The ECMO-Free Trial

NCT05486559 | Active Not Recruiting DMC

• 1 other identifier: 220733
• Study Type: interventional
• Target: 225
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Extracorporeal Membrane Oxygenation Complication

Outcome Measures

Primary Outcomes (1)

• Time to successful discontinuation of ECMO

  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 Outcomes (1)

• ECMO-free days to day 60

  From randomization to death or hospital discharge through day 60.

Other Outcomes (8)

• Unsafe discontinuation of ECMO

  From randomization to 48 hours after decannulation.

• Recannulation within 30 days of decannulation

  From decannulation until 30 days after decannulation.

• Survival to decannulation

  From randomization to until the date of death or the date of decannulation, whichever came first, through day 60.

Study Arms (2)

The ECMO-free Protocol group

EXPERIMENTAL

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

The Usual Care Group

ACTIVE COMPARATOR

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

Interventions

ECMO-free protocol 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 ECMO-free Protocol group

Usual Care 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.

The Usual Care Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (8)

UC San Diego Health

San Diego, California, 92037, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Texas Tech University Health Sciences Center of El Paso

El Paso, Texas, 79905, United States

Location

University of Utah Health

Salt Lake City, Utah, 84112, United States

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (15)

• 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.

  PMID: 34166645 BACKGROUND

• 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.

  PMID: 19762075 BACKGROUND

• 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.

  PMID: 31408142 BACKGROUND

• 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.

  PMID: 29732188 BACKGROUND

• 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.

  PMID: 31533848 BACKGROUND

• 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.

  PMID: 29344952 BACKGROUND

• 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.

  PMID: 10816184 BACKGROUND

• 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.

  PMID: 10628598 BACKGROUND

• 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.

  PMID: 18191684 BACKGROUND

• 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.

  PMID: 8948561 BACKGROUND

• 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.

  PMID: 11742965 BACKGROUND

• 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.

  PMID: 7921460 BACKGROUND

• 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.

  PMID: 7823995 BACKGROUND

• 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.

  PMID: 34166644 BACKGROUND

• 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.

  PMID: 41404271 DERIVED

Study Officials

• Jonathan D Casey, MD, MSc

  Vanderbilt University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Acute Care Nurse Practitioner

Model Details: Open-label, parallel-group, randomized controlled trial

Study Record Dates

• First Submitted: August 1, 2022
• First Posted: August 3, 2022
• Study Start: September 7, 2022
• Primary Completion: April 18, 2026
• Study Completion (Estimated): May 18, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

CA (1); US (7)