Sevoflurane in COVID-19 ARDS (SevCov)

Phase 3

Completed

• Conditions: ARDS, Human; Coronavirus
• Interventions: Drug: Sevoflurane; Drug: Intravenous drug

• Registration Number: NCT04355962
• Lead Sponsor: University of Zurich

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.

Study Timeline

• Study First Submitted: 2020-03-26
• Study First Submitted QC: 2020-04-19
• Study First Posted: 2020-04-21
• Study Start: 2020-04-23
• Primary Completion: 2021-06-25
• Status Verified: 2021-07
• Study Completion: 2021-07-16
• Last Update Submitted: 2021-07-16
• Last Update Posted: 2021-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sevoflurane Sedation	Sevoflurane	Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS
Intravenous	Intravenous drug	No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Length of stay ICU	28 days	The effect of sevoflurane application on the length of stay at ICU will be determined.
Sex-related differences in complications	28 days	Sex-related differences in complications will be assessed
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.

Trial Locations

Locations (4)

Kantonsspital Münsterlingen; 🇨🇭 Münsterlingen, Switzerland

University Hospital Zuirch; 🇨🇭 Zurich, Switzerland

Stadtspital Triemli; 🇨🇭 Zurich, Switzerland

Cantonal Hospital of St. Gallen; 🇨🇭 Sankt Gallen, Switzerland