Sevoflurane in COVID-19 ARDS (SevCov)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sevoflurane Sedation Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS |
Drug: Sevoflurane
Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS
|
| Active Comparator: Intravenous No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine |
Drug: Intravenous drug
Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine
|
Outcome Measures
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 [28 days]
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 [28 days]
The effect of sevoflurane application on the length of stay at ICU will be determined.
- Plasma Inflammatory markers [8 days]
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 [28 days]
The effect of sevoflurane application on the length of stay at hospital will be determined.
- Sex-related differences in complications [28 days]
Sex-related differences in complications will be assessed
Eligibility Criteria
Criteria
Inclusion Criteria:
-
SARS-CoV-2 infection (positive testing) or computed tomography (CT) scan-suspected COVID-19 ARDS
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Male and female patients, age 18 to 85 years
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ICU patients with ARDS defined as PaO2/FiO2 < 200mmHg (=26.6kPa)
-
Time of intubation not longer than 24 hours
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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)
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Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, seizure, burn, neuromuscular disease)
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Organ transplant
-
AIDS
-
Pregnancy and/or breastfeeding
-
Use of cytokine absorber
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kantonsspital Münsterlingen | Münsterlingen | Switzerland | 8596 | |
| 2 | Cantonal Hospital of St. Gallen | Sankt Gallen | Switzerland | 9007 | |
| 3 | Stadtspital Triemli | Zurich | Switzerland | 8063 | |
| 4 | University Hospital Zuirch | Zurich | Switzerland | 8091 |
Sponsors and Collaborators
- University of Zurich
- Kantonsspital Münsterlingen
- Triemli Hospital
- Cantonal Hospital of St. Gallen
Investigators
- Study Chair: Beatrice Beck Schimmer, Prof, University of Zurich
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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. Epub 2007 Sep 26.
- 2020-00719