Sevoflurane in COVID-19 ARDS (SevCov)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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ARDS, Human, Coronavirus

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Intravenous drug


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a randomized, controlled multi-center trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevoflurane Sedation<br>Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS | Drug: Sevoflurane<br>* Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS<br>|
| Active Comparator: Intravenous<br>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<br>* Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, ARDS