Sevoflurane Sedation in Patients With Septic Shock

NCT ID: NCT03643367

Last Updated: 2025-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2027-11-30

Brief Summary

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Recent in vivo studies from others as well as the investigators group demonstrated that volatile anesthetics immunomodulate sepsis and improve outcome. Also, several clinical trials have convincingly shown that application of a volatile anesthetic provides protection in patients undergoing major surgery.

Patients with sepsis are intubated and ventilated and therefore need sedation. So far, most ICU centers use intravenously applied sedatives in these patients. In the proposed study, we will switch sedation from an intravenous to a volatile anesthetic for a short period of time to explore if sepsis markers improve within the following 120 hours upon sevoflurane conditioning.

Detailed Description

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This randomized controlled trial (RCT) will be conducted over a period of 48 months, to investigate if volatile anesthetics have a positive effect on the prognostic sepsis marker IL-6. All patients with septic shock are intubated, ventilated and sedated with an intravenous anesthetic. In this study, eligible patients diagnosed with septic shock will be randomized 1:1 to the 'volatile group' with interruption of the propofol infusion, followed by a 4-hour sedation with the volatile anesthetic sevoflurane, or a continuous intravenous sedation ('intravenous' =control group). In both groups, 'intravenous' and 'volatile', the inflammatory markers as well as clinical parameters will be determined. The investigators will explore if there is a difference between the course of sepsis markers of the two groups within 5 days after intervention in favor of the volatile group.

Conditions

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Shock, Septic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients with septic shock are intubated and ventilated and therefore need sedation. So far, most ICU centers use intravenously applied sedatives in these patients. In the proposed study, we will switch sedation from an intravenous to a volatile anesthetic for a short period of time (4 hours) to explore if sepsis markers improve within the following 120 hours upon sevoflurane conditioning.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Patients will not be informed about their group assignments, technicians, processing the samples, will not have any access to ICU or patient charts (= double blind trial)

Study Groups

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Sevoflurane Sedation

Patients randomized into experimental group will be treated with sevoflurane during 4 hours

Group Type EXPERIMENTAL

Sevoflurane

Intervention Type DRUG

Included patients, randomized in experimental group, intravenous sedation will be interrupted and followed by a 4 hour sedation with the volatile anesthetic sevoflurane.

Propofol Sedation

Patients randomized into Control Group will get continued intravenous sedation with propofol

Group Type ACTIVE_COMPARATOR

Control Group

Intervention Type DRUG

Included patients randomized in control group, intravenouse sedation is continued with propofol

Interventions

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Sevoflurane

Included patients, randomized in experimental group, intravenous sedation will be interrupted and followed by a 4 hour sedation with the volatile anesthetic sevoflurane.

Intervention Type DRUG

Control Group

Included patients randomized in control group, intravenouse sedation is continued with propofol

Intervention Type DRUG

Other Intervention Names

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Propofol

Eligibility Criteria

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Inclusion Criteria

* Male and female patients, age 18 to 80 years
* Intensive care Unit (ICU) patients with septic shock (despite fluid resuscitation vasopressors needed to maintain mean arterial pressure ≥65 millimeter of mercury (mmHg), and serum lactate \>2mmol/l even with fluid application)
* Treatment of septic shock on ICU with vasopressors not longer than 12 hours
* Sedation and mechanical ventilation on ICU
* Female patients of childbearing potential with negative pregnancy test
* Informed Consent as documented by signature

Exclusion Criteria

* Previous surgery and/or anesthesia (within last 7 days)
* Application of nitric oxide (NO)
* Suspected or known intolerance by history to volatile anesthetics (malignant hyperthermia)
* Immunosuppressive agents
* Systemic corticosteroids in the phase before hospitalization (\> 10mg/d prednisone)
* Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, decompensated heart failure, acute pulmonary edema, major cardiac arrhythmia, seizure, burn, chronic kidney disease, end stage liver failure, neuromuscular disease)
* AIDS
* Autoimmune disease
* Organ transplant
* Subject with active malignancy receiving
* chemotherapy or radiation treatment within last 60 days
* Hepatitis B/C virus infection
* Anti-tumor necrosis factor (TNF) therapy
* Pregnancy and/or Breast feeding
* Use of cytokine absorber
* Enrollment in any other clinical trial during the course of this trial, 30 days prior to its beginning or 30 days after its completion
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kantonsspital Münsterlingen

OTHER

Sponsor Role collaborator

Triemli Hospital

OTHER

Sponsor Role collaborator

Waid City Hospital, Zurich

OTHER

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Schlaepfer, PD

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

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Kantonasspital Münsterlingen

Münsterlingen, , Switzerland

Site Status

Stadtspital Triemli

Zurich, , Switzerland

Site Status

University Hospital of Zurich

Zurich, , Switzerland

Site Status

Waidspital Zürich

Zurich, , Switzerland

Site Status

Countries

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Switzerland

Central Contacts

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Martin Schlaepfer, PD

Role: CONTACT

+41 44 255 4690

Martin Schläpfer, PD

Role: CONTACT

+41 44 255 4690

Facility Contacts

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Thomas Neff, PD Dr. med.

Role: primary

071 686 2108

Patricia Fodor, KD Dr. med.

Role: primary

+41444165202

Martin Schlaepfer, PD Dr med

Role: primary

+41442551111

Beatrice Beck Schimmer, Prof Dr med

Role: backup

Christian Giambarba, Dr. med.

Role: primary

+41443662021

References

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Tang BM, McLean AS, Dawes IW, Huang SJ, Lin RC. The use of gene-expression profiling to identify candidate genes in human sepsis. Am J Respir Crit Care Med. 2007 Oct 1;176(7):676-84. doi: 10.1164/rccm.200612-1819OC. Epub 2007 Jun 15.

Reference Type BACKGROUND
PMID: 17575094 (View on PubMed)

Lu Y, Wang J, Yan J, Yang Y, Sun Y, Huang Y, Hu R, Zhang Y, Jiang H. Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region. Biomed Pharmacother. 2015 Apr;71:139-45. doi: 10.1016/j.biopha.2015.02.032. Epub 2015 Mar 3.

Reference Type BACKGROUND
PMID: 25960229 (View on PubMed)

Klag T, Cantara G, Sechtem U, Athanasiadis A. Interleukin-6 Kinetics can be Useful for Early Treatment Monitoring of Severe Bacterial Sepsis and Septic Shock. Infect Dis Rep. 2016 Mar 21;8(1):6213. doi: 10.4081/idr.2016.6213. eCollection 2016 Mar 21.

Reference Type BACKGROUND
PMID: 27103972 (View on PubMed)

Rios-Toro JJ, Marquez-Coello M, Garcia-Alvarez JM, Martin-Aspas A, Rivera-Fernandez R, Saez de Benito A, Giron-Gonzalez JA. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock. PLoS One. 2017 Apr 5;12(4):e0175254. doi: 10.1371/journal.pone.0175254. eCollection 2017.

Reference Type BACKGROUND
PMID: 28380034 (View on PubMed)

Tschaikowsky K, Hedwig-Geissing M, Braun GG, Radespiel-Troeger M. Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care. 2011 Feb;26(1):54-64. doi: 10.1016/j.jcrc.2010.04.011. Epub 2010 Jun 19.

Reference Type BACKGROUND
PMID: 20646905 (View on PubMed)

Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485.

Reference Type BACKGROUND
PMID: 27483065 (View on PubMed)

Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K; International Forum of Acute Care Trialists. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016 Feb 1;193(3):259-72. doi: 10.1164/rccm.201504-0781OC.

Reference Type BACKGROUND
PMID: 26414292 (View on PubMed)

Kellner P, Muller M, Piegeler T, Eugster P, Booy C, Schlapfer M, Beck-Schimmer B. Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury. Anesth Analg. 2017 Jan;124(1):194-203. doi: 10.1213/ANE.0000000000001530.

Reference Type BACKGROUND
PMID: 27782948 (View on PubMed)

Other Identifiers

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SSiS

Identifier Type: -

Identifier Source: org_study_id

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