Inhaled Isoflurane for Sedation of Invasively Ventilated Patients With Cardiogenic Shock on Extracorporeal Membrane Oxygenation

NCT07099014 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: APHP2308442023-510261-94-00
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Cardiogenic Shock, ECMO

Keywords

Cardiogenic shock, ECMO

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 28

Secondary Outcomes (16)

• Overall survival

  Day 28

• Number of ECMO-free days

  Day 14, Day 28

• Number of inotropes-free days

  Day 14, Day 28

• Number of ICU-free days

  Day 28

• Number of ventilation-free days

  Day 14, Day 28

Study Arms (2)

Inhaled ISOFLURANE

EXPERIMENTAL

Initial rate of 3 mL/h given for up to 14 days or until extubation

Drug: Inahled Isoflurane

Propofol +/- Midazolam

ACTIVE COMPARATOR

Propofol final dose 4 mg/kg/h +/- Midazolam, maximal dose 0,2 mg/kg/h

Drug: Propofol, midazolam

Interventions

Inahled Isoflurane DRUG

treatment administration

Inhaled ISOFLURANE

Propofol, midazolam DRUG

treatment administration

Propofol +/- Midazolam

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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
• Contraindication or allergies to isoflurane, propofol, midazolam or other halogenated anaesthetics

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Related Publications (1)

• 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.

  PMID: 34454654 BACKGROUND

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

Propofol; Midazolam

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Matthieu SCHMIDT, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Central Study Contacts

Juliette CHOMMELOUX, MD

CONTACT

330142162909; juliette.chommeloux@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2025
• First Posted: August 1, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): October 13, 2028
• Study Completion (Estimated): April 13, 2029
• Last Updated: August 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal