ARDS, Human, Coronavirus
Conditions
Keywords
COVID-19, ARDS
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.
Interventions
DRUGSevoflurane
Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS
DRUGIntravenous drug
Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine
Sponsors
Kantonsspital Münsterlingen
Triemli Hospital
Cantonal Hospital of St. Gallen
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
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).
Intervention model description
a randomized, controlled multi-center trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Length of stay at hospital | 28 days | The effect of sevoflurane application on the length of stay at hospital will be determined. |
| 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) |
| Sex-related differences in complications | 28 days | Sex-related differences in complications will be assessed |
Countries
Switzerland
Outcome results
None listed