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Sevoflurane Sedation in Patients With Septic Shock (SSiS)

Primary Purpose

Shock, Septic

Status
Not yet recruiting
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Sevoflurane
Control Group
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Shock, Septic focused on measuring Sepsis, Septic Shock, Sevoflurane Conditioning

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kantonasspital Münsterlingen
  • University Hospital of Zurich
  • Stadtspital Triemli
  • Waidspital Zürich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sevoflurane Sedation

Propofol Sedation

Arm Description

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

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

Outcomes

Primary Outcome Measures

Concentration of interleukin-6 over time
To see if the interleukin-6 decreases under the influence of sevoflurane

Secondary Outcome Measures

Pro-/anti-inflammatory mediators
effect on inflammatory/anti- inflammatory mediators
Vasopressor support
Use of vasopressor support (norepinephrine, dobutamine, vasopressin) will be determined.
Sequential organ failure score (SOFA Score)
Sepsis related organ failure score
Richmond Agitation Sedation Scale
A scale to measure the agitation or sedation level of a patient
Duration of mechanical ventilation
Time of mechanical ventilation
Mortality
Mortality information in intensive care unit and on the ward

Full Information

First Posted
June 20, 2017
Last Updated
May 22, 2022
Sponsor
University of Zurich
Collaborators
Kantonsspital Münsterlingen, Triemli Hospital, Waid City Hospital, Zurich
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1. Study Identification

Unique Protocol Identification Number
NCT03643367
Brief Title
Sevoflurane Sedation in Patients With Septic Shock
Acronym
SSiS
Official Title
Sevoflurane Sedation: A Potentially Promising Immunomodulation in Patients With Septic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2025 (Anticipated)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
Kantonsspital Münsterlingen, Triemli Hospital, Waid City Hospital, Zurich

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Shock, Septic
Keywords
Sepsis, Septic Shock, Sevoflurane Conditioning

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
ParticipantOutcomes Assessor
Masking Description
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)
Allocation
Randomized
Enrollment
153 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sevoflurane Sedation
Arm Type
Experimental
Arm Description
Patients randomized into experimental group will be treated with sevoflurane during 4 hours
Arm Title
Propofol Sedation
Arm Type
Active Comparator
Arm Description
Patients randomized into Control Group will get continued intravenous sedation with propofol
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Intervention Description
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
Intervention Name(s)
Control Group
Other Intervention Name(s)
Propofol
Intervention Description
Included patients randomized in control group, intravenouse sedation is continued with propofol
Primary Outcome Measure Information:
Title
Concentration of interleukin-6 over time
Description
To see if the interleukin-6 decreases under the influence of sevoflurane
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Pro-/anti-inflammatory mediators
Description
effect on inflammatory/anti- inflammatory mediators
Time Frame
5 days
Title
Vasopressor support
Description
Use of vasopressor support (norepinephrine, dobutamine, vasopressin) will be determined.
Time Frame
5 days
Title
Sequential organ failure score (SOFA Score)
Description
Sepsis related organ failure score
Time Frame
5 days
Title
Richmond Agitation Sedation Scale
Description
A scale to measure the agitation or sedation level of a patient
Time Frame
5 days
Title
Duration of mechanical ventilation
Description
Time of mechanical ventilation
Time Frame
28 days
Title
Mortality
Description
Mortality information in intensive care unit and on the ward
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Schlaepfer, PD
Phone
+41 44 255 4690
Email
martin.schlaepfer@usz.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Schläpfer, PD
Phone
+41 44 255 4690
Email
martin.schlaepfer@usz.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Schlaepfer, PD
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kantonasspital Münsterlingen
City
Münsterlingen
ZIP/Postal Code
8596
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Neff, PD Dr. med.
Phone
071 686 2108
Email
thomas.neff@sec.stgag.ch
Facility Name
University Hospital of Zurich
City
Zurich
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Schlaepfer, PD Dr med
Phone
+41442551111
Email
martin.schlaepfer@usz.ch
First Name & Middle Initial & Last Name & Degree
Beatrice Beck Schimmer, Prof Dr med
Email
beatrice.beck@usz.ch
First Name & Middle Initial & Last Name & Degree
Marco Maggiorini, Prof Dr med
Facility Name
Stadtspital Triemli
City
Zürich
ZIP/Postal Code
8063
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Fodor, KD Dr. med.
Phone
+41444165202
Email
patricia.fodor@triemli.zuerich.ch
Facility Name
Waidspital Zürich
City
Zürich
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Giambarba, Dr. med.
Phone
+41443662021
Email
christian.giambarba@waid.zuerich.ch

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17575094
Citation
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.
Results Reference
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PubMed Identifier
25960229
Citation
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.
Results Reference
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PubMed Identifier
27103972
Citation
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.
Results Reference
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PubMed Identifier
28380034
Citation
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.
Results Reference
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PubMed Identifier
20646905
Citation
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.
Results Reference
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PubMed Identifier
27483065
Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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PubMed Identifier
27782948
Citation
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.
Results Reference
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Sevoflurane Sedation in Patients With Septic Shock

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