Sevoflurane in COVID-19 ARDS (SevCov)

Coronavirus Clinical Trial

Official title:

Sevoflurane Sedation in COVID-19 ARDS Patients to Reduce Lung Injury: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04355962
• Other study ID #: 2020-00719
• Status: Completed
• Phase: Phase 3
• Start date: April 23, 2020
• Est. completion date: July 16, 2021

Study information

• Verified date: July 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: July 16, 2021
• Est. primary completion date: June 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• ARDS, Human
• Coronavirus
• Respiratory Distress Syndrome, Adult

Intervention

Drug:
• Sevoflurane
Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS
• Intravenous drug
Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine

Locations

Country	Name	City	State
Switzerland	Kantonsspital Münsterlingen	Münsterlingen
Switzerland	Cantonal Hospital of St. Gallen	Sankt Gallen
Switzerland	Stadtspital Triemli	Zurich
Switzerland	University Hospital Zuirch	Zurich

Sponsors (4)

Lead Sponsor	Collaborator
University of Zurich	Cantonal Hospital of St. Gallen, Kantonsspital Münsterlingen, Triemli Hospital

Country where clinical trial is conducted

Switzerland, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. Epub 2007 Sep 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Length of stay ICU	The effect of sevoflurane application on the length of stay at ICU will be determined.	28 days
Secondary	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)	8 days
Secondary	Length of stay at hospital	The effect of sevoflurane application on the length of stay at hospital will be determined.	28 days
Secondary	Sex-related differences in complications	Sex-related differences in complications will be assessed	28 days