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

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

Sponsors

Lead Sponsor: Sunnybrook Health Sciences Centre

Source 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.

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.

Overall Status Recruiting
Start Date 2020-06-15
Completion Date 2023-06-15
Primary Completion Date 2023-06-15
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Hospital Mortality 2 years
Ventilator-Free Days 30 days
ICU-Free Days 30 days
Participant Quality of Life at 3 and 12 months after discharge 365 days
Secondary Outcome
Measure Time Frame
Median Daily Oxygenation 3 days
Delirium and Coma Free Days 14 days
Adjunctive ARDS therapies 30 days
Hospital-Free Days 60 days
Disability 365 days
Cost Utility Analysis 365 days
Enrollment 752
Condition
Intervention

Intervention Type: Drug

Intervention Name: Isoflurane Inhalant Product

Description: Isoflurane will be administered using an inhalation device

Arm Group Label: Inhaled - volatile anesthetic

Intervention Type: Drug

Intervention Name: Sevoflurane inhalant product

Description: Sevoflurane will be administered using an inhalation device

Arm Group Label: Inhaled - volatile anesthetic

Eligibility

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Contact

Last Name: Angela Jerath, MD

Phone: 416.480.6100

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
University of Alberta Hospital | Edmonton, Alberta, T6G 2B7, Canada Recruiting Nadia Baig 780-492-3817 [email protected] Michael Jacka, MD Principal Investigator
London Health Sciences Centre - University Hospital | London, Ontario, N6A 5A5, Canada Recruiting Tracey Bentall 519-685-8500 32546 [email protected] Marat Slessarev, MD Principal Investigator
London Health Sciences Centre - Victoria Hospital | London, Ontario, Canada Recruiting Eileen Campbell 519-685-8500 55664 [email protected] Marat Slessarav, MD Principal Investigator
The Ottawa Hospital | Ottawa, Ontario, Canada Not yet recruiting Jessica Haines [email protected]
Sunnybrook Health Sciences Centre | Toronto, Ontario, M4N3M5, Canada Recruiting Lilia Kaustov 416.480.6100 [email protected] Angela Jerath, MD Principal Investigator
University Health Network - Toronto General Hospital | Toronto, Ontario, M5G 2C4, Canada Recruiting Hesham Abdelhady 416-340-4800 6056 [email protected] Ewan Goligher, MD Principal Investigator
University Health Network - Toronto Western Hopsital | Toronto, Ontario, M5T 2S8, Canada Recruiting Emad AlAzizi 416-603-5800 6237 [email protected] Ian Randall, MD Principal Investigator
Centre Hospitalier de l'Université de Montréal | Montréal, Quebec, H2X 3E4, Canada Recruiting Dounia Boumahni 514-890-8000 20065 [email protected] Francois-Martin Carrier, MD Principal Investigator
McGill University Health Centre - Royal Victoria Hospital | Montréal, Quebec, H4A 3J1, Canada Not yet recruiting Josie Campisi 514-934-1934 65542 [email protected] Roupen Hatzakorzian, MD Principal Investigator
Hôpital Sacré-Coeur de Montréal | Montréal, Quebec, H4J1C5, Canada Not yet recruiting Virginie Williams 514-338-2222 3487 [email protected] Alexandros Cavayas, MD Principal Investigator
Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ) | Québec, Quebec, G1V 4G5, Canada Recruiting Johane Lepage 418-656-8711 2681 Johane.Le[email protected] Etienne Couture, MD Principal Investigator
Universite de Sherbrooke | Sherbrooke, Quebec, J1K 2R1, Canada Recruiting Elaine Carbonneau 819-346-1110 16208 [email protected] Frederick D'Aragon, MD Principal Investigator
Location Countries

Canada

Verification Date

2021-04-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Inhaled - volatile anesthetic

Type: Experimental

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.

Label: Standard Care

Type: No Intervention

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.

Label: Non-randomized

Type: No Intervention

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.

Acronym SAVE-ICU
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study

Primary Purpose: Treatment

Masking: None (Open Label)

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