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SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival (SAVE-ICU)

Primary Purpose

Covid19, Hypoxic Respiratory Failure

Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Isoflurane Inhalant Product
Sevoflurane inhalant product
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring sedation, ICU, volatile anesthetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. ≥ 18 years of age;
  2. Mechanically ventilated and expected to remain mechanically ventilated at the end of the next day;
  3. Receiving IV sedation by infusion or bolus for ≤72 hours to facilitate mechanical ventilation. Transferred patients with escalating ventilation needs are eligible for recruitment within ≤72 hours of sedation commenced within the participating trial site that they were transferred to. Note: Intravenous sedation required to support mechanical ventilation includes use of one or more of the following agents: benzodiazepines, propofol, ketamine, barbiturates, alpha-2 agonist, opioids. Patients receiving intravenous opioids only i.e., fentanyl ≥ 50mcg/hour, hydromorphone ≥ 0.4mg/hour (or bolus q1h) for analgesia and sedation or agitation to assist mechanical ventilation are eligible for inclusion.
  4. a) Proven or suspected (under investigation) COVID-19, or b) COVID-19 negative patients who have a PaO2FiO2 ratio ≤300 measured with arterial blood gas at least once during the 12 hours prior to enrollment.

Exclusion Criteria:

  1. Contraindications to sedatives, such as propofol infusion syndrome or malignant hyperthermia;
  2. Known allergy to any of the ingredients or components of the investigational products; sevoflurane or isoflurane;
  3. Suspect or evidence of high intracranial pressure;
  4. Severe brain injury that is likely to lead to sustained very low conscious levels or vegetative state;
  5. Severe neuromuscular disorder for example amyotrophic lateral sclerosis, Gullian Barre Syndrome that are the primary cause of needing ICU admission and mechanical ventilation;
  6. One-lung ventilation or pneumonectomy;
  7. Ideal estimated tidal volume too low for delivery of inhaled agents. Target (6ml/kg) < 200ml;
  8. Use of inhaled prostacyclin which is contraindicated in the presence of a miniature vaporizer (i.e., Anesthesia Conserving Device). This agent has a high viscosity that leads to poor vaporization of the volatile agent. Note: Other inhaled pulmonary vasodilators such as nitric oxide can be safely administered in the presence of miniature vaporizers. Use of prostacyclin is permissible with an anesthesia machine and MADM;
  9. Known pregnancy
  10. Moribund patient not expected to survive >12 hours

Sites / Locations

  • University of Alberta HospitalRecruiting
  • London Health Sciences Centre - University HospitalRecruiting
  • London Health Sciences Centre - Victoria HospitalRecruiting
  • The Ottawa HospitalRecruiting
  • Sunnybrook Health Sciences CentreRecruiting
  • University Health Network - Toronto General HospitalRecruiting
  • University Health Network - Toronto Western HopsitalRecruiting
  • Centre Hospitalier de l'Université de MontréalRecruiting
  • McGill University Health Centre - Royal Victoria HospitalRecruiting
  • Hôpital Sacré-Coeur de MontréalRecruiting
  • Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)
  • Universite de SherbrookeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

No Intervention

Arm Label

Inhaled - volatile anesthetic

Standard Care

Non-randomized

Arm Description

The ICU patient will be randomized to either Isoflurane or Sevoflurane, whichever is available at the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.

The ICU patient will be randomized to standard of care, which is any IV sedation supplied by the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.

In this arm, ICU patients who cannot be randomized will receive inhaled or IV sedation as per available in their unit. This is done to try to obtain the maximum amount of information available from the patients present to our ICUs.

Outcomes

Primary Outcome Measures

Hospital Mortality
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant hospital mortality as compared to standard intravenous sedation regimen with a 10% difference between groups for 752 participants.
Ventilator-Free Days
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant ventilation outcomes after 30 days post enrollment, as compared to standard intravenous sedation regimen for 200 participants
ICU-Free Days
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant time spent in ICU, 30 days post enrollment, as compared to standard intravenous sedation regimen for 128 participants
Participant Quality of Life at 3 and 12 months after discharge
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant quality of life outcomes at 3 and 12 months post discharge as compared to standard intravenous sedation regimen for 144 participants. The EQ-5D questionnaire will be completed at both time points

Secondary Outcome Measures

Median Daily Oxygenation
To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment
Delirium and Coma Free Days
To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment
Adjunctive ARDS therapies
To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay
Hospital-Free Days
To evaluate the number of hospital-free days for participants, 60 days after enrollment
Disability
To evaluate participant disability at 3 and 12 months post discharge. The World Health Organization Disabiltity Assessment Score (WHODAS 2.0) will be completed at both timepoints. The scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items.

Full Information

First Posted
June 2, 2020
Last Updated
April 25, 2023
Sponsor
Sunnybrook Health Sciences Centre
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1. Study Identification

Unique Protocol Identification Number
NCT04415060
Brief Title
SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival
Acronym
SAVE-ICU
Official Title
SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival. Multicentre Open-label, Pragmatic, Randomized Controlled Trial and a Parallel Prospective (Non-randomized) Cohort Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2020 (Actual)
Primary Completion Date
June 15, 2024 (Anticipated)
Study Completion Date
June 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients suffering lung failure, possibly from COVID-19 or hypoxic lung failure, will need life-saving support from a breathing machine. Any patient needing this support requires drugs to keep them sleepy, or "sedated" to be comfortable on this machine. Sedation is made possible by using drugs given through a vein. Unfortunately, these drugs are in short supply worldwide due to the high number of COVID-19 patients needing these machines. Another way to provide sleep is by using gases that are breathed in. These are used every day in operating rooms to perform surgery. These gases, also called "inhaled agents" can also be used in intensive care units and may have several important benefits for patients and the hospital. Research shows they may reduce swelling in the lung and increase oxygen levels, which allows patients to recover faster and reduce the time spent on a breathing machine. In turn, this allows the breathing machine to be used again for the next sick patient. These drugs may also increase the number of patients who live through their illness. Inhaled agents are widely available and their use could dramatically lesson the pressure on limited drug supplies. This research is a study being carried out in a number of hospitals that will compare how well patients recover from these illnesses depending on which type of sedation drug they receive. The plan is to evaluate the number who survive, their time spent on a breathing machine and time in the hospital. This study may show immediate benefits and may provide a cost effective and practical solution to the current challenges caring for patients and the hospital space, equipment and drugs to the greatest benefit. Furthermore, the study will be investigating inflammatory profile and neuro-cognitive profiles in ventilated patients. Finally, this trial will be a team of experts in sedation drugs who care for patients with proven or suspected COVID-19 who need lifesaving treatments.
Detailed Description
Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study conducted in ICUs and ICU enabled environments caring in critically ill COVID-19 and non-COVID hypoxic respiratory failure patients. Participants will be mechanically ventilated and will be variably randomized, within 72 hours of start of sedation treatment, in a 1:1 ratio to either an intravenous or inhaled volatile-based sedation arm depending on availability of sedative drugs for both arms. Stratification will be done by: Age ≥ 65 years participating centre PaO2/FiO2 ratio of 150 Patients who cannot be randomized (due to technical or resource issues in some areas of the hospital) will be entered into the parallel prospective (non-randomized) cohort study and will receive intravenous or inhaled sedation as able in their designated unit. Sedation will be administered according to standard sedation practice and in keeping with current guidelines. Participants will be followed: daily in ICU until 30 days after enrollment, ICU discharge or death, whichever occurs first; at 30 days after last dose of drug administration by telephone or through the hospital healthcare database; at 60 days, 90 days, and 365 days after enrollment by telephone and/or through data linkages with a provincial or hospital or state healthcare database; Participants will have the option to participate in the neuro-cognitive and / or biomarker assessments

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Hypoxic Respiratory Failure
Keywords
sedation, ICU, volatile anesthetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
758 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Inhaled - volatile anesthetic
Arm Type
Experimental
Arm Description
The ICU patient will be randomized to either Isoflurane or Sevoflurane, whichever is available at the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.
Arm Title
Standard Care
Arm Type
No Intervention
Arm Description
The ICU patient will be randomized to standard of care, which is any IV sedation supplied by the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.
Arm Title
Non-randomized
Arm Type
No Intervention
Arm Description
In this arm, ICU patients who cannot be randomized will receive inhaled or IV sedation as per available in their unit. This is done to try to obtain the maximum amount of information available from the patients present to our ICUs.
Intervention Type
Drug
Intervention Name(s)
Isoflurane Inhalant Product
Intervention Description
Isoflurane will be administered using an inhalation device
Intervention Type
Drug
Intervention Name(s)
Sevoflurane inhalant product
Intervention Description
Sevoflurane will be administered using an inhalation device
Primary Outcome Measure Information:
Title
Hospital Mortality
Description
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant hospital mortality as compared to standard intravenous sedation regimen with a 10% difference between groups for 752 participants.
Time Frame
2 years
Title
Ventilator-Free Days
Description
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant ventilation outcomes after 30 days post enrollment, as compared to standard intravenous sedation regimen for 200 participants
Time Frame
30 days
Title
ICU-Free Days
Description
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant time spent in ICU, 30 days post enrollment, as compared to standard intravenous sedation regimen for 128 participants
Time Frame
30 days
Title
Participant Quality of Life at 3 and 12 months after discharge
Description
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant quality of life outcomes at 3 and 12 months post discharge as compared to standard intravenous sedation regimen for 144 participants. The EQ-5D questionnaire will be completed at both time points
Time Frame
365 days
Secondary Outcome Measure Information:
Title
Median Daily Oxygenation
Description
To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment
Time Frame
3 days
Title
Delirium and Coma Free Days
Description
To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment
Time Frame
14 days
Title
Adjunctive ARDS therapies
Description
To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay
Time Frame
30 days
Title
Hospital-Free Days
Description
To evaluate the number of hospital-free days for participants, 60 days after enrollment
Time Frame
60 days
Title
Disability
Description
To evaluate participant disability at 3 and 12 months post discharge. The World Health Organization Disabiltity Assessment Score (WHODAS 2.0) will be completed at both timepoints. The scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items.
Time Frame
365 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 18 years of age Mechanically ventilated and expected to remain mechanically ventilated at the end of the next day Receiving IV sedation by infusion or bolus for ≤72 hours to facilitate mechanical ventilation Transferred patients with escalating ventilation needs are eligible for recruitment within ≤72 hours of sedation commenced within the participating trial site that they were transferred to. Note: Intravenous sedation required to support mechanical ventilation includes use of one or more of the following agents: benzodiazepines, propofol, ketamine, barbiturates, alpha-2 agonist, opioids. Patients receiving intravenous opioids only i.e., fentanyl ≥ 50mcg/hour, hydromorphone ≥ 0.4mg/hour (or bolus q1h) for analgesia and sedation or agitation to assist mechanical ventilation are eligible for inclusion. 4. a) Proven or suspected (under investigation) COVID-19, or b) COVID-19 negative patients who have a PaO2FiO2 ratio ≤300 measured with arterial blood gas at least once during the 12 hours prior to enrollment. Exclusion Criteria: Contraindications to sedatives, such as propofol infusion syndrome or malignant hyperthermia; Known allergy to any of the ingredients or components of the investigational products; sevoflurane or isoflurane; Suspect or evidence of high intracranial pressure; Severe brain injury that is likely to lead to sustained very low conscious levels or vegetative state Severe neuromuscular disorder for example amyotrophic lateral sclerosis, Gullian Barre Syndrome that are the primary cause of needing ICU admission and mechanical ventilation One-lung ventilation or pneumonectomy; Ideal estimated tidal volume too low for delivery of inhaled agents. Target (6ml/kg) < 200ml; Use of inhaled prostacyclin which is contraindicated in the presence of a miniature vaporizer (i.e., Anesthesia Conserving Device). This agent has a high viscosity that leads to poor vaporization of the volatile agent. Note: Other inhaled pulmonary vasodilators such as nitric oxide can be safely administered in the presence of miniature vaporizers. Use of prostacyclin is permissible with an anesthesia machine and MADM; Known pregnancy Moribund patient not expected to survive >12 hours
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angela Jerath, MD
Phone
416.480.6100
Email
angela.jerath@sunnybrook.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Iman Hussain
Email
SAVE-ICU@sunnybrook.ca
Facility Information:
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadia Baig
Phone
780-492-3817
Email
Nadia.Baig@ahs.ca
First Name & Middle Initial & Last Name & Degree
Michael Jacka, MD
Facility Name
London Health Sciences Centre - University Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tracey Bentall
Phone
519-685-8500
Ext
32546
Email
TraceyC.Bentall@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Marat Slessarev, MD
Facility Name
London Health Sciences Centre - Victoria Hospital
City
London
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eileen Campbell
Phone
519-685-8500
Ext
55664
Email
Eileen.Campbell@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Marat Slessarav, MD
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Haines
Email
jhaines@toh.ca
First Name & Middle Initial & Last Name & Degree
Irene Watpool
Email
iwatpool@toh.ca
First Name & Middle Initial & Last Name & Degree
Johnathan Hooper, MD
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lilia Kaustov
Phone
416.480.6100
Email
Lilia.Kaustov@sunnybrook.ca
First Name & Middle Initial & Last Name & Degree
Angela Jerath, MD
Facility Name
University Health Network - Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hesham Abdelhady
Phone
416-340-4800
Ext
6056
Email
Hesham.Abdelhady@uhn.ca
First Name & Middle Initial & Last Name & Degree
Tina Romagnuolo
Phone
416-340-4800
Ext
6056
Email
Tina.Romagnuolo@uhn.ca
First Name & Middle Initial & Last Name & Degree
Ewan Goligher, MD
Facility Name
University Health Network - Toronto Western Hopsital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emad AlAzizi
Phone
416-603-5800
Ext
6237
Email
Emad.AlAzizi@uhnresearch.ca
First Name & Middle Initial & Last Name & Degree
Deborah Mancini
Phone
416-603-5800
Ext
6237
Email
Deborah.Mancini@uhnresearch.ca
First Name & Middle Initial & Last Name & Degree
Ian Randall, MD
Facility Name
Centre Hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 3E4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cindy Prie
Phone
514-890-8000
Ext
20065
Email
cindy.prie.chum@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Francois-Martin Carrier, MD
Facility Name
McGill University Health Centre - Royal Victoria Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josie Campisi
Phone
514-934-1934
Ext
65542
Email
josie.campisi@muhc.mcgill.ca
First Name & Middle Initial & Last Name & Degree
Roupen Hatzakorzian, MD
Facility Name
Hôpital Sacré-Coeur de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4J1C5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Virginie Williams
Phone
514-338-2222
Ext
3487
Email
virginie.williams.cnmtl@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Alexandros Cavayas, MD
Facility Name
Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Universite de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1K 2R1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elaine Carbonneau
Phone
819-346-1110
Ext
16208
Email
ecarbonneau.chus@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Marie-Pier Bouchard
Phone
819-346-1110
Ext
16208
Email
marie-pier.bouchard.ciussse-chus@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Frederick D'Aragon, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival

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