Cardiogenic Shock, ECMOPhase 3INSEPTIONNCT07099014
Inhaled Isoflurane for Sedation of Invasively Ventilated Patients With Cardiogenic Shock on Extracorporeal Membrane Oxygenation
A Phase 3 study testing Inahled Isoflurane and Propofol, midazolam in people with Cardiogenic Shock, ECMO, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Midazolam and propofol are the most used intravenous (IV) sedative agents, but their use is associated with well-known adverse effects such as accumulation, myotoxicity, tachyphylaxis, and unpredictable wake-up time. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cardiogenic Shock, ECMO
- What is being tested?
- Inahled Isoflurane and Propofol, midazolam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 15 Sep 2025to 13 Apr 2029
- Phase
- Phase 3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cardiogenic shock on VA ECMO support for less than 24 hours
- Patients on invasive mechanical ventilation receiving propofol and/or midazolam at the time of randomization
- Invasive mechanical ventilation for less than 48 hours
- Expected invasive ventilation and sedation for at least 24h, with a prescribed Richmond agitation scale target within the range of -1 to - 4
- Social security registration (AME excluded)
Who cannot join
- Age <18 and >75
- Pregnancy or breastfeeding
- Initiation of ECMO >24 hours
- Initiation of mechanical ventilation >48 hours
- Cardiopulmonary Resuscitation >20 minutes before randomization
- Patient moribund on the day of randomization, SAPS II >90
Show all 12Show fewer
- Suspected or proven intracranial hypertension
- Corrected QT interval > 450ms or with a known or suspected genetic predisposition to malignant hyperthermia
- Chronic liver disease defined as a Child-Pugh score of 12-15
- Patients ventilated with a tidal volume < 4ml/kg predicted body weight
- Participation in another interventional study or being in the exclusion period at the end of a previous study.
- Contraindication or allergies to isoflurane, propofol, midazolam or other halogenated anaesthetics
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Midazolam and propofol are the most used intravenous (IV) sedative agents, but their use is associated with well-known adverse effects such as accumulation, myotoxicity, tachyphylaxis, and unpredictable wake-up time.
For benzodiazepines, an increased tolerance, possible accumulation after long-term use, and an increased risk of acute withdrawal syndrome are reported. In patients on extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, the negative hemodynamic effects of these drugs are a particular matter of concern. Besides the extracorporeal circuit itself may affect the pharmacokinetics of these IV sedatives. Indeed, drug sequestration in ECMO circuits is a well-known phenomenon influenced by drug chemo-physical properties. Given the large surface area of tubing and membrane, considerable quantities of drugs used in ECMO patients may be sequestered over a period, resulting in a significant increase in their volume of distribution. Similarly, frequent hemodilution and organ dysfunction would also contribute to an increase in the volume of distribution.
Read more
Propofol, which is lipophilic is significantly sequestrated in the circuit. Consequently, it is commonly observed that patients receiving ECMO have substantially higher sedative and analgesic drug requirements than patients without ECMO.
To date, there is no ideal concept for analgesia and sedation of patients on ECMO in the ICU.
A drug that sedates effectively but with minimal residual sedation after the end of the administration and without the aforementioned drawbacks of the current agents would be valuable.
Interestingly, a recent randomized controlled non-inferiority trial that randomized 338 patients showed that, compared with propofol, sedation with inhaled anaesthetics was non-inferior. Sedation with inhaled anaesthetics resulted in a higher rate of spontaneous breathing and a shorter wake-up time after 48h of sedation. Indeed, inhaled sedation, which has been associated with reduced opioid consumption and less delirium in ICU patients, is a promising alternative to IV sedation. Moreover, inhaled anaesthetics might be associated with less myocardial injury and lower doses of inotropic support in patients undergoing cardiac surgery. However, to date, the experience with volatile agents remains limited in patients on ECMO.
We hypothesized that the use of inhaled isoflurane with the Sedaconda anaesthetics conserving device (ACD) in cardiogenic shock patients on ECMO will reduce the mortality and increase the number of ventilation-free days at day 28 following ECMO onset compared to usual IV sedation by propofol and/or midazolam.
- Conditions
- Cardiogenic Shock, ECMO
- Being tested
- Inahled Isoflurane, Propofol, midazolam
- Keywords
- Cardiogenic shock, ECMO
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inahled IsofluraneDrug
treatment administration
Propofol, midazolamDrug
treatment administration
| Study group | Role | What they receive |
|---|---|---|
| Inhaled ISOFLURANE | Experimental | Initial rate of 3 mL/h given for up to 14 days or until extubation Receives: Drug: Inahled Isoflurane |
| Propofol +/- Midazolam | Active comparator | Propofol final dose 4 mg/kg/h +/- Midazolam, maximal dose 0,2 mg/kg/h Receives: Drug: Propofol, midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
A composite hierarchical outcome composed of two components: 1) mortality, 2) number of days alive without invasive mechanical ventilation within 28 days following ECMO initiation
- Each patient will be compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better.
- If one patient survived on day 28 and the other did not, scores of +1 and -1 will be assigned, respectively, for that pairwise comparison. If both patients in the pairwise comparison survived at day 28, the assigned score will depend on which patient had more days free from mechanical ventilation: the patient with more ventilator-free days alive at day 28 will receive a score of +1, while the patient with fewer days will receive a score of -1. If both patients survived and had the same number of ventilator-free days on day 28, and if both patients died, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score.
Measured: Day 28
Secondary outcomes (16)
Overall survival
Measured: Day 28
Number of ECMO-free days
Measured: Day 14, Day 28
Number of inotropes-free days
Measured: Day 14, Day 28
Number of ICU-free days
Measured: Day 28
Number of ventilation-free days
Measured: Day 14, Day 28
incidence of delirium
Measured: Day 28
Opioids daily consumption during invasive mechanical ventilation
Measured: Day 14
Consumption of propofol
consumption during invasive mechanical ventilation
Measured: Day 14
Consumption of midazolam
consumption during invasive mechanical ventilation
Measured: Day 14
Consumption of Clonidine
consumption during invasive mechanical ventilation
Measured: Day 14
Consumption of Haloperidol
consumption during invasive mechanical ventilation
Measured: Day 14
Consumption of dexmedetomidine
consumption during invasive mechanical ventilation
Measured: Day 14
Incidence of drugs side effects (refractory hypertension, malignant hyperthermia)
assess the safety of prolonged isoflurane inhalation during ECMO
Measured: From randomization to Day 28
Number of participants requiring ventricular assist device
Measured: Day 28
Number of participants undergoing heart transplantation
Measured: Day 28
Rate of side effects possibly linked to ineffective sedation (self-extubation, accidental ECMO decannulation, catheter withdrawal)
Measured: From randomization to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start15 Sep 2025 (estimated)
- Primary completion13 Oct 2028 (estimated)
- Study completion13 Apr 2029 (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 Cardiogenic Shock, ECMOStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthieu SCHMIDT, MD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07099014
- Sponsor's protocol ID
- APHP230844
- Other IDs
- 2023-510261-94-00, 2023
- Acronym
- INSEPTION
- Status last verified
- Jun 2025
- First submitted
- 16 Jul 2025
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Publications
Meiser A, Volk T, Wallenborn J, Guenther U, Becher T, Bracht H, Schwarzkopf K, Knafelj R, Faltlhauser A, Thal SC, Soukup J, Kellner P, Druner M, Vogelsang H, Bellgardt M, Sackey P; Sedaconda study group. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021 Nov;9(11):1231-1240. doi: 10.1016/S2213-2600(21)00323-4. Epub 2021 Aug 26.
PubMed 34454654
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Isoflurane for Sedation of Invasively Ventilated Patients With Cardiogenic Shock on Extracorporeal Membrane Oxygenation
- ClinicalTrials.gov ID
- NCT07099014
- Acronym / sponsor ID
- INSEPTION / APHP230844
- Conditions
- Cardiogenic Shock, ECMO
- Keywords
- Cardiogenic shock, ECMO
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 15 Sep 2025 (estimated)
- Primary completion
- 13 Oct 2028 (estimated)
- Study completion
- 13 Apr 2029 (estimated)
- First posted
- 1 Aug 2025 (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.
Midazolam and propofol are the most used intravenous (IV) sedative agents, but their use is associated with well-known adverse effects such as accumulation, myotoxicity, tachyphylaxis, and unpredictable wake-up time.
For benzodiazepines, an increased tolerance, possible accumulation after long-term use, and an increased risk of acute withdrawal syndrome are reported. In patients on extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, the negative hemodynamic effects of these drugs are a particular matter of concern. Besides the extracorporeal circuit itself may affect the pharmacokinetics of these IV sedatives. Indeed, drug sequestration in ECMO circuits is a well-known phenomenon influenced by drug chemo-physical properties. Given the large surface area of tubing and membrane, considerable quantities of drugs used in ECMO patients may be sequestered over a period, resulting in a significant increase in their volume of distribution. Similarly, frequent hemodilution and organ dysfunction would also contribute to an increase in the volume of distribution.
Propofol, which is lipophilic is significantly sequestrated in the circuit. Consequently, it is commonly observed that patients receiving ECMO have substantially higher sedative and analgesic drug requirements than patients without ECMO.
To date, there is no ideal concept for analgesia and sedation of patients on ECMO in the ICU.
A drug that sedates effectively but with minimal residual sedation after the end of the administration and without the aforementioned drawbacks of the current agents would be valuable.
Interestingly, a recent randomized controlled non-inferiority trial that randomized 338 patients showed that, compared with propofol, sedation with inhaled anaesthetics was non-inferior. Sedation with inhaled anaesthetics resulted in a higher rate of spontaneous breathing and a shorter wake-up time after 48h of sedation. Indeed, inhaled sedation, which has been associated with reduced opioid consumption and less delirium in ICU patients, is a promising alternative to IV sedation. Moreover, inhaled anaesthetics might be associated with less myocardial injury and lower doses of inotropic support in patients undergoing cardiac surgery. However, to date, the experience with volatile agents remains limited in patients on ECMO.
We hypothesized that the use of inhaled isoflurane with the Sedaconda anaesthetics conserving device (ACD) in cardiogenic shock patients on ECMO will reduce the mortality and increase the number of ventilation-free days at day 28 following ECMO onset compared to usual IV sedation by propofol and/or midazolam.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled ISOFLURANE | Experimental | Drug: Inahled IsofluraneInitial rate of 3 mL/h given for up to 14 days or until extubation |
| Propofol +/- Midazolam | Active comparator | Drug: Propofol, midazolamPropofol final dose 4 mg/kg/h +/- Midazolam, maximal dose 0,2 mg/kg/h |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Cardiogenic shock on VA ECMO support for less than 24 hours
- Patients on invasive mechanical ventilation receiving propofol and/or midazolam at the time of randomization
- Invasive mechanical ventilation for less than 48 hours
- Expected invasive ventilation and sedation for at least 24h, with a prescribed Richmond agitation scale target within the range of -1 to - 4
- Social security registration (AME excluded)
Key exclusion criteria (12 listed)
- Age <18 and >75
- Pregnancy or breastfeeding
- Initiation of ECMO >24 hours
- Initiation of mechanical ventilation >48 hours
- Cardiopulmonary Resuscitation >20 minutes before randomization
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 |
|---|---|---|
| Inahled Isofluranetreatment administration | Drug | Inhaled ISOFLURANE |
| Propofol, midazolamtreatment administration | Drug | Propofol +/- Midazolam |
Primary outcome
A composite hierarchical outcome composed of two components: 1) mortality, 2) number of days alive without invasive mechanical ventilation within 28 days following ECMO initiation
Time frame: Day 28
* Each patient will be compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better. * If one patient survived on day 28 and the other did not, scores of +1 and -1 will be assigned, respectively, for that pairwise comparison. If both patients in the pairwise comparison survived at day 28, the assigned score will depend on which patient had more days free from mechanical ventilation: the patient with more ventilator-free days alive at day 28 will receive a score of +1, while the patient with fewer days will receive a score of -1. If both patients survived and had the same number of ventilator-free days on day 28, and if both patients died, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score.
16 secondary outcomes
Overall survival
Time frame: Day 28
Number of ECMO-free days
Time frame: Day 14, Day 28
Number of inotropes-free days
Time frame: Day 14, Day 28
Number of ICU-free days
Time frame: Day 28
Number of ventilation-free days
Time frame: Day 14, Day 28
incidence of delirium
Time frame: Day 28
Opioids daily consumption during invasive mechanical ventilation
Time frame: Day 14
Consumption of propofol
Time frame: Day 14
Consumption of midazolam
Time frame: Day 14
Consumption of Clonidine
Time frame: Day 14
Consumption of Haloperidol
Time frame: Day 14
Consumption of dexmedetomidine
Time frame: Day 14
Incidence of drugs side effects (refractory hypertension, malignant hyperthermia)
Time frame: From randomization to Day 28
Number of participants requiring ventricular assist device
Time frame: Day 28
Number of participants undergoing heart transplantation
Time frame: Day 28
Rate of side effects possibly linked to ineffective sedation (self-extubation, accidental ECMO decannulation, catheter withdrawal)
Time frame: From randomization to Day 28
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 1 Aug 2025.
- Background: PubMed 34454654Meiser A, Volk T, Wallenborn J, Guenther U, Becher T, Bracht H, Schwarzkopf K, Knafelj R, Faltlhauser A, Thal SC, Soukup J, Kellner P, Druner M, Vogelsang H, Bellgardt M, Sackey P; Sedaconda study group. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021 Nov;9(11):1231-1240. doi: 10.1016/S2213-2600(21)00323-4. Epub 2021 Aug 26.
- Individual participant dataSharing planned: Yes. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
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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.
Matthieu SCHMIDT, MD study director
Assistance Publique - Hôpitaux de Paris
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Inahled Isoflurane and Propofol, midazolam in people with Cardiogenic Shock, ECMO, run by Assistance Publique - Hôpitaux de Paris.
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 5 inclusion and 12 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: opening soon, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Juliette CHOMMELOUX, MD (330142162909, juliette.chommeloux@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite hierarchical outcome composed of two components: 1) mortality, 2) number of days alive without invasive mechanical ventilation within 28 days following ECMO initiation (time frame: Day 28). 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 NCT07099014, 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 1 Aug 2025.