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

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ClinicalTrials.gov Identifier: NCT04415060
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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. 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.


Condition or disease Intervention/treatment Phase
Covid19 Hypoxic Respiratory Failure Drug: Isoflurane Inhalant Product Drug: Sevoflurane inhalant product Phase 3

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 patients.

Participants will be adults who are mechanically ventilated with proven or suspected COVID-19 disease or suffering from hypoxic lung failure. All centres will be required to randomize every available patient, as non-randomized participants can be entered into a parallel prospective cohort study to try to obtain the maximum amount of information available from the patients present to our ICUs.

There will be variable randomized ratios of 2:1 or 1:2 to either an intravenous based sedation arm or an inhaled volatile-based sedation arm. This randomization will be dependent on availability of sedative drugs for both arms. Patients who cannot be randomized (secondary to technical or resource issues in some areas of the hospital) 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 remain within their sedation arms until the primary care team decides to stop sedation. Participants will be followed daily throughout their ICU stay for 30 days after enrollment and then at death or hospital discharge (whichever occurs first).

Clinical information during ICU stay will be obtained from the patient chart, electronic medical records, or hospital databases. Participants will be followed using a provincial or hospital healthcare database to obtain survival, and hospital-free days at 60 days, 90 days and 365 days after enrollment.

After hospital discharge, participants will be followed up at; 3 and 12 months to assess quality of life using the EQ-5D; and to assess disability using the WHODAS 2.0.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 752 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 15, 2020
Estimated Primary Completion Date : June 15, 2023
Estimated Study Completion Date : June 15, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Inhaled - volatile anesthetic
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.
Drug: Isoflurane Inhalant Product
Isoflurane will be administered using an inhalation device

Drug: Sevoflurane inhalant product
Sevoflurane will be administered using an inhalation device

No Intervention: Standard Care
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.
No Intervention: Non-randomized
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.



Primary Outcome Measures :
  1. Hospital Mortality [ Time Frame: 2 years ]
    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.

  2. Ventilator-Free Days [ Time Frame: 30 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

  3. ICU-Free Days [ Time Frame: 30 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

  4. Participant Quality of Life at 3 and 12 months after discharge [ Time Frame: 365 days ]
    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 :
  1. Median Daily Oxygenation [ Time Frame: 3 days ]
    To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment

  2. Delirium and Coma Free Days [ Time Frame: 14 days ]
    To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment

  3. Adjunctive ARDS therapies [ Time Frame: 30 days ]
    To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay

  4. Hospital-Free Days [ Time Frame: 60 days ]
    To evaluate the number of hospital-free days for participants, 60 days after enrollment

  5. Disability [ Time Frame: 365 days ]
    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.

  6. Cost Utility Analysis [ Time Frame: 365 days ]
    Quality of Life (QALY) assessment to be calculated using the EQ-5D, comparison costs at 3 and 12 months post discharge, costs associated with hospital stay, devices and sedative costs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04415060


Contacts
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Contact: Angela Jerath, MD 416.480.6100 angela.jerath@sunnybrook.ca
Contact: Katie Sharp, MSc SAVE-ICU@sunnybrook.ca

Locations
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Canada, Alberta
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Nadia Baig    780-492-3817    Nadia.Baig@ahs.ca   
Principal Investigator: Michael Jacka, MD         
Canada, Ontario
London Health Sciences Centre - University Hospital Recruiting
London, Ontario, Canada, N6A 5A5
Contact: Tracey Bentall    519-685-8500 ext 32546    TraceyC.Bentall@lhsc.on.ca   
Principal Investigator: Marat Slessarev, MD         
London Health Sciences Centre - Victoria Hospital Recruiting
London, Ontario, Canada
Contact: Eileen Campbell    519-685-8500 ext 55664    Eileen.Campbell@lhsc.on.ca   
Principal Investigator: Marat Slessarav, MD         
The Ottawa Hospital Not yet recruiting
Ottawa, Ontario, Canada
Contact: Jessica Haines       jhaines@toh.ca   
Contact: Irene Watpool       iwatpool@toh.ca   
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N3M5
Contact: Lilia Kaustov    416.480.6100    Lilia.Kaustov@sunnybrook.ca   
Principal Investigator: Angela Jerath, MD         
University Health Network - Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Hesham Abdelhady    416-340-4800 ext 6056    Hesham.Abdelhady@uhn.ca   
Contact: Tina Romagnuolo    416-340-4800 ext 6056    Tina.Romagnuolo@uhn.ca   
Principal Investigator: Ewan Goligher, MD         
University Health Network - Toronto Western Hopsital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Emad AlAzizi    416-603-5800 ext 6237    Emad.AlAzizi@uhnresearch.ca   
Contact: Mary-Jane Salpeter    416-603-5800 ext 6237    MaryJane.Salpeter@uhn.ca   
Principal Investigator: Ian Randall, MD         
Canada, Quebec
Centre Hospitalier de l'Université de Montréal Recruiting
Montréal, Quebec, Canada, H2X 3E4
Contact: Dounia Boumahni    514-890-8000 ext 20065    dounia.boumahni.chum@ssss.gouv.qc.ca   
Principal Investigator: Francois-Martin Carrier, MD         
McGill University Health Centre - Royal Victoria Hospital Not yet recruiting
Montréal, Quebec, Canada, H4A 3J1
Contact: Josie Campisi    514-934-1934 ext 65542    josie.campisi@muhc.mcgill.ca   
Principal Investigator: Roupen Hatzakorzian, MD         
Hôpital Sacré-Coeur de Montréal Not yet recruiting
Montréal, Quebec, Canada, H4J1C5
Contact: Virginie Williams    514-338-2222 ext 3487    virginie.williams.cnmtl@ssss.gouv.qc.ca   
Principal Investigator: Alexandros Cavayas, MD         
Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ) Recruiting
Québec, Quebec, Canada, G1V 4G5
Contact: Johane Lepage    418-656-8711 ext 2681    Johane.Lepage@criucpq.ulaval.ca   
Principal Investigator: Etienne Couture, MD         
Universite de Sherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1K 2R1
Contact: Elaine Carbonneau    819-346-1110 ext 16208    ecarbonneau.chus@ssss.gouv.qc.ca   
Contact: Marie-Pier Bouchard    819-346-1110 ext 16208    marie-pier.bouchard.ciussse-chus@ssss.gouv.qc.ca   
Principal Investigator: Frederick D'Aragon, MD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04415060    
Other Study ID Numbers: 2149
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: April 14, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sunnybrook Health Sciences Centre:
sedation
ICU
volatile anesthetics
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Sevoflurane
Isoflurane
Platelet Aggregation Inhibitors
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs