The Number of Ventilator-free Days in the 28 Days Following LTECMOToPNCT05664204
Veno-arterial ExtraCorporeal Membrane Oxygenation to Reduce Morbidity and Mortality Following Lung TransPlant
A study testing Veno-arterial extracorporeal membrane oxygenation in people with The Number of Ventilator-free Days in the 28 Days Following LT, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- The Number of Ventilator-free Days in the 28 Days Following LT
- What is being tested?
- Veno-arterial extracorporeal membrane oxygenation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 2 sitesFrance
- Study dates
- 29 Feb 2024to 28 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years Assessed for bilateral sequential lung transplantation for obstructive or restrictive lung disease Affiliation to the French social security Written informed consent
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Hôpital Bichat Claude Bernard
Paris, 75018
- Not yet recruiting
Hôpital FOCH
Suresnes, 92 150
Jonathan MESSIKA, MD, +33 1 46 25 59 84, j.messika@hopital-foch.com
About this study
Official title: Veno-arterial Extracorporeal Membrane Oxygenation to Reduce Morbidity and Mortality Following Lung Transplant: a Randomized Controlled Trial
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.
Read the 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
- Being tested
- Veno-arterial extracorporeal membrane oxygenation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Veno-arterial extracorporeal membrane oxygenationProcedure or surgery
Strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events
| Study group | Role | What they receive |
|---|---|---|
| Systematic ECMO | Experimental | VA-ECMO will be implanted before the first pulmonary artery cross-clamp, in a systematic manner Receives: Procedure: Veno-arterial extracorporeal membrane oxygenation |
| On-demand ECMO | Active comparator | 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 Receives: Procedure: Veno-arterial extracorporeal membrane oxygenation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of ventilator-free days
Assess the efficacy of a systematic, pre-operative VA-ECMO strategy on increasing ventilator-free days in the 28 days following LT
Measured: The 28 days following LT
Secondary outcomes (15)
The occurrence of grade III PGD
Measured: The 72 hours following LT
All-cause mortality
Measured: Day-90 after LT
Vital status
Measured: Day-90 after LT
Time-to-death from all causes
Measured: The first year 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, thrombophlebitis
Measured: The 28 days following LT, Assessed daily from day-1 to day-90
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)
Measured: The 28 days following LT
The occurrence of intraoperative hemodynamic failure;
Intra-operative amount of norepinephrine (dose in microg/kg of body weight)
Measured: The 28 days following LT
The occurrence of post-operative hemodynamic failure ;
Norepinephrine-free days (number of days without noradrenaline administration)
Measured: The 28 days following LT
The occurrence of acute renal failure;
Renal failure KDIGO stage 3
Measured: The 28 days following LT
The need of red blood cell transfusion
Number of red blood cell packs administered
Measured: The 28 days following LT
ECMO-free days ; VV or VA-ECMO-free days
Measured: The 28 days following LT
The length of intensive care unit stay
Length of ICU stay in days
Measured: at day 90
The length of hospital stay; Length of hospital stay in days
Measured: at day 90
The occurrence of bronchial complication requiring a bronchoscopic intervention ; Bronchial complications requiring a bronchoscopic intervention
Measured: From LT to 1-year
Forced expiratory volume during the first second (FEV1)
Measured: At 1-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2022
- Study start29 Feb 2024
- Primary completion2 Feb 2027 (estimated)
- Study completion28 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for The Number of Ventilator-free Days in the 28 Days Following LTStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jonathan MESSIKA, MD, Principal investigator, Hôpital FOCH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05664204
- Sponsor's protocol ID
- APHP211037
- Other IDs
- 2022-A00538-35
- Acronym
- ECMOToP
- Status last verified
- May 2024
- First submitted
- 7 Dec 2022
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: participant-level deidentified dataset
Publications
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.
PubMed 38448059
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Veno-arterial Extracorporeal Membrane Oxygenation to Reduce Morbidity and Mortality Following Lung Transplant: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05664204
- Acronym / sponsor ID
- ECMOToP / APHP211037
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 29 Feb 2024 (actual)
- Primary completion
- 2 Feb 2027 (estimated)
- Study completion
- 28 Sep 2027 (estimated)
- First posted
- 23 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systematic ECMO | Experimental | Procedure: Veno-arterial extracorporeal membrane oxygenationVA-ECMO will be implanted before the first pulmonary artery cross-clamp, in a systematic manner |
| On-demand ECMO | Active comparator | Procedure: Veno-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age >18 years Assessed for bilateral sequential lung transplantation for obstructive or restrictive lung disease Affiliation to the French social security Written informed consent
Key exclusion criteria (16 listed)
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Veno-arterial extracorporeal membrane oxygenationStrategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events | Procedure or surgery | On-demand ECMO, Systematic ECMO |
Primary outcome
The number of ventilator-free days
Time frame: The 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
15 secondary outcomes
The occurrence of grade III PGD
Time frame: The 72 hours following LT
All-cause mortality
Time frame: Day-90 after LT
Vital status
Time frame: Day-90 after LT
Time-to-death from all causes
Time frame: The first year 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, thrombophlebitis
Time frame: The 28 days following LT, Assessed daily from day-1 to day-90
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)
Time frame: The 28 days following LT
The occurrence of intraoperative hemodynamic failure;
Time frame: The 28 days following LT
The occurrence of post-operative hemodynamic failure ;
Time frame: The 28 days following LT
The occurrence of acute renal failure;
Time frame: The 28 days following LT
The need of red blood cell transfusion
Time frame: The 28 days following LT
ECMO-free days ; VV or VA-ECMO-free days
Time frame: The 28 days following LT
The length of intensive care unit stay
Time frame: at day 90
The length of hospital stay; Length of hospital stay in days
Time frame: at day 90
The occurrence of bronchial complication requiring a bronchoscopic intervention ; Bronchial complications requiring a bronchoscopic intervention
Time frame: From LT to 1-year
Forced expiratory volume during the first second (FEV1)
Time frame: At 1-year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Derived from this study: PubMed 38448059Messika 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.
- Individual participant dataSharing planned: Yes. participant-level deidentified dataset
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonathan MESSIKA, MD principal investigator
Hôpital FOCH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Veno-arterial extracorporeal membrane oxygenation in people with The Number of Ventilator-free Days in the 28 Days Following LT, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jonathan MESSIKA, MD (+33 1 46 25 59 84, j.messika@hopital-foch.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of ventilator-free days (time frame: The 28 days following LT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05664204, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.