The ECMO-Free Trial

NCT ID: NCT05486559

Last Updated: 2026-02-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

NA

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-07

Study Completion Date

2027-07-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Extracorporeal Membrane Oxygenation Complication

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Open-label, parallel-group, randomized controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

ECMO-free protocol

Intervention Type OTHER

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).

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.

Group Type ACTIVE_COMPARATOR

Usual Care

Intervention Type OTHER

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.

Interventions

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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).

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Whitney Gannon

Acute Care Nurse Practitioner

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jonathan D Casey, MD, MSc

Role: STUDY_DIRECTOR

Vanderbilt University Medical Center

Locations

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UC San Diego Health

San Diego, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Texas Tech University Health Sciences Center of El Paso

El Paso, Texas, United States

Site Status

University of Utah Health

Salt Lake City, Utah, United States

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Al-Fares AA, Ferguson ND, Ma J, Cypel M, Keshavjee S, Fan E, Del Sorbo L. Achieving Safe Liberation During Weaning From VV-ECMO in Patients With Severe ARDS: The Role of Tidal Volume and Inspiratory Effort. Chest. 2021 Nov;160(5):1704-1713. doi: 10.1016/j.chest.2021.05.068. Epub 2021 Jun 21.

Reference Type BACKGROUND
PMID: 34166645 (View on PubMed)

Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1351-63. doi: 10.1016/S0140-6736(09)61069-2. Epub 2009 Sep 15.

Reference Type BACKGROUND
PMID: 19762075 (View on PubMed)

Brodie D, Slutsky AS, Combes A. Extracorporeal Life Support for Adults With Respiratory Failure and Related Indications: A Review. JAMA. 2019 Aug 13;322(6):557-568. doi: 10.1001/jama.2019.9302.

Reference Type BACKGROUND
PMID: 31408142 (View on PubMed)

Broman LM, Malfertheiner MV, Montisci A, Pappalardo F. Weaning from veno-venous extracorporeal membrane oxygenation: how I do it. J Thorac Dis. 2018 Mar;10(Suppl 5):S692-S697. doi: 10.21037/jtd.2017.09.95.

Reference Type BACKGROUND
PMID: 29732188 (View on PubMed)

Vasques F, Romitti F, Gattinoni L, Camporota L. How I wean patients from veno-venous extra-corporeal membrane oxygenation. Crit Care. 2019 Sep 18;23(1):316. doi: 10.1186/s13054-019-2592-5. No abstract available.

Reference Type BACKGROUND
PMID: 31533848 (View on PubMed)

Grant AA, Hart VJ, Lineen EB, Badiye A, Byers PM, Patel A, Vianna R, Koerner MM, El Banayosy A, Loebe M, Ghodsizad A. A Weaning Protocol for Venovenous Extracorporeal Membrane Oxygenation With a Review of the Literature. Artif Organs. 2018 Jun;42(6):605-610. doi: 10.1111/aor.13087. Epub 2018 Jan 18.

Reference Type BACKGROUND
PMID: 29344952 (View on PubMed)

Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7. doi: 10.1056/NEJM200005183422002.

Reference Type BACKGROUND
PMID: 10816184 (View on PubMed)

Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999 Dec;27(12):2609-15. doi: 10.1097/00003246-199912000-00001.

Reference Type BACKGROUND
PMID: 10628598 (View on PubMed)

Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34. doi: 10.1016/S0140-6736(08)60105-1.

Reference Type BACKGROUND
PMID: 18191684 (View on PubMed)

Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996 Dec 19;335(25):1864-9. doi: 10.1056/NEJM199612193352502.

Reference Type BACKGROUND
PMID: 8948561 (View on PubMed)

Ely EW, Meade MO, Haponik EF, Kollef MH, Cook DJ, Guyatt GH, Stoller JK. Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines. Chest. 2001 Dec;120(6 Suppl):454S-63S. doi: 10.1378/chest.120.6_suppl.454s.

Reference Type BACKGROUND
PMID: 11742965 (View on PubMed)

Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto A, Lemaire F. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med. 1994 Oct;150(4):896-903. doi: 10.1164/ajrccm.150.4.7921460.

Reference Type BACKGROUND
PMID: 7921460 (View on PubMed)

Esteban A, Frutos F, Tobin MJ, Alia I, Solsona JF, Valverdu I, Fernandez R, de la Cal MA, Benito S, Tomas R, et al. A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med. 1995 Feb 9;332(6):345-50. doi: 10.1056/NEJM199502093320601.

Reference Type BACKGROUND
PMID: 7823995 (View on PubMed)

Gannon WD, Stokes JW, Bloom S, Sherrill W, Bacchetta M, Rice TW, Semler MW, Casey JD. Safety and Feasibility of a Protocolized Daily Assessment of Readiness for Liberation From Venovenous Extracorporeal Membrane Oxygenation. Chest. 2021 Nov;160(5):1693-1703. doi: 10.1016/j.chest.2021.05.066. Epub 2021 Jun 21.

Reference Type BACKGROUND
PMID: 34166644 (View on PubMed)

Gannon WD, Teijeiro-Paradis R, Prekker ME, Vogelsong MA, Schwartz GS, Odish MF, Nickel NP, Bloom SL, Hansen SJ, Fielding-Singh V, Blough B, Owens RL, Valles R, Adkisson WS, Alvis BD, Bacchetta M, Ford DJ, Gaudio SC, Jelly CA, Landsperger JS, Lingle K, Noblit CC, Rice TW, Del Sorbo L, Stokes JW, Stollings JL, Van Winkle G, Wang L, Imhoff B, Shotwell MS, Fan E, Semler MW, Casey JD; ECMO-Free Investigators and the Pragmatic Critical Care Research Group. Protocol and Statistical Analysis Plan for the ECMO-Free Trial: A Multicenter Randomized Controlled Trial. medRxiv [Preprint]. 2025 Dec 2:2025.12.01.25341410. doi: 10.64898/2025.12.01.25341410.

Reference Type DERIVED
PMID: 41404271 (View on PubMed)

Other Identifiers

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220733

Identifier Type: -

Identifier Source: org_study_id

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