Inhaled isoflurane for SEdation of invasively ventilated PaTIents with cardiogenic shock on extracOrporeal membrane oxygeNation (INSEPTION)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

26 Apr 2026 → ongoing

Decision date (initial)

2025-05-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Organisation name Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévent

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess in cardiogenic shock patients on VA-ECMO the efficacy of inhaled isoflurane via the anesthetic conserving device, on a composite outcome of mortality and the number of ventilator-free days at day 28 following ECMO onset.

Secondary objectives 9

1. To assess the efficacy of inhaled isoflurane on Mortality within day 28
2. To assess the efficacy of inhaled isoflurane on duration of ECMO and inotropes support
3. To assess the efficacy of inhaled isoflurane on ICU lenght of stay
4. To assess the efficacy of inhaled isoflurane on mechanical ventilation duration
5. To assess the efficacy of inhaled isoflurane on delirium
6. To assess the efficacy of inhaled isoflurane on opioids daily consumption during invasive mechanical ventilation
7. To assess the efficacy of inhaled isoflurane on consumtion of propofol, midazolam, clonidine, haloperidol or dexmedetomidine consumption during invasive mechanical ventilation
8. To assess the safety of prolonged isoflurane inhalation during ECMO
9. To assess the effect of inhaled isoflurane on the ventilator and delirium-free days in predefined subgroups of patients (those with pre-ECMO cardiac arrest or suffering from acute myocardial infarction)

Conditions and MedDRA coding

Adult patients with severe cardiogenic shock on venoarterial ECMO support for less than 24 hours.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Cardiogenic shock on VA ECMO support for less than 24 hours
2. Patients on invasive mechanical ventilation receiving propofol and/or midazolam at the time of randomization
3. Invasive mechanical ventilation for less than 48 hours
4. Expected invasive ventilation and sedation for at least 24h, with a prescribed Richmond agitation scale target within the range of -1 to - 4
5. Social security registration (AME excluded)

Exclusion criteria 12

1. Age <18 and >75
2. Patients ventilated with a tidal volume < 4ml/kg predicted body weight
3. Participation in another interventional study or being in the exclusion period at the end of a previous study.
4. Contraindication or allergies to isoflurane, propofol, midazolam or other halogenated anaesthetics
5. Pregnancy or breastfeeding
6. Initiation of ECMO >24 hours
7. Initiation of mechanical ventilation >48 hours
8. Cardiopulmonary Resuscitation >20 minutes before randomization
9. Patient moribund on the day of randomization, SAPS II >90
10. Suspected or proven intracranial hypertension
11. Corrected QT interval > 450ms or with a known or suspected genetic predisposition to malignant hyperthermia
12. Chronic liver disease defined as a Child-Pugh score of 12-15

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A composite outcome of mortality and number of days alive without invasive mechanical ventilation within 28 days following ECMO initiation (detail in protocol)

Secondary endpoints 16

1. Overall survival within 28 days
2. Ventricular assist device or/and heart transplant on day 28
3. Number of ECMO-free days on day 14 and day 28
4. Number of inotropes-free days on day 14 and day 28
5. Number of ICU-free days on day 28
6. Number of ventilation-free days on day 14 and day 28
7. Delirium-free days (evaluated with Confusion Assessment Method for the ICU [CAM-ICU]) on day 14 and day 28
8. Daily morphine equivalent dose during mechanical ventilation until day 14
9. Daily propofol, and midazolam doses during mechanical ventilation until day 14
10. Daily propofol or midazolam bolus needed to achieve the prescribed sedation range until day 14
11. Daily neuroleptics need until day 14
12. Daily clonidine needs until day 14
13. Daily dexmedetomidine need until day 14
14. Rate of side effects possibly linked to ineffective sedation (self-extubation, accidental ECMO decannulation, catheter withdrawal, etc.)
15. Incidence of drugs side effects (refractory hypertension, malignant hyperthermia)
16. Primary and secondary endpoints in predefined subgroups: patients with pre-ECMO cardiac arrest, and patients with acute myocardial infarction.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications