Clinical trial NCT04383730: Inhaled Sedation in COVID-19-related Acute Respiratory Distress Syndrome (ISCA): an International Research Data Study in the Recent Context of Widespread Disease Resulting From the 2019 (SARS-CoV2) Coronavirus Pandemics (COVID-19)
Official title: Inhaled Sedation in COVID-19-related Acute Respiratory Distress Syndrome (ISCA): an International Research Data Study in the Recent Context of Widespread Disease Resulting From the 2019 (SARS-CoV2) Coronavirus Pandemics (COVID-19)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Critically Illness
Sedation
Invasive Mechanical Ventilation
Acute Respiratory Distress Syndrome
Keywords: Mechanical ventilation
Acute Respiratory Distress Syndrome
Inhaled sedation
Intravenous sedation
Covid-19
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Hospital Clínico Universitario de Valencia
name: University Hospital Schleswig-Holstein
name: Groupe Hospitalier Pitie-Salpetriere
First posted: 2020-05-12
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients admitted in ICUrequiring invasive mechanical ventilation and suspected or confirmed COVID19

Brief summary: The authors hypothesized that inhaled sedation, either with isoflurane or sevoflurane, might be associated with improved clinical outcomes in patients with COVID-19-related ARDS, compared to intravenous sedation.

The authors therefore designed the "Inhaled Sedation for COVID-19-related ARDS" (ISCA) non-interventional, observational, multicenter study of data collected from the patients' medical records in order to:

1. assess the efficacy of inhaled sedation in improving a composite outcome of mortality and time off the ventilator at 28 days in patients with COVID-19-related ARDS, in comparison to a control group receiving intravenous sedation (primary objective),
2. investigate the effects of inhaled sedation, compared to intravenous sedation, on lung function as assessed by gas exchange and physiologic measures in patients with COVID-19-related ARDS (secondary objective),
3. report sedation practice patterns in critically ill patients during the COVID-19 pandemics (secondary objective).

Detailed description: The acute respiratory distress syndrome (ARDS) is the most severe and lethal complication of COVID-19, and healthcare resource utilizations are currently being heavily challenged in most countries worldwide, with a high risk that some intensive care resources, such as the number of ventilators to allow management all patients, may be insufficient to face the current surge in ARDS cases. There is, therefore, an urgent need to evaluate candidate therapies that may impact clinical outcomes in patients with COVID-19-related ARDS and potentially be relevant to current public health issues, in accordance with the international efforts by the World Health Organization (WHO) (Global research on coronavirus disease) and most international public health organizations. Beyond the current efforts to find specific antiviral therapies or vaccines, improving supportive care and treatment options for patients with COVID-19-related ARDS, in accordance with up-to-date guidelines on the management of critically ill patients with COVID-19 (Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019; The Australian and New Zealand Intensive Care Society (ANZICS) COVID-19 Guidelines; Recommandations d'experts SRLF-SFAR-SFMU-GFRUP-SPILF sur la prise en charge en réanimation des patients en période d'épidémie à SARS-CoV2), is of major importance.

Indeed, given the number of intensive care unit (ICU) patients for whom the question of sedation applies during the current COVID-19 outbreak, any sedation practice that would be associated with improved clinical outcomes could have significant economic and public health implications. In this perspective, the rationale supporting inhaled sedation with halogenated agents (such as isoflurane or sevoflurane) as a way to improve lung function, to decrease the inflammatory response, and to possibly improve patient outcome is strong.

The authors hypothesized that inhaled sedation, either with isoflurane or sevoflurane, might be associated with improved clinical outcomes in patients with COVID-19-related ARDS, compared to intravenous sedation. The authors, therefore, designed the "Inhaled Sedation for COVID-19-related ARDS" (ISCA) non-interventional, observational, multicenter study of data collected from the patients' medical records in order to :

1. assess the efficacy of inhaled sedation in improving a composite outcome of mortality and time off the ventilator at 28 days in patients with COVID-19-related ARDS, in comparison to a control group receiving intravenous sedation (primary objective),
2. investigate the effects of inhaled sedation, compared to intravenous sedation, on lung function as assessed by gas exchange and physiologic measures in patients with COVID-19-related ARDS (secondary objective),
3. report sedation practice patterns in critically ill patients during the COVID-19 pandemics (secondary objective).

This study will be performed in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement.

Eligibility criteria: Inclusion Criteria:

* Adult patients (18 years old),
* Admitted to a participating ICU (or any other ICU-like setting that may be deployed as a result of the COVID-19 pandemics, such as in the operating room, post-anesthesia care unit, step-down unit or any COVID-19-specific unit set in response to the pandemics in a participating center),
* Requiring invasive mechanical ventilation,
* With suspected or confirmed COVID-19 on day 0.

Exclusion Criteria:

* None

Primary outcomes:
measure: Number of days off the ventilator (VFD28, for ventilator-free days), taking into account death as a competing event
timeFrame: Day 28 after inclusion
Secondary outcomes:
measure: All-cause mortality
timeFrame: Days 7, 14, and 28 after inclusion
measure: Ventilator-free days
timeFrame: Days 7 and 14 after inclusion
measure: ICU-free days
timeFrame: Day 28 after inclusion
measure: Duration of invasive mechanical ventilation
timeFrame: Day 28 after inclusion
measure: Duration of controlled mechanical ventilation
timeFrame: Day 28 after inclusion
measure: Physiological measures of lung function
timeFrame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
measure: Physiological measures of lung function
timeFrame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
measure: Physiological measures of lung function
timeFrame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
measure: Physiological measures of lung function
timeFrame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
measure: Physiological measures of lung function
timeFrame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
measure: Physiological measures of lung function
timeFrame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
measure: Development of complications
timeFrame: Day 7 from inclusion
measure: Development of complications
timeFrame: Day 7 from inclusion
measure: Development of complications
timeFrame: Day 7 from inclusion
measure: Duration of vasopressor use
timeFrame: Day 28 after inclusion
measure: Duration of renal replacement therapy
timeFrame: Day 28 after inclusion
measure: Duration (in days) of any adjuvant therapies
timeFrame: Day 7 from inclusion
measure: Duration of continuous neuromuscular blockade
timeFrame: Day 28 from inclusion
measure: Type of sedation practices
timeFrame: Day 28 from inclusion
measure: Duration of sedation practices
timeFrame: Day 28 from inclusion
measure: Modalities of sedation practices
timeFrame: Day 28 from inclusion
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center, Inc.
state: Massachusetts
city: Brest
country: France
facility: CHU
city: Clermont-Ferrand
country: France
facility: CHU
city: Dunkerque
country: France
facility: Centre Hospitalier
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital - APHP
city: Saint-Étienne
country: France
facility: CH Privé de la Loire
city: Bochum
country: Germany
facility: Universitätsklinikum
city: Kiel
country: Germany
facility: University Medical Center Schleswig-Holstein
city: Oldenburg
country: Germany
facility: Universitätsklinikum
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Münsterlingen
country: Switzerland
facility: Cantonal Hospital
city: Zürich
country: Switzerland
facility: Universitätsspital
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Matthieu Jabaudon
role: STUDY_CHAIR
References:
citation: Blondonnet R, Quinson A, Lambert C, Audard J, Godet T, Zhai R, Pereira B, Futier E, Bazin JE, Constantin JM, Jabaudon M. Use of volatile agents for sedation in the intensive care unit: A national survey in France. PLoS One. 2021 Apr 15;16(4):e0249889. doi: 10.1371/journal.pone.0249889. eCollection 2021.