Routine vs On-demand ECMO for Lung Transplantation (REVOLUTION)

RoutinE Versus On-demand Intraoperative Extracorporeal Membrane Oxygenation (ECMO) During LUng TransplantatION (REVOLUTION)

Lung transplantation is a complex procedure performed in patients with terminal lung disease. The transplant procedure stresses the patient's heart and lungs, which are already taxed by the underlying disease process. The heart-lung machine is occasionally used to support the patient and ensure adequate oxygen supply to other organs during the operation. It can be used routinely in all patients or selectively in patients who exhibit reduced oxygen supply to the remaining organs. This process, known as cardiopulmonary bypass (CPB), pumps blood out of the body to a heart-lung machine that removes carbon dioxide and returns oxygen-filled blood to the body.

Although using the CPB increases the risk of bleeding, infection, and coagulation complications, it should still be considered in high-risk patients to compensate for more severe complications such as kidney failure and stroke caused by a lack of cardiopulmonary support. Extracorporeal membrane oxygenation (ECMO) is a recently developed CPB variation associated with fewer bleeding complications. It has recently replaced the traditional heart-lung machine as the preferred method of cardiopulmonary support during lung transplantation. Since ECMO is associated with fewer complications than standard CPB, many centers have increased their use of ECMO during lung transplantation. Some have even employed it routinely. However, there remains significant debate on how often it should be used.

Therefore, the study's main objective is to compare the two approaches in lung transplantation, i.e., routine use versus selective use, and to determine if one approach is preferable to the other.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Failure; Pulmonary Fibrosis; Interstitial Lung Disease (ILD); COPD (Chronic Obstructive Pulmonary Disease)
• Intervention / Treatment: Device: Routine ECMO; Device: On-demand ECMO

Detailed Description

This study compares two approaches to intraoperative cardiopulmonary support during lung transplantation: routine cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) versus selective use. Despite recent improvements in lung transplant outcomes, postoperative complications are common. Intraoperative hemodynamic management is vital to the success of lung transplantation. Many centers, including all four Canadian centers, use ECMO to provide intraoperative support. However, lung transplantation without cardiopulmonary support may be possible in certain patients. In such patients, the transplant may be started without ECMO. ECMO may be initiated "on-demand" if hemodynamic embarrassment or hypoxia occurs. Conversely, the opposite approach would be routinely conducting all lung transplants using ECMO. The current practice in many centers is to use ECMO selectively. By extension, the investigators believe that more liberal use of intraoperative ECMO will produce less intraoperative hemodynamic instability and hypoxia. However, it is unclear the extent of ECMO use necessary to improve the incidence of postoperative hypoperfusion-related complications. Should ECMO be used routinely in all patients or selectively based on the intraoperative course? The study is a prospective, randomized, controlled trial with two treatment arms: routine support with ECMO versus selective (on-demand) support with ECMO. Study population (Inclusion and exclusion criteria): All patients, 18 years of age or older, undergoing lung transplantation will be screened for participation. We will exclude patients who require intraoperative ECMO, multi-organ transplants, and retransplantation Arms and Interventions: On-demand ECMO: The transplant will be planned without cardiopulmonary support in this group. Intraoperative ECMO will be employed if there is an inability to maintain adequate organ perfusion and oxygen delivery despite resuscitation. Routine ECMO: Routine intraoperative ECMO in all patients, regardless of hemodynamic status. Primary outcome: Intensive care unit (ICU)-free days in the first 28 days post-lung transplant.

• Study Type: Interventional
• Enrollment (Estimated): 218
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Basil Nasir, MD; Phone Number: 24543 514-890-8000; Email: basilsnasir@gmail.com
• Study Contact Backup: Name: Alex Moore, MD; Phone Number: 12171 514-890-8000; Email: alex.moore@umontreal.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2G3
      • Not yet recruiting
      • Univeristy of Alberta & Alberta Health Services
      • Contact: Jason Weatherald, MD, MSc; Phone Number: 780 492 9937; Email: weathera@ualberta.ca
      • Sub-Investigator: Jayan Nagendran, MD PhD
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Not yet recruiting
      • Vancouver General Hospital
      • Contact: Christopher Durkin, MD; Phone Number: 604 875-4111; Email: Christopher.durkin@vch.ca
  • Ontario
    • Toronto, Ontario, Canada, M5G 1M1
      • Not yet recruiting
      • University Health Network / Toronto General Hospiatl
      • Contact: Marcelo Cypel, MD, MSc; Phone Number: 4163404800; Email: marcelo.cypel@uhn.ca
      • Sub-Investigator: Laura Donahoe, MD, MSc
  • Quebec
    • Montreal, Quebec, Canada, H2X3E4
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal
      • Contact: Basil Nasir, MD; Phone Number: 24543 514-890-8000; Email: basilsnasir@gmail.com
      • Contact: Alex Moore, MD; Phone Number: 12171 514-890-8000; Email: alex.moore@umontreal.ca
      • Sub-Investigator: Caroline Landry, CCP, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing lung transplant surgery

Exclusion Criteria:

• Inability to provide consent for the study
• Retransplantation
• Multi-organ transplantation
• Contra-indication to standard heparin anticoagulation (e.g., heparin-induced thrombocytopenia)
• Lung transplant recipients where intraoperative cardiopulmonary support is mandatory:

• Severe pulmonary hypertension (PH):

  1. Systolic pulmonary artery pressure (PAP) ≥ 80 mm Hg on the most recent echocardiography, right heart catheterization, or pulmonary artery catheter measurement
  2. Mean PAP ≥ 55 mm Hg on the most recent echocardiography, right heart catheterization, or pulmonary artery catheter measurement
  3. The ratio of mean pulmonary to systemic artery pressure of > 0.66
• Moderate to severe right ventricular (RV) hypokinesis or dysfunction
• Left ventricular dysfunction: Defined as ejection fraction (LVEF) less than 45% on echocardiography, ventriculography, computed tomography (CT), or magnetic resonance imaging (MRI)
• Patients requiring concomitant cardiac surgery: For example, significant coronary artery disease (CAD) requiring surgical grafting

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Routine ECMO; Routine ECMO during lung tansplant	Device: Routine ECMO; Routine intraoperative venoarterial ECMO during lung transplant
Active Comparator: On-demand ECMO; Selective, indication-based intraoperative cardiopulmonary support.	Device: On-demand ECMO; Selective, indication-based intraoperative cardiopulmonary support. In this group, the transplant will be planned without cardiopulmonary support. intraoperative venoarterial ECMO will be used selectively based on hemodynamic and/or gas exchange abnormalities : Inability to maintain adequate hemodynamics and stable perfusion despite volume resuscitation and vasopressor administration and in the absence of readily correctable cause; Inability to tolerate pulmonary artery clamping; Inadequate gas exchange despite attempts at the optimization of ventilator parameters and treatments related to respiratory mechanics and ventilation/perfusion matching; Inadequate exposure to the surgical field; The transplant team is concerned about the ability to maintain organ perfusion or ventilate with a lung protective strategy, even if the aforementioned criteria are unmet.; Concerns about donor lung quality and a desire to protect the implanted lung from single lung perfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU-free days	Intensive care unit (ICU)-free days in the first 28 days post-lung transplant (28 minus the ICU length of stay)	From the end of surgery up to 28 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and grade of primary graft dysfunction (PGD) at 0, 24, 48, and 72 hours	The definition is based on the criteria for the International Society of Heart and Lung Transplantation (ISHLT) grading system.	From the end of surgery up to 72 hours after surgery
Incidence of all-cause mortality	Death, whatever the cause	From the end of surgery to 90 days after surgery
Incidence of intraoperative blood product transfusion requirements	Number of packed red blood cell units and total blood product units (red blood cells, plasma, platelets, prothrombin complex concentrates) transfused.	Beginning from the surgical incision up to the arrival to the intensive care unit immediately after surgery
Incidence of perioperative blood product transfusion	Number of packed red blood cell units and total blood product units (red blood cells, plasma, platelets, prothrombin complex concentrates) transfused.	From the beginning of surgery up to 72 hours after surgery.
Intensive care unit and hospital length of stay in days	Lenght of stay in the intensive care and in the hospital	Beginning from the arrival to the intensive care unit immediately after surgery
Incidence of re-intubation after surgery	Need to reintubate after extubation after surgery	From the end of surgery until 28 days after surgery
Acute kidney injury (AKI)	The definition of AKI is based on Kidney Disease; improving global outcomes (KDIGO) classification	From the end of surgery up to 28 days after surgery
The composite incidence of death, disabling stroke, grade 2 or 3 PGD at 72 hours, major bleeding, vascular complications, or stage II or III acute kidney injury	Composite outcome of potential complications related to routine and on-demand ECMO	From the end of surgery up to 3, 14, 28 and 90 days.
Average financial costs and sustainability metrics	The average dollar costs and waste in kg per patient related to the use of ECMO, including perfusionist labour and all materials.	From the beginning of surgery until 28 days after surgery
Incidence of postoperative stroke / cerebrovascular accident	Stroke, disabling stroke or non-disabling stroke.; Stroke: Duration of a focal or global neurological deficit ≥ 24 hours; OR < 24 hours if neuroimaging shows a new hemorrhage or infarct; OR the neurological deficit results in death; Disabling stroke: A modified Rankin Score (mRS) of ≥ 2 at three days OR an increase in at least one mRS category from baseline for individuals with a pre-stroke baseline ≥ 1 16,17.; Non-disabling stroke: An mRS score of < 2 at 14 days or one that does not increase in at least one mRS category from an individuals pre-stroke baseline	From the end of surgery up to 28 days after surgery
Incidence of postoperative bleeding complications	The definition of bleeding complication is based on Bleeding Academic Research Consortium (BARC) classification. Bleeding is defined as Major or Minor.	From the end of surgery up to 28 days after surgery
Duration of mechanical ventilation in hours	BiPAP and CPAP are not considered mechanical ventilation. Tracheostomy is not considered mechanical ventilation if a ventilator is not needed.	Beginning from the arrival to the intensive care unit immediately after surgery
Incidence of postoperative tracheostomy	Need for a tracheostomy after surgery in a patient without a previous tracheostomy	From the end of surgery until 28 days after surgery
Incidence of vascular complications	Major or minor vascular complications (see protocol)	From the end of surgery to 28 days after surgery

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Publications and helpful links

General Publications

• Nasir BS, Weatherald J, Ramsay T, Cypel M, Donahoe L, Durkin C, Schisler T, Nagendran J, Liberman M, Landry C, Overbeek C, Moore A, Ferraro P. Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study. J Heart Lung Transplant. 2024 Jun;43(6):1005-1009. doi: 10.1016/j.healun.2024.02.1454. Epub 2024 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2024
• Primary Completion (Estimated): November 5, 2028
• Study Completion (Estimated): January 15, 2029

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 26, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: ECMO; Lung Transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Obstructive; Fibrosis; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: 2024-11391

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No