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Veno-arterial ExtraCorporeal Membrane Oxygenation to Reduce Morbidity and Mortality Following Lung TransPlant

Not Applicable
Recruiting
Conditions
The Number of Ventilator-free Days in the 28 Days Following LT
Interventions
Procedure: Veno-arterial extracorporeal membrane oxygenation
Registration Number
NCT05664204
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Systematic ECMOVeno-arterial extracorporeal membrane oxygenationVA-ECMO will be implanted before the first pulmonary artery cross-clamp, in a systematic manner
On-demand ECMOVeno-arterial extracorporeal membrane oxygenationVA-ECMO will be implanted intraoperatively, in an unplanned manner if the hemodynamic and respiratory indices meet pre-planned criteria at different time-points: a PaO2/FiO2 ratio\<100 mmHg or a respiratory acidosis, with pH\< 7.2, PaCO2\>60 mmHg, a mean pulmonary arterial pressure\>50mmHg (or 2/3 of MAP) and/or an acute pulmonal core at trans-esophageal echography monitoring an acute left ventricular dysfunction at trans-esophageal echography monitoring
Primary Outcome Measures
NameTimeMethod
The number of ventilator-free daysThe 28 days following LT

Assess the efficacy of a systematic, pre-operative VA-ECMO strategy on increasing ventilator-free days in the 28 days following LT

Secondary Outcome Measures
NameTimeMethod
Time-to-death from all causesThe first year after LT
Vital statusDay-90 after LT
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, thrombophlebitisThe 28 days following LT, Assessed daily from day-1 to day-90
The occurrence of intraoperative hemodynamic failure;The 28 days following LT

Intra-operative amount of norepinephrine (dose in microg/kg of body weight)

ECMO-free days ; VV or VA-ECMO-free daysThe 28 days following LT
The length of hospital stay; Length of hospital stay in daysat day 90
The occurrence of bronchial complication requiring a bronchoscopic intervention ; Bronchial complications requiring a bronchoscopic interventionFrom LT to 1-year
The occurrence of grade III PGDThe 72 hours following LT
All-cause mortalityDay-90 after LT
The occurrence of post-operative hemodynamic failure ;The 28 days following LT

Norepinephrine-free days (number of days without noradrenaline administration)

Forced expiratory volume during the first second (FEV1)At 1-year
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)The 28 days following LT
The length of intensive care unit stayat day 90

Length of ICU stay in days

The occurrence of acute renal failure;The 28 days following LT

Renal failure KDIGO stage 3

The need of red blood cell transfusionThe 28 days following LT

Number of red blood cell packs administered

Trial Locations

Locations (2)

Hôpital Bichat Claude Bernard

🇫🇷

Paris, France

Hôpital FOCH

🇫🇷

Suresnes, France

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