NCT04415060

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
800

participants targeted

Target at P50-P75 for phase_3 covid19

Timeline
13mo left

Started Jun 2020

Longer than P75 for phase_3 covid19

Geographic Reach
1 country

13 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Jun 2020Jun 2027

First Submitted

Initial submission to the registry

June 2, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 4, 2020

Completed
11 days until next milestone

Study Start

First participant enrolled

June 15, 2020

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2026

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 15, 2027

Expected
Last Updated

February 9, 2026

Status Verified

July 1, 2025

Enrollment Period

5.8 years

First QC Date

June 2, 2020

Last Update Submit

February 4, 2026

Conditions

Keywords

sedationICUvolatile anesthetics

Outcome Measures

Primary Outcomes (1)

  • 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 758 participants.

    365 days

Secondary Outcomes (8)

  • Ventilator-Free Days

    30 days

  • ICU-Free Days

    30 days

  • Participant Quality of Life at 3 months after discharge

    90 days

  • Delirium and Coma Free Days

    14 days

  • Median Daily Oxygenation

    3 days

  • +3 more secondary outcomes

Study Arms (3)

Inhaled - volatile anesthetic

EXPERIMENTAL

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 ProductDrug: Sevoflurane inhalant product

Standard Care

NO INTERVENTION

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.

Non-randomized

NO INTERVENTION

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.

Interventions

Isoflurane will be administered using an inhalation device

Inhaled - volatile anesthetic

Sevoflurane will be administered using an inhalation device

Inhaled - volatile anesthetic

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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.
  • Mechanically ventilated patients +/- extracorporeal membrane oxygenation (extracorporeal life) support with:
  • Proven or suspected (under investigation) COVID-19, or
  • 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.
  • Note: If arterial blood gas measurement is unavailable, the PaO2 can be imputed from the pulse oximetry measurement

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Grey Nuns Community Hospital

Edmonton, Alberta, T6L 5X8, Canada

Location

London Health Sciences Centre - University Hospital

London, Ontario, N6A 5A5, Canada

Location

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

University Health Network - Toronto Western Hopsital

Toronto, Ontario, M5T 2S8, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

McGill University Health Centre - Royal Victoria Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Hôpital Sacré-Coeur de Montréal

Montreal, Quebec, H4J1C5, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)

Québec, Quebec, G1V 4G5, Canada

Location

Universite de Sherbrooke

Sherbrooke, Quebec, J1K 2R1, Canada

Location

Related Publications (1)

  • Jerath A, Slessarev M, Martin C, D'Aragon F, Carrier FM, Senaratne J, Meggison H, Hooper J, Alexandros Cavayas Y, Goligher EC, Couture EJ, Randall I, Hatzakorzian R, Jacka M, Wiener-Kronish J, Xie Z, Pinto RL, Cuthbertson B; SAVE-ICU Investigators and the Canadian Critical Care Trials Group. Sedating with volatile anaesthetics for COVID-19 and non-COVID-19 acute hypoxaemic respiratory failure patients in ICU (SAVE-ICU): protocol for a randomised clinical trial. BMJ Open. 2025 Oct 13;15(10):e108441. doi: 10.1136/bmjopen-2025-108441.

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 2, 2020

First Posted

June 4, 2020

Study Start

June 15, 2020

Primary Completion

March 31, 2026

Study Completion (Estimated)

June 15, 2027

Last Updated

February 9, 2026

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations