Shock, SepticPhase 2SSiSNCT03643367
Sevoflurane Sedation in Patients With Septic Shock
A Phase 2 study testing Sevoflurane in people with Shock, Septic, run by University of Zurich at 4 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Shock, Septic
- What is being tested?
- Sevoflurane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 4 sitesSwitzerland
- Study dates
- Jan 2026to Nov 2027
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 16Show fewer
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland4 sites
Kantonasspital Münsterlingen
Münsterlingen, 8596
Thomas Neff, PD Dr. med., 071 686 2108, thomas.neff@sec.stgag.ch
Stadtspital Triemli
Zurich, 8063
Patricia Fodor, KD Dr. med., +41444165202, patricia.fodor@triemli.zuerich.ch
University Hospital of Zurich
Zurich
Martin Schlaepfer, PD Dr med, +41442551111, martin.schlaepfer@usz.ch
Beatrice Beck Schimmer, Prof Dr med, beatrice.beck@usz.ch
Waidspital Zürich
Zurich
Christian Giambarba, Dr. med., +41443662021, christian.giambarba@waid.zuerich.ch
About this study
Official title: Sevoflurane Sedation: A Potentially Promising Immunomodulation in Patients With Septic Shock
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.
Read the 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.
- Conditions
- Shock, Septic
- Being tested
- Sevoflurane, Control Group
- Keywords
- Sepsis, Septic Shock, Sevoflurane Conditioning
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevofluraneDrug
Included patients, randomized in experimental group, intravenous sedation will be interrupted and followed by a 4 hour sedation with the volatile anesthetic sevoflurane.
Control GroupDrug
Also called Propofol
Included patients randomized in control group, intravenouse sedation is continued with propofol
| Study group | Role | What they receive |
|---|---|---|
| Sevoflurane Sedation | Experimental | Patients randomized into experimental group will be treated with sevoflurane during 4 hours Receives: Drug: Sevoflurane |
| Propofol Sedation | Active comparator | Patients randomized into Control Group will get continued intravenous sedation with propofol Receives: Drug: Control Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of interleukin-6 over time
To see if the interleukin-6 decreases under the influence of sevoflurane
Measured: 5 days
Secondary outcomes (6)
Pro-/anti-inflammatory mediators
effect on inflammatory/anti- inflammatory mediators
Measured: 5 days
Vasopressor support
Use of vasopressor support (norepinephrine, dobutamine, vasopressin) will be determined.
Measured: 5 days
Sequential organ failure score (SOFA Score)
Sepsis related organ failure score
Measured: 5 days
Richmond Agitation Sedation Scale
A scale to measure the agitation or sedation level of a patient
Measured: 5 days
Duration of mechanical ventilation
Time of mechanical ventilation
Measured: 28 days
Mortality
Mortality information in intensive care unit and on the ward
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study startJan 2026 (estimated)
- Primary completionFeb 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Shock, SepticStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 153 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Kantonsspital Münsterlingen, Triemli Hospital, Waid City Hospital, Zurich
- Responsible party
- Sponsor
- Investigators
- Martin Schlaepfer, PD, Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03643367
- Sponsor's protocol ID
- SSiS
- Acronym
- SSiS
- Status last verified
- Mar 2025
- First submitted
- 20 Jun 2017
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 17575094Lu 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.
PubMed 25960229Klag 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.
PubMed 27103972Rios-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.
PubMed 28380034Tschaikowsky 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.
PubMed 20646905Gordon 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.
PubMed 27483065Fleischmann 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.
PubMed 26414292Kellner 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.
PubMed 27782948
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sevoflurane Sedation: A Potentially Promising Immunomodulation in Patients With Septic Shock
- ClinicalTrials.gov ID
- NCT03643367
- Acronym / sponsor ID
- SSiS / SSiS
- Conditions
- Shock, Septic
- Keywords
- Sepsis, Septic Shock, Sevoflurane Conditioning
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 153 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Kantonsspital Münsterlingen, Triemli Hospital, Waid City Hospital, Zurich
- Study start
- Jan 2026 (estimated)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 22 Aug 2018 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Sevoflurane Sedation | Experimental | Drug: SevofluranePatients randomized into experimental group will be treated with sevoflurane during 4 hours |
| Propofol Sedation | Active comparator | Drug: Control GroupPatients randomized into Control Group will get continued intravenous sedation with propofol |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (16 listed)
- 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)
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 |
|---|---|---|
| SevofluraneIncluded patients, randomized in experimental group, intravenous sedation will be interrupted and followed by a 4 hour sedation with the volatile anesthetic sevoflurane. | Drug | Sevoflurane Sedation |
| Control GroupAlso: PropofolIncluded patients randomized in control group, intravenouse sedation is continued with propofol | Drug | Propofol Sedation |
Primary outcome
Concentration of interleukin-6 over time
Time frame: 5 days
To see if the interleukin-6 decreases under the influence of sevoflurane
6 secondary outcomes
Pro-/anti-inflammatory mediators
Time frame: 5 days
Vasopressor support
Time frame: 5 days
Sequential organ failure score (SOFA Score)
Time frame: 5 days
Richmond Agitation Sedation Scale
Time frame: 5 days
Duration of mechanical ventilation
Time frame: 28 days
Mortality
Time frame: 28 days
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 Apr 2025.
- Background: PubMed 17575094Tang 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.
- Background: PubMed 25960229Lu 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.
- Background: PubMed 27103972Klag 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.
- Background: PubMed 28380034Rios-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.
- Background: PubMed 20646905Tschaikowsky 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.
- Background: PubMed 27483065Gordon 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.
- Background: PubMed 26414292Fleischmann 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.
- Background: PubMed 27782948Kellner 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.
- Individual participant dataSharing planned: No
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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.
Martin Schlaepfer, PD principal investigator
University of Zurich
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sevoflurane in people with Shock, Septic, run by University of Zurich at 4 sites in Switzerland.
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 6 inclusion and 16 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 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Martin Schlaepfer, PD (+41 44 255 4690, martin.schlaepfer@usz.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of interleukin-6 over time (time frame: 5 days). 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 NCT03643367, which also lists 8 linked publications.
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 Apr 2025.