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

Covid19 Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04415060
• Other study ID #: 2149
• Status: Recruiting
• Phase: Phase 3
• Start date: June 15, 2020
• Est. completion date: June 15, 2025

Study information

• Verified date: April 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: Angela Jerath, MD
• Phone: 416.480.6100
• Email: angela.jerath[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. Age ≥ 65 years

2. participating centre

3. 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 758
• Est. completion date: June 15, 2025
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Hypoxic Respiratory Failure
• Respiratory Insufficiency

Intervention

Drug:
• Isoflurane Inhalant Product
Isoflurane will be administered using an inhalation device
• Sevoflurane inhalant product
Sevoflurane will be administered using an inhalation device

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	Hôpital Sacré-Coeur de Montréal	Montréal	Quebec
Canada	McGill University Health Centre - Royal Victoria Hospital	Montréal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)	Québec	Quebec
Canada	Universite de Sherbrooke	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network - Toronto General Hospital	Toronto	Ontario
Canada	University Health Network - Toronto Western Hopsital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years
Primary	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	30 days
Primary	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	30 days
Primary	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	365 days
Secondary	Median Daily Oxygenation	To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment	3 days
Secondary	Delirium and Coma Free Days	To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment	14 days
Secondary	Adjunctive ARDS therapies	To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay	30 days
Secondary	Hospital-Free Days	To evaluate the number of hospital-free days for participants, 60 days after enrollment	60 days
Secondary	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.	365 days