Routine Versus Selective Intraoperative ECMO in Lung Transplant

Randomized Trial of Routine Versus Selective Use of Intraoperative Extracorporeal Mechanical Support During Lung Transplantation : a Pilot Study

Intraoperative hemodynamic management is vital in the success of lung transplantation. Significant intraoperative hemodynamic compromise and hypoxic episodes may contribute to an increase in severe postoperative complications related to hypoperfusion, including cerebrovascular accidents, acute kidney injury, and mesenteric ischemia. In certain lung transplant recipients, intraoperative cardiopulmonary support is mandatory because certain factors would make "off-pump" transplants unsafe. These include severe pulmonary hypertension or severe ventricular dysfunction. In such patients, routine intraoperative support should be employed. However, it is possible to conduct the lung transplant without cardiopulmonary support in the remainder of patients who do not have severe pulmonary hypertension or right heart dysfunction. In such patients, the lung transplant may be started without cardiopulmonary support. However, cardiopulmonary support may be initiated "on-demand" if there is development or impending hemodynamic embarrassment or hypoxia. Conversely, the opposite approach would be to routinely conduct all lung transplant operations using cardiopulmonary support, which may also lead to specific ECMO-related complications.

The investigators question whether on demand intraoperative ECMO in patients with significant risk factors will produce severe postoperative complications in a rate similar to routine ECMO.

Study Overview

• Status: Active, not recruiting
• Conditions: Postoperative Complications; Lung Transplant; Complications; Extracorporeal Circulation; Complications
• Intervention / Treatment: Device: On demand ECMO; Device: Routine ECMO

Detailed Description

Hypothesis: In patients where cardiopulmonary bypass (CPB) / ECMO is not mandatory, on-demand use of intra-operative ECMO is equivalent to routine use for patients undergoing lung transplant.

The study will be a prospective, randomized controlled trial. The investigators seek to compare outcomes of two different strategies of cardiopulmonary support during lung transplantation; routine support with ECMO versus selective (on-demand), indication- based support with ECMO. The allocation ratio will be 1:1. A multi-center trial is necessary to allow for a sufficient sample size. However, the investigators believe a pilot study is essential to determine feasibility before embarking on such a significant undertaking.

In this preliminary pilot study, recruitment will be limited to lung transplant patients at the Centre hospitalier de l'Universite de Montreal (CHUM). The primary purpose of the pilot study will be to define recruitment ability and assess the feasibility of conducting the study. Depending on the results of this pilot study, the next step would be to expand the study to multiple lung transplant centers to achieve an adequate sample size and power, allowing the investigators to answer the question of interest.

• Study Type: Interventional
• Enrollment (Anticipated): 29
• 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
  • Quebec
    • Montreal, Quebec, Canada, H2X3E4
      • Centre Hospitalier de l'Universite de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients undergoing lung transplant surgery during the study period (6 months)

Exclusion Criteria:

1. Inability to provide consent for the study or patient refusal
2. Retransplantation
3. Multi-organ transplantation

4. Lung transplant recipients where intraoperative support is mandatory and "off- pump" transplant would be unsafe:

   a. Severe pulmonary hypertension (PH):

   i. Systolic pulmonary artery pressure (PAP) ≥ 80 mm Hg on echocardiography, right heart catheterization, or pulmonary artery catheter measurement

   ii. Mean PAP ≥ 55 mm Hg on echocardiography, right heart catheterization, or pulmonary artery catheter measurement

   iii. The ratio of mean pulmonary to systemic artery pressure of more than 0.66

   b. Moderate to severe right ventricular (RV) hypokinesis or dysfunction

   c. Left ventricular dysfunction: Defined as ejection fraction (LVEF) < 50% on echocardiography, ventriculography, computed tomography (CT), or magnetic resonance imaging (MRI)

   d. Significant coronary artery disease (CAD)requiring stenting or surgical grafting

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: On demand ECMO (study group)	Device: On demand ECMO; Selective, indication-based intraoperative cardiopulmonary support. In this group, the transplant will be planned without cardiopulmonary support. intraoperative ECMO will be used selectively based on hemodynamic and/or gas exchange abnormalities : Inability to maintain adequate hemodynamics and stable perfusion or oxygenation during surgery; Prolonged high dose pressor required to maintain adequate perfusion; A sustained drop in cerebral saturation > 25% of baseline despite initial attempts at optimization; 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
Active Comparator: Routine ECMO (control group)	Device: Routine ECMO; Routine ECMO during lung tansplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Study recruitment rate	6 months after the onset of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients loss to follow-up	1 year
The composite incidence of death, disabling stroke, grade 2 or 3 primary graft dysfunction at 72 hours, major bleeding (BARC grade 3a, 3b or 5), vascular complications, or stage II or III acute kidney injury at 14 days.	14 days
Incidence of all-cause mortality at 30 days, 90 days, and one year	1 year
Incidence of postoperative stroke / cerebrovascular accident	14 days
Incidence of an Early major postoperative neurologic complication (EMPNC): This includes stroke, severe encephalopathy, and severe seizures diagnosed within 14 days after surgery.	14 days
Incidence of severe postoperative complications. This is defined as Clavien-Dindo grade III complication or greater	14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and grade of primary graft dysfunction (PGD) at 0, 24, 48, and 72 hours		From the end of surgery up to 72 hours after surgery
Incidence of postoperative bleeding complications. The definition of bleeding complication is based on Bleeding Academic Research Consortium (BARC) classification		14 days after surgery
Intraoperative blood product transfusion requirements		From the beginning of surgery to transfer to the intensive care unit
Perioperative blood product transfusion requirements	From the beginning of surgery to 14 days after surgery, including return to the operating room for subsequent surgeries	14 days
Intensive care unit and hospital length of stay in days		Beginning from the arrival to the intensive care unit immediately 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, up to about 30 days
Incidence of re-intubation		14 days
Incidence of postoperative tracheostomy		21 days
Incidence of acute kidney injury (AKI) within 14 days. The definition of AKI is based on Kidney Disease; improving global outcomes (KDIGO) classification		14 days
Incidence of vascular complications		14 days
Forced expiratory volume at 1 second (FEV1) at 1 year		1 year
Incidence of stroke		1 year
Incidence of acute rejection episodes		1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Actual): March 15, 2023
• Study Completion (Anticipated): March 15, 2024

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: 2023-10663

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