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Sevoflurane in COVID-19 ARDS (SevCov)

Primary Purpose

ARDS, Human, Coronavirus

Status
Completed
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Sevoflurane
Intravenous drug
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ARDS, Human focused on measuring COVID-19, ARDS

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • SARS-CoV-2 infection (positive testing) or computed tomography (CT) scan-suspected COVID-19 ARDS
  • Male and female patients, age 18 to 85 years
  • ICU patients with ARDS defined as PaO2/FiO2 < 200mmHg (=26.6kPa)
  • Time of intubation not longer than 24 hours
  • QTc Time (ECG) not longer than 470 ms ♂ (male)/ 480 ms ♀ (female)
  • Sedation and mechanical ventilation in ICU
  • Informed consent, signed by a representative or by an independent physician

Exclusion Criteria:

  • High dose systemic corticosteroids in the phase before hospitalization (> 10mg/d prednisone or equivalent dose)
  • Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, seizure, burn, neuromuscular disease)
  • Organ transplant
  • AIDS
  • Pregnancy and/or breastfeeding
  • Use of cytokine absorber

Sites / Locations

  • Kantonsspital Münsterlingen
  • Cantonal Hospital of St. Gallen
  • Stadtspital Triemli
  • University Hospital Zuirch

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sevoflurane Sedation

Intravenous

Arm Description

Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS

No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine

Outcomes

Primary Outcome Measures

Composite outcome of death rate (rate of patients that did not survive) and organ failure rate (rate of patients surviving with persistent organ dysfunction) at day 28
The effect of sevoflurane application on mortality (rate of patients that does not survive 28 days) and persistent organ dysfunction (rate of patients surviving with a persistent organ failure at day 28) will be assessed. Organ failures are defined as pulmonary failure (necessity of ventilation); cardiovascular failure (need of vasopressors), retail failure (need of renal replacement therapy)

Secondary Outcome Measures

Length of stay ICU
The effect of sevoflurane application on the length of stay at ICU will be determined.
Plasma Inflammatory markers
The impact of sevoflurane on the course of inflammatory markers will be evaluated (pro-calcitonin, PCT; c-reactive protein, CRP; interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1)
Length of stay at hospital
The effect of sevoflurane application on the length of stay at hospital will be determined.
Sex-related differences in complications
Sex-related differences in complications will be assessed

Full Information

First Posted
March 26, 2020
Last Updated
July 16, 2021
Sponsor
University of Zurich
Collaborators
Kantonsspital Münsterlingen, Triemli Hospital, Cantonal Hospital of St. Gallen
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1. Study Identification

Unique Protocol Identification Number
NCT04355962
Brief Title
Sevoflurane in COVID-19 ARDS (SevCov)
Official Title
Sevoflurane Sedation in COVID-19 ARDS Patients to Reduce Lung Injury: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
April 23, 2020 (Actual)
Primary Completion Date
June 25, 2021 (Actual)
Study Completion Date
July 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
Kantonsspital Münsterlingen, Triemli Hospital, Cantonal Hospital of St. Gallen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this trial is to study the effect of initial temporary sevoflurane sedation on mortality and persistent organ dysfunction (POD) in survivors at day 28 after ICU admission in the population of patients suffering from COVID-19 ARDS.
Detailed Description
The corona virus disease 19 (COVID-19) pandemic, caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), is spreading rapidly across Europe. While data from European centers are still missing, several publications from Chinese centers are available. Respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality, and may be caused or exacerbated by a 'cytokine storm syndrome'. Recent trials from our group demonstrated that the volatile anesthetic sevoflurane administered during ventilation of patients has anti-inflammatory properties. Moreover, in in vivo studies volatile anesthetics reduce the severity of ARDS compared to intravenous sedation, which has been confirmed in a clinical pilot trial. Attenuating ARDS and thereby improving oxygenation strongly decreases morbidity and mortality of patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ARDS, Human, Coronavirus
Keywords
COVID-19, ARDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
a randomized, controlled multi-center trial
Masking
ParticipantOutcomes Assessor
Masking Description
Patients will not be informed about their group assignments, technicians processing the samples will not have any access to the ICU or the patient chart (= double-blind trial). Due to the procedures involved in volatile versus intravenous sedation, group assignment cannot be entirely concealed for the study staff and ICU doctors/nurses involved with the procedure in the ICU (pragmatic limits of blinding).
Allocation
Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sevoflurane Sedation
Arm Type
Experimental
Arm Description
Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS
Arm Title
Intravenous
Arm Type
Active Comparator
Arm Description
No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Intervention Description
Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS
Intervention Type
Drug
Intervention Name(s)
Intravenous drug
Intervention Description
Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine
Primary Outcome Measure Information:
Title
Composite outcome of death rate (rate of patients that did not survive) and organ failure rate (rate of patients surviving with persistent organ dysfunction) at day 28
Description
The effect of sevoflurane application on mortality (rate of patients that does not survive 28 days) and persistent organ dysfunction (rate of patients surviving with a persistent organ failure at day 28) will be assessed. Organ failures are defined as pulmonary failure (necessity of ventilation); cardiovascular failure (need of vasopressors), retail failure (need of renal replacement therapy)
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Length of stay ICU
Description
The effect of sevoflurane application on the length of stay at ICU will be determined.
Time Frame
28 days
Title
Plasma Inflammatory markers
Description
The impact of sevoflurane on the course of inflammatory markers will be evaluated (pro-calcitonin, PCT; c-reactive protein, CRP; interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1)
Time Frame
8 days
Title
Length of stay at hospital
Description
The effect of sevoflurane application on the length of stay at hospital will be determined.
Time Frame
28 days
Title
Sex-related differences in complications
Description
Sex-related differences in complications will be assessed
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: SARS-CoV-2 infection (positive testing) or computed tomography (CT) scan-suspected COVID-19 ARDS Male and female patients, age 18 to 85 years ICU patients with ARDS defined as PaO2/FiO2 < 200mmHg (=26.6kPa) Time of intubation not longer than 24 hours QTc Time (ECG) not longer than 470 ms ♂ (male)/ 480 ms ♀ (female) Sedation and mechanical ventilation in ICU Informed consent, signed by a representative or by an independent physician Exclusion Criteria: High dose systemic corticosteroids in the phase before hospitalization (> 10mg/d prednisone or equivalent dose) Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, seizure, burn, neuromuscular disease) Organ transplant AIDS Pregnancy and/or breastfeeding Use of cytokine absorber
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beatrice Beck Schimmer, Prof
Organizational Affiliation
University of Zurich
Official's Role
Study Chair
Facility Information:
Facility Name
Kantonsspital Münsterlingen
City
Münsterlingen
ZIP/Postal Code
8596
Country
Switzerland
Facility Name
Cantonal Hospital of St. Gallen
City
Sankt Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Stadtspital Triemli
City
Zurich
ZIP/Postal Code
8063
Country
Switzerland
Facility Name
University Hospital Zuirch
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32091533
Citation
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
Results Reference
background
PubMed Identifier
32031570
Citation
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113.
Results Reference
background
PubMed Identifier
32123994
Citation
Xie J, Tong Z, Guan X, Du B, Qiu H, Slutsky AS. Critical care crisis and some recommendations during the COVID-19 epidemic in China. Intensive Care Med. 2020 May;46(5):837-840. doi: 10.1007/s00134-020-05979-7. Epub 2020 Mar 2. No abstract available.
Results Reference
background
PubMed Identifier
17312223
Citation
Suter D, Spahn DR, Blumenthal S, Reyes L, Booy C, Z'graggen BR, Beck-Schimmer B. The immunomodulatory effect of sevoflurane in endotoxin-injured alveolar epithelial cells. Anesth Analg. 2007 Mar;104(3):638-45. doi: 10.1213/01.ane.0000255046.06058.58.
Results Reference
background
PubMed Identifier
17898018
Citation
Yue T, Roth Z'graggen B, Blumenthal S, Neff SB, Reyes L, Booy C, Steurer M, Spahn DR, Neff TA, Schmid ER, Beck-Schimmer B. Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro. Eur Respir J. 2008 Jan;31(1):118-25. doi: 10.1183/09031936.00046307. Epub 2007 Sep 26.
Results Reference
background

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Sevoflurane in COVID-19 ARDS (SevCov)

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