilt University Medical Center

ECMO-Free Trial: A Multicenter Randomized Controlled Trial

Decannulation from venovenous extracorporeal membrane oxygenation (VV-ECMO) at the earliest and safest time would be expected to improve outcomes and reduce cost. Daily assessments for readiness to liberate from therapies have demonstrated success in other realms of critical care. A recent single-center study demonstrated that a protocolized daily assessment of readiness for liberation from VV-ECMO was feasible and did not raise any major safety concerns, but the effect of this protocolized daily assessment on clinical outcomes remains unclear. Further, the manner in which ECMO is provided, weaned, and discontinued varies significantly between centers, raising persistent concerns regarding widespread adoption of protocolized daily assessment of readiness for liberation from VV-ECMO. Data from large a randomized controlled trial is needed to compare the effects of a protocolized daily assessment of readiness for liberation from VV-ECMO versus usual care on duration of ECMO support and other clinical outcomes.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Complication rates, economic consequences, and resource limitations associated with the use of venovenous ECMO (VV-ECMO) are widely recognized. Decannulation at the earliest and safest possible time would be expected to improve clinical outcomes, reduce cost, and optimize resource allocation. Yet, there are no data comparing weaning strategies for decannulation from VV-ECMO, and there is significant variation between centers in approaches to weaning VV-ECMO.

Current approaches to weaning VV-ECMO generally rely on clinicians to identify signs of lung recovery and initiate incremental reductions in blood flow rate, fraction of delivered oxygen (FdO2), and sweep gas flow rate4-6. This approach has been previously outlined in guidelines distributed by the Extracorporeal Life Support Organization, expert opinion, and in small descriptive studies, though little data exist to support this strategy. Further, these approaches run counter to the large body of literature for assessing readiness for "liberation" from sedation and mechanical ventilation in which incremental reductions (weaning) have repeatedly been shown to be inferior to protocolized daily assessments (spontaneous awakening trials and spontaneous breathing trials7-11).

Prior data suggest that clinicians underestimate readiness for liberation from organ support and suggest that protocols to identify readiness for liberation are superior to clinician judgement9,11. Compared to incremental weaning, spontaneous awakening trials and spontaneous breathing trials have been shown to dramatically shorten the duration of support, reduce intensive care costs, and improve outcomes7-13. Until recently, this approach to liberating patients from a therapy had not been applied to ECMO. Our groups recently conducted a 26-patient, prospective, single-arm, safety and feasibility study to develop and refine a protocol for daily assessment of readiness to liberate from VV-ECMO at a single center14. The results of this study, published in CHEST, suggested that a protocolized daily assessment of readiness for liberation from VV-ECMO is feasible and safe. Further, the median time from first passed trial to decannulation was 2 days, suggesting that a daily protocolized assessment might identify candidates for decannulation earlier than occurs in usual care. However, as a single-arm feasibility study, the prior study was insufficient to determine whether dedicating resources to a protocolized daily assessment of readiness to liberate from VV-ECMO affects patient outcomes. Further, the manner in which ECMO is provided, weaned, and discontinued varies significantly between centers, raising persistent concerns regarding the feasibility of widespread adoption of protocolized daily assessment of readiness for liberation from VV-ECMO.

Additional data from a large, multi-center randomized controlled trial are needed to compare the effects of a protocolized daily assessment of readiness for liberation from VV-ECMO versus usual care on duration of ECMO support, measures of unsafe liberation, and other clinical outcomes.

Primary aim: Compare the effects of a protocolized daily assessment of readiness for liberation from VV-ECMO (ECMO-free protocol) versus liberation strategy directed by the clinical team (usual care) on time to successful decannulation via a large multi-site randomized controlled trial.

Secondary aim: To compare the effect of a once daily protocolized assessment of readiness to liberate from ECMO (ECMO-free protocol) versus a liberation strategy directed by the clinical team (usual care) on the number of days alive and free of ECMO by day 60 (ECMO-free days).

To address these aims, we propose a multi-center, open-label, parallel-group, randomized controlled trial comparing a protocolized daily assessment of readiness for liberation from VV-ECMO (ECMO-free protocol) to usual care. All patients who receive VV-ECMO in a participating unit of an adult hospital and meet all inclusion criteria and no exclusion criteria will be eligible for participation. Eligible participants or surrogate decision makers will be approached for consent. Following documentation of written informed consent, patients will be enrolled and randomly assigned to receive the ECMO-free protocol or usual care. The study will control VV-ECMO weaning strategy until the first of decannulation or death. All other decisions regarding critical care support, interventional therapies, and medical treatment will remain at the discretion of the treating physician and consulting teams.

Study Type

Interventional

Enrollment (Estimated)

225

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Toronto General Hospital
  • United States
    • California
      • San Diego, California, United States, 92037
        • UC San Diego Health
      • Stanford, California, United States, 94305
        • Stanford University
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center
      • El Paso, Texas, United States, 79905
        • Texas Tech University Health Sciences Center of El Paso
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient receiving VV-ECMO
  • Patient is located in a participating unit of an adult hospital

Exclusion Criteria:

  • Patient is pregnant
  • Patient is a prisoner
  • Patient is < 18 years old
  • Participant is receiving ECMO as bridge to transplant
  • Participant is receiving a hybrid configuration that includes an arterial cannula
  • Patient has received VV-ECMO for > 48 hours

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: The ECMO-free Protocol group
For patients assigned to the ECMO-free protocol group, the study personnel will perform the ECMO-free protocol daily from enrollment until the first of death or ECMO decannulation; results will be recorded and shared with the treatment team. Final decisions regarding decannulation will be made by treating clinicians who are aware of the results of daily ECMO-free protocolized assessments.
Other: ECMO-free protocol

All patients randomized to the ECMO-Free Protocol Group will receive a protocolized daily assessment of readiness for liberation from VV-ECMO, which will be initiated between 6:00 AM local time and 10:00 AM local time. If the patient is enrolled after 10:00 AM local time the ECMO-free protocol will begin the following calendar day.

The ECMO-Free Protocol is a 3-step process of assessing readiness for liberation from VV-ECMO: a safety screen (Phase 1: ECMO-Free Safety Screen), titration of the non-ECMO fraction of inspired oxygen (Phase 2: Non-ECMO respiratory support titration), and a trial of cessation of sweep gas flow (Phase 3: ECMO-Free Trial).
Active Comparator: The Usual Care Group
For patients assigned to the usual care group, ECMO weaning and assessments of readiness for ECMO decannulation will be at the discretion of treating clinicians.
Other: Usual Care
All patients randomized to the Usual Care Group will undergo assessments of readiness for liberation, weaning, and decannulation at the discretion of the treatment team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to successful discontinuation of ECMO
Time Frame: From randomization to time of hospital discharge or until day 60.
The primary outcome will be the time (in days) from randomization (time zero) until the time of the final successful discontinuation of ECMO. Discontinuation of ECMO will be considered to be successful if a patient undergoes decannulation and survives without ECMO until day 60. For patients who are decannulated and subsequently experience recannulation, the time of successful discontinuation of ECMO will be based on the final decannulation. Data collection will cease at the time of hospital discharge or day 60.
From randomization to time of hospital discharge or until day 60.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ECMO-free days to day 60
Time Frame: From randomization to death or hospital discharge through day 60.
The number of days alive and free of ECMO to day 60 (ECMO-free days) will be calculated as 60 minus the number of calendar days from randomization to final decannulation. Patients receiving ECMO at day 60 will receive a value of "0". Patients who die before day 60 or hospital discharge will receive a value of "0".
From randomization to death or hospital discharge through day 60.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Unsafe discontinuation of ECMO
Time Frame: From randomization to 48 hours after decannulation.
Unsafe liberation will be defined according to a previously published definition.1 A patient will be classified as having experienced unsafe discontinuation of ECMO if he or she experiences any of the following within 48 hours of decannulation: VV-ECMO recannulation, sustained (> 4 hours) escalation of mechanical ventilation (change from a partially assisted mode to controlled MV, or dynamic driving pressure greater than or equal to 16 and delta change from previous setting of greater than or equal to 5 cm H2O, or increase in FiO2 to > 80%), use of rescue therapies (i.e. new need for paralysis and deep sedation, or inhaled pulmonary vasodilators, or high frequency oscillatory ventilation, or new worsening hemodynamics requiring addition of any vasoactive agents with no evidence of sepsis or hypovolemia).
From randomization to 48 hours after decannulation.
Recannulation within 30 days of decannulation
Time Frame: From decannulation until 30 days after decannulation.
Reinstituting ECMO support within 30 days of discontinuation.
From decannulation until 30 days after decannulation.
Survival to decannulation
Time Frame: From randomization to until the date of death or the date of decannulation, whichever came first, through day 60.
Alive at time of decannulation
From randomization to until the date of death or the date of decannulation, whichever came first, through day 60.
Respiratory support-free days to day 60
Time Frame: From randomization to the date of death or discharge, whichever came first, through day 60.
Number of days free of respiratory support between randomization and day 60.
From randomization to the date of death or discharge, whichever came first, through day 60.
ICU-free days to day 60
Time Frame: From randomization to the date of death or discharge, whichever came first, through day 60.
Number of days alive and not in the ICU between randomization and day 60.
From randomization to the date of death or discharge, whichever came first, through day 60.
Ventilator-free days to day 60
Time Frame: From randomization to the date of death or discharge, whichever came first, through day 60.
Number of days alive and free from mechanical ventilation between randomization and day 60.
From randomization to the date of death or discharge, whichever came first, through day 60.
Hospital-free days to day 60
Time Frame: From randomization to the date of death or discharge, whichever came first, through day 60.
Number of days alive and not in the hospital between randomization and day 60.
From randomization to the date of death or discharge, whichever came first, through day 60.
60-day in-hospital mortality
Time Frame: From randomization to the date of death or discharge, whichever came first, through day 60.
Death prior to hospital discharge.
From randomization to the date of death or discharge, whichever came first, through day 60.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Investigators

  • Study Director: Jonathan D Casey, MD, MSc, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 7, 2022

Primary Completion (Actual)

April 18, 2026

Study Completion (Estimated)

May 18, 2026

Study Registration Dates

First Submitted

August 1, 2022

First Submitted That Met QC Criteria

August 1, 2022

First Posted (Actual)

August 3, 2022

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • 220733

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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