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)

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Completed

CT.gov ID

NCT04383730

Collaborator

Hospital Clínico Universitario de Valencia (Other), University Hospital Schleswig-Holstein (Other), Groupe Hospitalier Pitie-Salpetriere (Other)

203

Enrollment

Locations

10.1

Actual Duration (Months)

16.9

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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:

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),
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),
report sedation practice patterns in critically ill patients during the COVID-19 pandemics (secondary objective).

Condition or Disease	Intervention/Treatment	Phase
Critically Illness Sedation Invasive Mechanical Ventilation Acute Respiratory Distress Syndrome	Drug: Intravenous sedation Drug: Inhaled sedation

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 :

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),
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),
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.

Study Design

Study Type:

Observational

Actual Enrollment :

203 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

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)

Actual Study Start Date :

Jun 26, 2020

Actual Primary Completion Date :

Apr 30, 2021

Actual Study Completion Date :

Apr 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Usual practice of intravenous sedation The choice of the intravenous sedative agent, including the type of and dosing of the agent, will be as per the treating clinicians at each center	Drug: Intravenous sedation Patients will be included retrospectively in the study by local investigators at each participating center. As this is a non-interventional study, sedation practices will be those currently used as standard practices in participating centers, including both intravenous and inhaled sedation practices
Usual practice of inhaled sedation The choice of the inhaled sedative agent, including the type of and dosing of the agent, will be as per the treating clinicians at each center.	Drug: Inhaled sedation Patients will be included retrospectively in the study by local investigators at each participating center. As this is a non-interventional study, sedation practices will be those currently used as standard practices in participating centers, including both intravenous and inhaled sedation practices

Arm

Intervention/Treatment

Usual practice of intravenous sedation

The choice of the intravenous sedative agent, including the type of and dosing of the agent, will be as per the treating clinicians at each center

Drug: Intravenous sedation

Patients will be included retrospectively in the study by local investigators at each participating center. As this is a non-interventional study, sedation practices will be those currently used as standard practices in participating centers, including both intravenous and inhaled sedation practices

Usual practice of inhaled sedation

The choice of the inhaled sedative agent, including the type of and dosing of the agent, will be as per the treating clinicians at each center.

Drug: Inhaled sedation

Outcome Measures

Primary Outcome Measures

Number of days off the ventilator (VFD28, for ventilator-free days), taking into account death as a competing event [Day 28 after inclusion]
Ventilator-free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after intubation, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 27 or died prior to day 28, VFDs will be zero. Patients transferred to another hospital or other health care facility will be followed to day 28 to assess this endpoint.

Secondary Outcome Measures

All-cause mortality [Days 7, 14, and 28 after inclusion]
All-cause mortality
Ventilator-free days [Days 7 and 14 after inclusion]
Ventilator-free days to days 7 and 14 are defined as the number of days from the time of initiating unassisted breathing to day 7 and 14 after intubation, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to days 7 and 14 If a patient returns to assisted breathing and subsequently achieves unassisted breathing to days 7 and 14 , VFDs will be counted from the end of the last period of assisted breathing to days 7 and 14. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 6 or 13 or died prior to days 7 and 14, respectively,VFDs to days 7 and 14 will be zero. Patients transferred to another hospital or other health care facility will be followed to days 7 and 14 to assess this endpoint.
ICU-free days [Day 28 after inclusion]
Number of days alive and not in the ICU from inclusion to day 28
Duration of invasive mechanical ventilation [Day 28 after inclusion]
Total duration of controlled mechanical ventilation to day 28
Duration of controlled mechanical ventilation [Day 28 after inclusion]
Total duration of controlled mechanical ventilation to day 28
Physiological measures of lung function [Days 1, 2, 3, 4, 5, 6, and 7 from inclusion]
Arterial hypoxemia, as assessed by the partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio (PaO2/FiO2)
Physiological measures of lung function [Days 1, 2, 3, 4, 5, 6, and 7 from inclusion]
Partial pressure of arterial carbon dioxide (PaCO2)
Physiological measures of lung function [Days 1, 2, 3, 4, 5, 6, and 7 from inclusion]
Inspiratory plateau pressure
Physiological measures of lung function [Days 1, 2, 3, 4, 5, 6, and 7 from inclusion]
Driving pressure
Physiological measures of lung function [Days 1, 2, 3, 4, 5, 6, and 7 from inclusion]
Mode of mechanical ventilation (assisted versus controlled)
Physiological measures of lung function [Days 1, 2, 3, 4, 5, 6, and 7 from inclusion]
If available, 100 ms occlusion pressure (P0.1), a marker of respiratory drive
Development of complications [Day 7 from inclusion]
Development of pneumothorax
Development of complications [Day 7 from inclusion]
Supraventricular tachycardia
Development of complications [Day 7 from inclusion]
New onset atrial fibrillation
Duration of vasopressor use [Day 28 after inclusion]
Total duration (in days) of vasopressor use
Duration of renal replacement therapy [Day 28 after inclusion]
Total duration (in days)of renal replacement therapy
Duration (in days) of any adjuvant therapies [Day 7 from inclusion]
Adjuvant therapies are defined as: prone position, recruitment maneuvers, inhaled nitric oxide, inhaled epoprostenol sodium, high frequency ventilation, ECMO, neuromuscular blockade
Duration of continuous neuromuscular blockade [Day 28 from inclusion]
Number of days with continuous neuromuscular blockade
Type of sedation practices [Day 28 from inclusion]
Sedation drug(s) used (name(s))
Duration of sedation practices [Day 28 from inclusion]
Number of days with sedation
Modalities of sedation practices [Day 28 from inclusion]
If inhaled sedation, device used to deliver it

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center, Inc.	Boston	Massachusetts	United States	02215
2	CHU	Brest		France
3	CHU	Clermont-Ferrand		France	63000
4	Centre Hospitalier	Dunkerque		France
5	Pitié-Salpêtrière Hospital - APHP	Paris		France	75013
6	CH Privé de la Loire	Saint-Étienne		France
7	Universitätsklinikum	Bochum		Germany
8	University Medical Center Schleswig-Holstein	Kiel		Germany
9	Universitätsklinikum	Oldenburg		Germany
10	Hospital Clínico Universitario de Valencia	Valencia		Spain
11	Cantonal Hospital	Münsterlingen		Switzerland
12	Universitätsspital	Zürich		Switzerland