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| Name | Class |
|---|---|
| Kantonsspital Münsterlingen | OTHER |
| Triemli Hospital | OTHER |
| Cantonal Hospital of St. Gallen | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sevoflurane Sedation | Experimental | Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS |
|
| Intravenous | Active Comparator | No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sevoflurane | Drug | Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Length of stay ICU | The effect of sevoflurane application on the length of stay at ICU will be determined. | 28 days |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Beatrice Beck Schimmer, Prof | University of Zurich | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kantonsspital Münsterlingen | Münsterlingen | 8596 | Switzerland | |||
| Cantonal Hospital of St. Gallen |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32091533 | Background | 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. | |
| 32031570 | Background |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D018352 | Coronavirus Infections |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D003333 | Coronaviridae Infections |
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| ID | Term |
|---|---|
| D000077149 | Sevoflurane |
| D007260 | Infusion Pumps |
| ID | Term |
|---|---|
| D008738 | Methyl Ethers |
| D004987 | Ethers |
| D009930 | Organic Chemicals |
| D006845 | Hydrocarbons, Fluorinated |
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a randomized, controlled multi-center trial
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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).
| Intravenous drug | Drug | Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine |
|
| 8 days |
| Length of stay at hospital | The effect of sevoflurane application on the length of stay at hospital will be determined. | 28 days |
| Sex-related differences in complications | Sex-related differences in complications will be assessed | 28 days |
| Sankt Gallen |
| 9007 |
| Switzerland |
| Stadtspital Triemli | Zurich | 8063 | Switzerland |
| University Hospital Zuirch | Zurich | 8091 | Switzerland |
| 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. |
| 32123994 | Background | 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. |
| 17312223 | Background | 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. |
| 17898018 | Background | 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. |
| 38536545 | Derived | Beck-Schimmer B, Schadde E, Pietsch U, Filipovic M, Dubendorfer-Dalbert S, Fodor P, Hubner T, Schuepbach R, Steiger P, David S, Kruger BD, Neff TA, Schlapfer M. Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial. Ann Intensive Care. 2024 Mar 27;14(1):41. doi: 10.1186/s13613-024-01276-4. |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D006846 |
| Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D004864 | Equipment and Supplies |
| D001187 | Artificial Organs |
| D013523 | Surgical Equipment |