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) (ISCA)

• ClinicalTrials.gov Identifier: NCT04383730
• Recruitment Status: Recruiting
• First Posted: May 12, 2020
• Last Update Posted: December 1, 2020
• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Hospital Clínico Universitario de Valencia; University Hospital Schleswig-Holstein; Groupe Hospitalier Pitie-Salpetriere
• Information provided by (Responsible Party): University Hospital, Clermont-Ferrand

Tracking Information

• First Submitted Date: May 8, 2020
• First Posted Date: May 12, 2020
• Last Update Posted Date: December 1, 2020
• Actual Study Start Date: June 26, 2020
• Estimated Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2020)

Number of days off the ventilator (VFD28, for ventilator-free days), taking into account death as a competing event [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 10, 2020)

• All-cause mortality [ Time Frame: Days 7, 14, and 28 after inclusion ]
  All-cause mortality
• Ventilator-free days [ Time Frame: 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 [ Time Frame: Day 28 after inclusion ]
  Number of days alive and not in the ICU from inclusion to day 28
• Duration of invasive mechanical ventilation [ Time Frame: Day 28 after inclusion ]
  Total duration of controlled mechanical ventilation to day 28
• Duration of controlled mechanical ventilation [ Time Frame: Day 28 after inclusion ]
  Total duration of controlled mechanical ventilation to day 28
• Physiological measures of lung function [ Time Frame: 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 [ Time Frame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion ]
  Partial pressure of arterial carbon dioxide (PaCO2)
• Physiological measures of lung function [ Time Frame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion ]
  Inspiratory plateau pressure
• Physiological measures of lung function [ Time Frame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion ]
  Driving pressure
• Physiological measures of lung function [ Time Frame: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion ]
  Mode of mechanical ventilation (assisted versus controlled)
• Physiological measures of lung function [ Time Frame: 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 [ Time Frame: Day 7 from inclusion ]
  Development of pneumothorax
• Development of complications [ Time Frame: Day 7 from inclusion ]
  Supraventricular tachycardia
• Development of complications [ Time Frame: Day 7 from inclusion ]
  New onset atrial fibrillation
• Duration of vasopressor use [ Time Frame: Day 28 after inclusion ]
  Total duration (in days) of vasopressor use
• Duration of renal replacement therapy [ Time Frame: Day 28 after inclusion ]
  Total duration (in days)of renal replacement therapy
• Duration (in days) of any adjuvant therapies [ Time Frame: 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 [ Time Frame: Day 28 from inclusion ]
  Number of days with continuous neuromuscular blockade
• Type of sedation practices [ Time Frame: Day 28 from inclusion ]
  Sedation drug(s) used (name(s))
• Duration of sedation practices [ Time Frame: Day 28 from inclusion ]
  Number of days with sedation
• Modalities of sedation practices [ Time Frame: Day 28 from inclusion ]
  If inhaled sedation, device used to deliver it

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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)
• 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)

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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Adult patients admitted in ICUrequiring invasive mechanical ventilation and suspected or confirmed COVID19

Condition

• Critically Illness
• Sedation
• Invasive Mechanical Ventilation
• Acute Respiratory Distress 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
• 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

Study Groups/Cohorts

• 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
  Intervention: Drug: Intravenous sedation
• 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.
  Intervention: Drug: Inhaled sedation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 10, 2020): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2020
• Estimated Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lise Laclautre; +33 4 73 754963; promo_interne_drci@chu-clermontferrand.fr

• Listed Location Countries: France, Germany, Spain, Switzerland, United States

Administrative Information

• NCT Number: NCT04383730
• Other Study ID Numbers: ISCA Study
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: University Hospital, Clermont-Ferrand
• Study Sponsor: University Hospital, Clermont-Ferrand

Collaborators

• Hospital Clínico Universitario de Valencia
• University Hospital Schleswig-Holstein
• Groupe Hospitalier Pitie-Salpetriere

Investigators

• Study Chair: Matthieu Jabaudon; University Hospital, Clermont-Ferrand

• PRS Account: University Hospital, Clermont-Ferrand
• Verification Date: July 2020