SAVE-ICU: SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival
Study Details
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. 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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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. |
Outcome Measures
Primary Outcome Measures
- Hospital Mortality [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.
- Ventilator-Free Days [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
- ICU-Free Days [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
- Participant Quality of Life at 3 and 12 months after discharge [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
- Median Daily Oxygenation [3 days]
To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment
- Delirium and Coma Free Days [14 days]
To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment
- Adjunctive ARDS therapies [30 days]
To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay
- Hospital-Free Days [60 days]
To evaluate the number of hospital-free days for participants, 60 days after enrollment
- Disability [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.
- Cost Utility Analysis [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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
≥ 18 years of age;
-
Mechanically ventilated and expected to remain mechanically ventilated at the end of the next day;
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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.
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- 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:
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Contraindications to sedatives, such as propofol infusion syndrome or malignant hyperthermia;
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Known allergy to any of the ingredients or components of the investigational products; sevoflurane or isoflurane;
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Suspect or evidence of high intracranial pressure;
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Severe brain injury that is likely to lead to sustained very low conscious levels or vegetative state;
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Severe neuromuscular disorder for example amyotrophic lateral sclerosis, Gullian Barre Syndrome that are the primary cause of needing ICU admission and mechanical ventilation;
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One-lung ventilation or pneumonectomy;
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Ideal estimated tidal volume too low for delivery of inhaled agents. Target (6ml/kg) < 200ml;
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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;
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Known pregnancy
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Moribund patient not expected to survive >12 hours
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
| 2 | London Health Sciences Centre - University Hospital | London | Ontario | Canada | N6A 5A5 |
| 3 | London Health Sciences Centre - Victoria Hospital | London | Ontario | Canada | |
| 4 | The Ottawa Hospital | Ottawa | Ontario | Canada | |
| 5 | Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | M4N3M5 |
| 6 | University Health Network - Toronto General Hospital | Toronto | Ontario | Canada | M5G 2C4 |
| 7 | University Health Network - Toronto Western Hopsital | Toronto | Ontario | Canada | M5T 2S8 |
| 8 | Centre Hospitalier de l'Université de Montréal | Montréal | Quebec | Canada | H2X 3E4 |
| 9 | McGill University Health Centre - Royal Victoria Hospital | Montréal | Quebec | Canada | H4A 3J1 |
| 10 | Hôpital Sacré-Coeur de Montréal | Montréal | Quebec | Canada | H4J1C5 |
| 11 | Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ) | Québec | Quebec | Canada | G1V 4G5 |
| 12 | Universite de Sherbrooke | Sherbrooke | Quebec | Canada | J1K 2R1 |
Sponsors and Collaborators
- Sunnybrook Health Sciences Centre
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2149