Clinical trial NCT05664204: Veno-arterial ExtraCorporeal Membrane Oxygenation to Reduce Morbidity and Mortality Following Lung TransPlant
Official title: Veno-arterial Extracorporeal Membrane Oxygenation to Reduce Morbidity and Mortality Following Lung Transplant: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: The Number of Ventilator-free Days in the 28 Days Following LT
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-12-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: In patients undergoing lung transplantation (LT), the investigators hypothesize that a "systematic" intraoperative ECMO strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events, as compared to an "on-demand" intraoperative ECMO strategy.

To date, LT remains a highly hazardous procedure. Even if the surgical procedure is well established, the intraoperative support is not, and most intra-operative ECMO decisions rely on local protocols, anesthesiologists' habits, and surgeons' preference.

The efficacy of applying a "systematic" strategy on reducing the occurrence of severe primary graft dysfunction and thus mechanical ventilation in the 28 days following LT, without increasing mortality or morbidity, would support future guidelines on the use of ECMO in the intraoperative period of LT for obstructive and restrictive lung diseases.

Detailed description: Lung transplantation (LT) provides the prospect of improved survival and quality of life for patients with end stage lung and pulmonary vascular diseases. Its performance carries significant adverse effects, being either intra- or postoperative. The ventilation of a diseased lung for sometimes extended periods and the risk of reperfusion oedema and primary graft dysfunction is a challenge. Moreover, significant hemodynamic instabilities episodes might occur, because of pressure on, or displacement of the heart, clamping of the pulmonary arteries and ischemia-reperfusion syndrome. veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has now replaced cardiopulmonary bypass for respiratory and hemodynamic intraoperative support, carrying less side effects, and an improved early survival.

Even though ECMO is a widely used technique, no precise guideline exists on the hemodynamic and respiratory indexes in LT settings to initiate intraoperative ECMO, but only experts' opinion. Besides, it has to be underlined that the rate of LT performed in the absence of any mechanical support is highly variable among centres, ranging from being exceptional up to 70%.

The investigators aim at evaluating two strategies of ECMO initiation in the pre- and intraoperative periods in patients with pulmonary disease requiring LT: an "on-demand" strategy, in which VA-ECMO will be initiated on high hemodynamic and respiratory needs thresholds and a "systematic" strategy in which VA-ECMO will be pre-emptively initiated.

The investigators hypothesize that a "systematic" strategy allows to reduce the risk of severe primary graft dysfunction and the need for mechanical ventilator in the 28 days following LT without increasing adverse events

Eligibility criteria: Inclusion Criteria:

Age \>18 years Assessed for bilateral sequential lung transplantation for obstructive or restrictive lung disease Affiliation to the French social security Written informed consent

Exclusion Criteria:

At listing :

* a pulmonary hypertension with a mPAP \> 45 mmHg, including in the absence of haemodynamic collapse (MAP, LVEF, RV function all normal)
* a pulmonary hypertension with echocardiographic evidences of right heart dysfunction (paradoxical septum or RV dilatation or RVEF \< 35%)
* a pre-capillary pulmonary hypertension at right heart catheterization with low cardiac output

  * LT for primary pulmonary hypertension
  * LT for cystic fibrosis and graft-vs-host disease
  * Re-do LT
  * Combined multi-organ transplantation
  * Active malignancy
  * Pregnancy, breastfeeding
  * Patients under guardianship (tutelle, curatelle, sauvegarde de justice)

Socondary exclusion criteria:

Patients without pulmonary hypertension or with pulmonary hypertension without right ventricular dilatation on an echocardiography in the last 6 months will be randomized; Patients meeting one of the following criteria will not be randomized and will be secondary excluded from the study :

* preoperative severe pulmonary hypertension with hemodynamic collapse on echocardiography defined by: paradoxical septum or dilatation of the right ventricle or RVEF \< 20LT in a patient under ECMO as bridge-to-transplantation
* PreLT hypoxemia with PaO2/FiO2 \< 80mmHg
* PreLT hypercapnia PaCO2 \> 80 mmHg after induction

Primary outcomes:
measure: The number of ventilator-free days
timeFrame: The 28 days following LT
Secondary outcomes:
measure: The occurrence of grade III PGD
timeFrame: The 72 hours following LT
measure: All-cause mortality
timeFrame: Day-90 after LT
measure: Vital status
timeFrame: Day-90 after LT
measure: Time-to-death from all causes
timeFrame: The first year after LT
measure: The occurrence of ECMO-associated adverse event ; ECMO-associated adverse event defined as cannula infection, misplacement, intra-operative or per-ECMO air-embolism, limb ischemia, vascular complications, thrombophlebitis
timeFrame: The 28 days following LT, Assessed daily from day-1 to day-90
measure: The occurrence of ventilator associated pneumonia (VAP) ; Occurrence of VAP (microbiologically confirmed pneumonia occurring under invasive ventilation 21 and after 48 hours of invasive ventilation)
timeFrame: The 28 days following LT
measure: The occurrence of intraoperative hemodynamic failure;
timeFrame: The 28 days following LT
measure: The occurrence of post-operative hemodynamic failure ;
timeFrame: The 28 days following LT
measure: The occurrence of acute renal failure;
timeFrame: The 28 days following LT
measure: The need of red blood cell transfusion
timeFrame: The 28 days following LT
measure: ECMO-free days ; VV or VA-ECMO-free days
timeFrame: The 28 days following LT
measure: The length of intensive care unit stay
timeFrame: at day 90
measure: The length of hospital stay; Length of hospital stay in days
timeFrame: at day 90
measure: The occurrence of bronchial complication requiring a bronchoscopic intervention ; Bronchial complications requiring a bronchoscopic intervention
timeFrame: From LT to 1-year
measure: Forced expiratory volume during the first second (FEV1)
timeFrame: At 1-year
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat Claude Bernard
city: Suresnes
country: France
facility: Hôpital FOCH
Study officials:
affiliation: Hôpital FOCH
name: Jonathan MESSIKA, MD
role: PRINCIPAL_INVESTIGATOR
References: