Clinical trial NCT05486559: The ECMO-Free Trial
Official title: ECMO-Free Trial: A Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Extracorporeal Membrane Oxygenation Complication
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2022-08-03
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, parallel-group, randomized controlled trial
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to successful discontinuation of ECMO
timeFrame: From randomization to time of hospital discharge or until day 60.
Secondary outcomes:
measure: ECMO-free days to day 60
timeFrame: From randomization to death or hospital discharge through day 60.
Other outcomes:
measure: Unsafe discontinuation of ECMO
timeFrame: From randomization to 48 hours after decannulation.
measure: Recannulation within 30 days of decannulation
timeFrame: From decannulation until 30 days after decannulation.
measure: Survival to decannulation
timeFrame: From randomization to until the date of death or the date of decannulation, whichever came first, through day 60.
measure: Respiratory support-free days to day 60
timeFrame: From randomization to the date of death or discharge, whichever came first, through day 60.
measure: ICU-free days to day 60
timeFrame: From randomization to the date of death or discharge, whichever came first, through day 60.
measure: Ventilator-free days to day 60
timeFrame: From randomization to the date of death or discharge, whichever came first, through day 60.
measure: Hospital-free days to day 60
timeFrame: From randomization to the date of death or discharge, whichever came first, through day 60.
measure: 60-day in-hospital mortality
timeFrame: From randomization to the date of death or discharge, whichever came first, through day 60.
Locations:
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Vanderbilt University Medical Center
name: Jonathan D Casey, MD, MSc
role: STUDY_DIRECTOR
References:
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