Clinical trial NCT06615492: Routine vs On-demand ECMO for Lung Transplantation
Official title: RoutinE Versus On-demand Intraoperative Extracorporeal Membrane Oxygenation (ECMO) During LUng TransplantatION (REVOLUTION)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Respiratory Failure
Interstitial Lung Disease (ILD)
Pulmonary Fibrosis
COPD (Chronic Obstructive Pulmonary Disease)
Keywords: ECMO
Lung Transplantation
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
First posted: 2024-09-26
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 \&gt; 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

Primary outcomes:
measure: ICU-free days
timeFrame: From the end of surgery up to 28 days after surgery
Secondary outcomes:
measure: Incidence and grade of primary graft dysfunction (PGD) at 0, 24, 48, and 72 hours
timeFrame: From the end of surgery up to 72 hours after surgery
measure: Incidence of all-cause mortality
timeFrame: From the end of surgery to 90 days after surgery
measure: Incidence of intraoperative blood product transfusion requirements
timeFrame: Beginning from the surgical incision up to the arrival to the intensive care unit immediately after surgery
measure: Incidence of perioperative blood product transfusion
timeFrame: From the beginning of surgery up to 72 hours after surgery.
measure: Intensive care unit and hospital length of stay in days
timeFrame: Beginning from the arrival to the intensive care unit immediately after surgery
measure: Incidence of re-intubation after surgery
timeFrame: From the end of surgery until 28 days after surgery
measure: Acute kidney injury (AKI)
timeFrame: From the end of surgery up to 28 days after surgery
measure: 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
timeFrame: From the end of surgery up to 3, 14, 28 and 90 days.
measure: Average financial costs and sustainability metrics
timeFrame: From the beginning of surgery until 28 days after surgery
measure: Incidence of postoperative stroke / cerebrovascular accident
timeFrame: From the end of surgery up to 28 days after surgery
measure: Incidence of postoperative bleeding complications
timeFrame: From the end of surgery up to 28 days after surgery
measure: Duration of mechanical ventilation in hours
timeFrame: Beginning from the arrival to the intensive care unit immediately after surgery
measure: Incidence of postoperative tracheostomy
timeFrame: From the end of surgery until 28 days after surgery
measure: Incidence of vascular complications
timeFrame: From the end of surgery to 28 days after surgery
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Univeristy of Alberta &amp; Alberta Health Services
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: University Health Network / Toronto General Hospiatl
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l&amp;#39;Université de Montréal
state: Quebec
Study officials:
References:
citation: 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.