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

NCT ID: NCT05664204

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-29
• Study Completion Date: 2027-09-28

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

Conditions

The Number of Ventilator-free Days in the 28 Days Following LT

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Systematic ECMO

VA-ECMO will be implanted before the first pulmonary artery cross-clamp, in a systematic manner

Group Type: EXPERIMENTAL

Veno-arterial extracorporeal membrane oxygenation

Intervention Type: PROCEDURE

Strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events

On-demand ECMO

VA-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

Group Type: ACTIVE_COMPARATOR

Veno-arterial extracorporeal membrane oxygenation

Intervention Type: PROCEDURE

Strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events

Interventions

Veno-arterial extracorporeal membrane oxygenation

Strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events

Intervention Type: PROCEDURE

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan MESSIKA, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital FOCH

Locations

Hôpital Bichat Claude Bernard

Paris, , France

Site Status: RECRUITING

Hôpital FOCH

Suresnes, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Jonathan MESSIKA, MD

Role: CONTACT

j.messika@hopital-foch.com

+33 1 46 25 59 84

Facility Contacts

Jonathan MESSIKA, MD

Role: primary

j.messika@hopital-foch.com

+33 1 46 25 59 84

References

Messika J, Eloy P, Boulate D, Charvet A, Fessler J, Jougon J, Lacoste P, Mercier O, Portran P, Roze H, Sage E, Thes J, Tronc F, Vourc'h M, Montravers P, Castier Y, Mal H, Mordant P; Investigators from the ECMOToP Study group. Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial. BMJ Open. 2024 Mar 5;14(3):e077770. doi: 10.1136/bmjopen-2023-077770.

Reference Type: DERIVED

PMID: 38448059 (View on PubMed)

Other Identifiers

2022-A00538-35

Identifier Type: OTHER

Identifier Source: secondary_id

APHP211037

Identifier Type: -

Identifier Source: org_study_id