UMIN-ICDS Clinical Trial

Public title

Safe Liberation from V-A ECMO with Pump-Controlled Retrograde Trial Off versus Conventional Weaning Strategies (SAFE-ECMOFF Trial): A Phase II Multicenter Randomized Trial

Acronym

SAFE-ECMOFF Trial

Scientific Title

Safe Liberation from V-A ECMO with Pump-Controlled Retrograde Trial Off versus Conventional Weaning Strategies (SAFE-ECMOFF Trial): A Phase II Multicenter Randomized Trial

Scientific Title:Acronym

SAFE-ECMOFF Trial

Region

Japan

Condition

Patients with V-A ECMO

Classification by specialty

Emergency medicine

Intensive care medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The objective of this study is to determine the optimal weaning trial strategy and its evaluation criteria, which remain unresolved for patients with V-A ECMO.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

The primary outcome is safe liberation from V-A ECMO, defined as the absence of predefined adverse events during two consecutive periods: from randomization to prior to the ECMO decannulation procedure, and from the start of the ECMO decannulation procedure up to 24 hours post-decannulation. From randomization to prior to the ECMO decannulation procedure, the predefined adverse events included CPA, unplanned interruption of ECMO support, major hemorrhagic complications, major thromboembolic complications, and the failure to wean from V-A ECMO. From V-A ECMO decannulation procedure to 24 hours post-decannulation, From the start of the ECMO decannulation procedure to 24 hours post-decannulation, the predefined adverse events consist of CPA, the re-introduction or new insertion of a MCS device, the presence of shock, and cardiac failure.

Key secondary outcomes

The secondary outcomes include the following: (1) the incidence of each individual component comprising the primary outcome; (2) respiratory failure, defined as a PaO2/FiO2 ratio < 200, within 24 hours after V-A ECMO decannulation; (3) all-cause mortality at 28 and 90 days after intervention initiation; (4) modified Rankin Scale scores at 28 and 90 days after intervention initiation; (5) hospital-free days until 90 days after intervention initiation; (6) ECMO-free days until 90 days after intervention initiation; (7) MCS-free days until 90 days after intervention initiation; (8) ICU-free days until 90 days after intervention initiation; (9) ventilator-free days until 90 days after intervention initiation; (10) renal replacement therapy (RRT)-free days until 90 days after intervention initiation; (11) the incidence of adverse events from randomization up to 24 hours after liberation from ECMO; (12) changes of vasopressor/inotrope dosages, Impella flow rates, intra-aortic balloon pump (IABP) settings, vital signs, echocardiographic parameters, and Swan-Ganz catheter parameters from randomization to 24 hours post-ECMO liberation. The hospital-free, ICU-free, ECMO-free, MCS-free, ventilator-free, and RRT-free days were defined as the number of days from day 1 to day 90 after intervention initiation when the patient was alive and free from support for at least 24 consecutive hours. If patients die within 90 days or are still supported after 90 days, zero will be assigned.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

In the control group (conventional group), no additional trials are performed as patients have passed the flow weaning trial. After the V-A ECMO flow is returned to 2.0 L/min, V-A ECMO liberation is performed within 2 days.

Interventions/Control_2

In the intervention group (PCRTO group), prior to initiating PCRTO, it is confirmed that either the activated partial thromboplastin time (aPTT) measured within the past 6 hours is within 1.5 to 2.0 times the baseline value, or the activated clotting time (ACT) measured within the past 1 hour is within 180 to 250 seconds, under continuous infusion of unfractionated heparin. If these thresholds are not met, an intravenous bolus of unfractionated heparin is administered with the aim to achieve the target range.
During PCRTO, the ECMO pump speed is reduced in stepwise fashion to achieve ECMO flow of -1.0 to -0.5 L/min and the sweep gas flow is set to 0 L/min. This state is maintained for 0.5 to 1.0 hour. If all standardized criteria are fulfilled, it is defined as a "successful PCRTO trial". Following a successful trial, the V-A ECMO flow is returned to 2.0 L/min, the sweep gas is returned to its baseline settings, and liberation from V-A ECMO is performed within 2 days.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) Those aged equal to or more than 18 years; (2) those with peripheral ECMO; and (3) those who have reached readiness to wean status.

Key exclusion criteria

The exclusion criteria are as follows: (1) planned configuration change to another mechanical circulatory support (MCS) device, such as a left ventricular assist device, upon ECMO weaning; (2) use of hybrid ECMO; (3) ECMO initiation for non-cardiac indications, including acute aortic dissection or aortic aneurysm, hypothermia, primary cerebral disorders, drug intoxication, trauma, suffocation, or drowning; (4) contraindication to unfractionated heparin; (5) known or suspected pregnancy; (6) ECMO discontinuation due to withdrawal of life-sustaining therapy; (7) prior enrolment in this trial; (8) refusal to participate by patients or representatives; and (9) any other condition deemed ineligible by the attending physician.

Target sample size

155

Name of lead principal investigator

1st name	Kazuki
Middle name
Last name	Matsumura

Organization

Keio University School of Medicine

Division name

Department of Emergency and Critical Care Medicine

Zip code

160-8582

Address

35, Shinanomachi, Shinjyuku, Tokyo, Japan

TEL

0333531211

Email

kazuki.matsumura@keio.jp

Name of contact person

1st name	Kazuki
Middle name
Last name	Matsumura

Organization

Keio University School of Medicine

Division name

Department of Emergency and Critical Care Medicine

Zip code

160-8582

Address

35, Shinanomachi, Shinjyuku, Tokyo, Japan

TEL

0332251323

Homepage URL

Email

kazuki.matsumura@keio.jp

Institute

Keio University School of Medicine

Institute

Department

Personal name

Organization

Self funding

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Keio University School of Medicine, Institutional Review Board

Address

35, Shinanomachi, Shinjyuku, Tokyo, Japan

Tel

0333531211

Email

med-rinri-jimu@adst.keio.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2026

Year

07

Month

13

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2026

Year

06

Month

30

Day

Date of IRB

Anticipated trial start date

2026

Year

09

Month

01

Day

Last follow-up date

2033

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2026

Year

07

Month

11

Day

Last modified on

2026

Year

07

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071189