A Study of Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation

Study Overview
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Brief Summary
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The purpose of this research study is to compare the technique of performing bilateral lung transplantation off-pump vs venoarterial ECMO (VA ECMO). The goal of the trial is to determine which technique has lower rates of primary graft dysfunction.

Detailed Description
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The Investigators of the Extracorporeal Life Support Registry in Lung Transplantation (ECLS Registry) has studied the impact of the type of intraoperative extracorporeal life support on primary graft dysfunction (PGD) after lung transplantation (LTx) in an international registry. The investigators have demonstrated that severe PGD at 48-72 hours is greater when LTx is performed using cardiopulmonary bypass (CPB) (43%) when compared to veno-arterial (VA) ECMO. However, PGD after VA ECMO remained high (29%) when compared to off-pump (12%). Conversely, there are retrospective series showing that when compared to off-pump technique, VA ECMO has reduced PGD rates and improved survival. Because selection bias and unknown confounders in retrospective studies could have been the cause of these conflicting results, part of the ECLS Registry Investigators are committed to a prospective multicenter randomized trial comparing off-pump versus VA ECMO LTx.

Official Title
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Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation VIP BOLT Trial: A Multicenter Prospective Randomized Trial

Conditions
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Lung Transplant

Intervention / Treatment
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* Procedure: Off-pump lung transplantation
* Procedure: Venoarterial ECMO lung transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bilateral Lung Transplantation (LTx) recipients. Mean pulmonary artery pressure < or = 35 mmHg. Eligible for off-pump or VA ECMO based on the judgement of the attending surgeon. Exclusion Criteria: Single lung transplant Multiorgan transplant. Donor after cardiac death (DCD). Re-transplant. Intention to use prophylactic post-operative ECMO. Previous major lung surgery. Video-assisted thoracoscopic surgery (VATS) and wedge resection are not an exclusion criterion. Previous pleurodesis. Preoperative ECMO and/or mechanical ventilation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Off-Pump Bilateral Lung Transplantation<br>Subjects will receive 'off-pump' technique for lung transplantation as part of standard of care | Procedure: Off-pump lung transplantation<br>* General anesthesia, intubation with double lumen tube, thoracotomies or clamshell incision, pneumonectomy starting by the less perfused lung in the scan, stump preparation, lung implantation, reperfusion, gradual release of the pulmonary artery clamp, deairing, ventilation of the 1st implanted lung. The process is repeated at the contralateral side. Ventilation of both lungs, chest closure.<br>|
| Active Comparator: Venoarterial Extra Corporeal Membrane Oxygenation (VA ECMO) Bilateral Lung Transplantation<br>Subjects will receive VA ECMO technique for lung transplantation as part of standard of care | Procedure: Venoarterial ECMO lung transplantation<br>* General anesthesia, intubation with double lumen tube, thoracotomies or clamshell incision, heparin, peripheral or central venoarterial ECMO cannulation, first pneumonectomy, stump preparation, lung implantation, reperfusion, release of the pulmonary artery clamp, deairing, ventilation of the 1st implanted lung. The process is repeated at the contralateral side. Ventilation of both lungs, ECMO decannulation, chest closure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Lung Graft Dysfunction (PGD) grade 3 | Rate of PGD according to the The International Society for Heart and Lung Transplantation (ISHLT) classification | 48-72 hours | 
| Mortality | Death rate of subjects following lung transplantation | 90 days | 
| Primary Lung Graft Dysfunction (PGD) grade 3 and Mortality | Rate of PGD according to the The International Society for Heart and Lung Transplantation (ISHLT) classification plus the Death rate of subjects following lung transplantation | 48-72 hours and 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red blood cell transfusions | Number of subjects to require red blood cell transfusions | Intraoperative plus the first 24 hours in the ICU | 
| Chest tube output | Chest tube output the first 24 hours following lung transplantation reported in cubic centimeter (cc) | First 24 hours | 
| Incidence of re-exploration for bleeding | Number of subject to require re-exploration for bleeding | First 48 hours | 
| Incidence of air emboli | Number of subjects to experience air emboli | During VA ECMO run | 
| Incidence of stroke | Number of subjects to experience stroke | 90 days or discharge from the index hospitalization | 
| Incidence of Primary Lung Graft Dysfunction (PGD) grade 3 | Number of subjects to experience a PGD grade 3 following lung transplantation. PGD will be rated according to the The International Society for Heart and Lung Transplantation (ISHLT) classification | At 0 hours (ICU arrival) and 24 hours | 
| Incidence of pneumonia | Number of subjects to experience pneumonia | 90 days or discharge from the index hospitalization | 
| Incidence of need for dialysis | Number of subjects to need dialysis | 90 days or discharge from the index hospitalization | 
| Incidence of transplant rejection | Number of subjects to experience transplant rejection | 90 days or discharge from the index hospitalization | 
| Incidence of bronchial dehiscence | Number of subjects to experience bronchial dehiscence | 90 days or discharge from the index hospitalization | 
| Incidence of tracheostomy | Number of subjects to require tracheostomy | 90 days or discharge from the index hospitalization | 
| Length of mechanical ventilation | Total amount of time subjects require mechanical ventilation following lung transplantation | 90 days or discharge from the index hospitalization | 
| Length of stay | Total amount of time subjects are hospitalized | 90 days or discharge from the index hospitalization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bilateral