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)

Acute Respiratory Distress Syndrome Clinical Trial

— ISCA  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04383730
• Other study ID #: ISCA Study
• Status: Completed
• Start date: June 26, 2020
• Est. completion date: April 30, 2021

Study information

• Verified date: August 2021
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: April 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Critically Illness
• Invasive Mechanical Ventilation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Sedation
• Syndrome

Intervention

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
• 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

Locations

Country	Name	City	State
France	CHU	Brest
France	CHU	Clermont-Ferrand
France	Centre Hospitalier	Dunkerque
France	Pitié-Salpêtrière Hospital - APHP	Paris
France	CH Privé de la Loire	Saint-Étienne
Germany	Universitätsklinikum	Bochum
Germany	University Medical Center Schleswig-Holstein	Kiel
Germany	Universitätsklinikum	Oldenburg
Spain	Hospital Clínico Universitario de Valencia	Valencia
Switzerland	Cantonal Hospital	Münsterlingen
Switzerland	Universitätsspital	Zürich
United States	Beth Israel Deaconess Medical Center, Inc.	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand	Groupe Hospitalier Pitie-Salpetriere, Hospital Clínico Universitario de Valencia, University Hospital Schleswig-Holstein

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of days off the ventilator (VFD28, for ventilator-free days), taking into account death as a competing event	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.	Day 28 after inclusion
Secondary	All-cause mortality	All-cause mortality	Days 7, 14, and 28 after inclusion
Secondary	Ventilator-free days	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.	Days 7 and 14 after inclusion
Secondary	ICU-free days	Number of days alive and not in the ICU from inclusion to day 28	Day 28 after inclusion
Secondary	Duration of invasive mechanical ventilation	Total duration of controlled mechanical ventilation to day 28	Day 28 after inclusion
Secondary	Duration of controlled mechanical ventilation	Total duration of controlled mechanical ventilation to day 28	Day 28 after inclusion
Secondary	Physiological measures of lung function	Arterial hypoxemia, as assessed by the partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio (PaO2/FiO2)	Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
Secondary	Physiological measures of lung function	Partial pressure of arterial carbon dioxide (PaCO2)	Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
Secondary	Physiological measures of lung function	Inspiratory plateau pressure	Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
Secondary	Physiological measures of lung function	Driving pressure	Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
Secondary	Physiological measures of lung function	Mode of mechanical ventilation (assisted versus controlled)	Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
Secondary	Physiological measures of lung function	If available, 100 ms occlusion pressure (P0.1), a marker of respiratory drive	Days 1, 2, 3, 4, 5, 6, and 7 from inclusion
Secondary	Development of complications	Development of pneumothorax	Day 7 from inclusion
Secondary	Development of complications	Supraventricular tachycardia	Day 7 from inclusion
Secondary	Development of complications	New onset atrial fibrillation	Day 7 from inclusion
Secondary	Duration of vasopressor use	Total duration (in days) of vasopressor use	Day 28 after inclusion
Secondary	Duration of renal replacement therapy	Total duration (in days)of renal replacement therapy	Day 28 after inclusion
Secondary	Duration (in days) of any adjuvant therapies	Adjuvant therapies are defined as: prone position, recruitment maneuvers, inhaled nitric oxide, inhaled epoprostenol sodium, high frequency ventilation, ECMO, neuromuscular blockade	Day 7 from inclusion
Secondary	Duration of continuous neuromuscular blockade	Number of days with continuous neuromuscular blockade	Day 28 from inclusion
Secondary	Type of sedation practices	Sedation drug(s) used (name(s))	Day 28 from inclusion
Secondary	Duration of sedation practices	Number of days with sedation	Day 28 from inclusion
Secondary	Modalities of sedation practices	If inhaled sedation, device used to deliver it	Day 28 from inclusion