Clinical trial NCT04355962: Sevoflurane in COVID-19 ARDS (SevCov)
Official title: Sevoflurane Sedation in COVID-19 ARDS Patients to Reduce Lung Injury: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ARDS, Human
Coronavirus
Keywords: COVID-19
ARDS
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Kantonsspital Münsterlingen
name: Triemli Hospital
name: Cantonal Hospital of St. Gallen
First posted: 2020-04-21
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: a randomized, controlled multi-center trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
measure: Length of stay ICU
timeFrame: 28 days
measure: Plasma Inflammatory markers
timeFrame: 8 days
measure: Length of stay at hospital
timeFrame: 28 days
measure: Sex-related differences in complications
timeFrame: 28 days
Other outcomes:
Locations:
city: Münsterlingen
country: Switzerland
facility: Kantonsspital Münsterlingen
city: Sankt Gallen
country: Switzerland
facility: Cantonal Hospital of St. Gallen
city: Zurich
country: Switzerland
facility: Stadtspital Triemli
city: Zurich
country: Switzerland
facility: University Hospital Zuirch
Study officials:
affiliation: University of Zurich
name: Beatrice Beck Schimmer, Prof
role: STUDY_CHAIR
References:
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. No abstract available.
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.
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. No abstract available.
citation: 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.
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. doi: 10.1183/09031936.00046307. Epub 2007 Sep 26.