Respiratory FailureVol-ECMONCT05680545
Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane Oxygenation
A study testing Sevoflurane vaporized in ECMO machines in people with Respiratory Failure, run by University Health Network, Toronto.
Trial summary
The goal of this study is to design a pilot trial evaluating the safety, feasibility, pharmacokinetic modeling, and physiological effects of a volatile anesthetic, sevoflurane, directly administered in extracorporeal membrane oxygenation machines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure
- What is being tested?
- Sevoflurane vaporized in ECMO machines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2025to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients expected to be on VV ECMO support for a time frame of more than 24 hours and receiving a sevoflurane-based sedation protocol.
Who cannot join
- lack of informed consent for participation
- pregnancy
- serum bilirubin > 150 μmol/L
- ongoing massive blood transfusion requirement (> 50% blood volume transfused in the previous 8 hours)
- therapeutic plasma exchange and/or renal replacement therapy in the preceding 24 hours
- expected death or withdrawal of life support in the next 48 hours.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Eddy Fan, MD contact
About this study
Official title: Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane
The goal of this study is to design a pilot trial evaluating the safety, feasibility, pharmacokinetic modeling, and physiological effects of a volatile anesthetic, sevoflurane, directly administered in extracorporeal membrane oxygenation machines.
Read the detailed description
Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving therapy for catastrophic respiratory failure, including severe COVID-19. Optimal drug dosing in critically ill patients is challenging due to concomitant organ dysfunction, and with the addition of ECMO, the level of complexity significantly increases.
ECMO PK interactions with intravenous (IV) sedatives are complex and therapeutic failures are often encountered, highlighting the need for alternative sedation strategies. To overcome these limitations, volatile anesthetics are a potential solution for sedation and analgesia. Nevertheless, their use has been limited during ECMO support due to the low respiratory volumes associated with the lung-protective strategies, and the concerns of bioavailability given the compromised native lung function. The overarching aim of this project is to evaluate a strategy to mitigate the influence of ECMO on sedatives pharmacokinetics, using volatile anesthetics directly vaporized into ECMO oxygenators.
The study will consist of two phases: the ex-vivo trial an the in-vivo trial. For the ex-vivo trial, two ECMO circuits primed with Ringer's lactate will be used to design the dosing recommendations for the feasibility trial. Vaporized sevoflurane will be delivered directly into the membrane oxygenator with the ECMO gas and evacuated through the wall suction. Sevoflurane concentrations will be monitored with an infrared multi-gas analyzer sensor at the ECMO gas outlet. The test will be performed with different sweep flows and sevoflurane concentrations. Sevoflurane concentrations will be measured in the fluid to design a dosing model to conduct the in-vivo trial.
The in-vivo trial will be a prospective, single-center, open-label, pilot feasibility/PK study of 10 patients receiving venovenous ECMO (VV ECMO) in the Medical-Surgical Intensive Care Unit (MSICU) at the Toronto General Hospital. Following informed consent, these patients will be enrolled and managed with sevoflurane-based anesthesia directly delivered into the ECMO machine. During their ECMO run, samples will be taken and sevoflurane concentrations analyzed with headspace gas chromatography and mass spectrometry. Sedation scales, surrogates of respiratory dynamics and effort, and biotrauma inflammatory cytokines levels will be obtained at the same time.
- Conditions
- Respiratory Failure
- Being tested
- Sevoflurane vaporized in ECMO machines
- Keywords
- Extracorporeal membrane oxygenation, Volatile anesthetics, Sedation
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sevoflurane vaporized in ECMO machinesOther
Sevoflurane will be directly vaporized into the ECMO machine through the sweep gas.
| Study group | Role | What they receive |
|---|---|---|
| Sevoflurane vaporized in ECMO machines | Experimental | Patients' sedation will be managed with sevoflurane-based anesthesia directly vaporized into the ECMO machine. Receives: Other: Sevoflurane vaporized in ECMO machines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sevoflurane plasma concentrations
Plasma concentrations of sevoflurane will be measured with gas chromatography and mass spectrometry
Measured: 7 days
Secondary outcomes (4)
Percentage of sevoflurane in ECMO exhausted gas
The volume/volume percentage of sevoflurane will be measured with an infrared multi-gas analyzer sensor at the sweep gas outlet
Measured: 7 days
Respiratory dynamics and respiratory effort
Driving pressure, occlusion pressure, and P0.1 pressures will be measured with the patients mechanical ventilator daily
Measured: 7 days
Plasma levels of ventilator-induced lung injury biomarkers
As a surrogate for ventilator-induced lung injury, plasma levels of interleukins 6 and 8, and necrosis tumor factor will be measured daily
Measured: 7 days
Required doses of sedative adjuvants
The doses of other sedatives and analgesics, including opioids, antipsychotics, benzodiazepines, ketamine and propofol will be recorded
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2023
- Study start1 Jul 2025 (estimated)
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Respiratory FailureStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, single-center, open-label, pharmacokinetic study
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Responsible party
- Principal investigator, Diana Morales Castro, University Health Network, Toronto
- Investigators
- Diana Morales Castro, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05680545
- Sponsor's protocol ID
- 22-6007
- Other IDs
- 2022-2746
- Acronym
- Vol-ECMO
- Status last verified
- Dec 2024
- First submitted
- 16 Dec 2022
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
McMullan V, Alston RP, Tyrrell J. Volatile anaesthesia during cardiopulmonary bypass. Perfusion. 2015 Jan;30(1):6-16. doi: 10.1177/0267659114531314. Epub 2014 Apr 14.
PubMed 24732827LaGrew JE, Olsen KR, Frantz A. Volatile anaesthetic for treatment of respiratory failure from status asthmaticus requiring extracorporeal membrane oxygenation. BMJ Case Rep. 2020 Jan 15;13(1):e231507. doi: 10.1136/bcr-2019-231507.
PubMed 31948977Fan E, Gattinoni L, Combes A, Schmidt M, Peek G, Brodie D, Muller T, Morelli A, Ranieri VM, Pesenti A, Brochard L, Hodgson C, Van Kiersbilck C, Roch A, Quintel M, Papazian L. Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts. Intensive Care Med. 2016 May;42(5):712-724. doi: 10.1007/s00134-016-4314-7. Epub 2016 Mar 23.
PubMed 27007108Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K. Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients. Expert Opin Drug Metab Toxicol. 2019 Feb;15(2):103-112. doi: 10.1080/17425255.2019.1563596. Epub 2019 Jan 3.
PubMed 30582435Shekar K, Roberts JA, Mcdonald CI, Fisquet S, Barnett AG, Mullany DV, Ghassabian S, Wallis SC, Fung YL, Smith MT, Fraser JF. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012 Oct 15;16(5):R194. doi: 10.1186/cc11679.
PubMed 23068416Shekar K, Roberts JA, Mullany DV, Corley A, Fisquet S, Bull TN, Barnett AG, Fraser JF. Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure. Anaesth Intensive Care. 2012 Jul;40(4):648-55. doi: 10.1177/0310057X1204000411.
PubMed 22813493Bellgardt M, Ozcelik D, Breuer-Kaiser AFC, Steinfort C, Breuer TGK, Weber TP, Herzog-Niescery J. Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome. World J Crit Care Med. 2021 Nov 9;10(6):323-333. doi: 10.5492/wjccm.v10.i6.323. eCollection 2021 Nov 9.
PubMed 34888158Rand A, Zahn PK, Schildhauer TA, Waydhas C, Hamsen U. Inhalative sedation with small tidal volumes under venovenous ECMO. J Artif Organs. 2018 Jun;21(2):201-205. doi: 10.1007/s10047-018-1030-9. Epub 2018 Mar 5.
PubMed 29508167Ferrando C, Aguilar G, Piqueras L, Soro M, Moreno J, Belda FJ. Sevoflurane, but not propofol, reduces the lung inflammatory response and improves oxygenation in an acute respiratory distress syndrome model: a randomised laboratory study. Eur J Anaesthesiol. 2013 Aug;30(8):455-63. doi: 10.1097/EJA.0b013e32835f0aa5.
PubMed 23545542
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Volatile Anesthetic Pharmacokinetics During Extracorporeal Membrane
- ClinicalTrials.gov ID
- NCT05680545
- Acronym / sponsor ID
- Vol-ECMO / 22-6007
- Conditions
- Respiratory Failure
- Keywords
- Extracorporeal membrane oxygenation, Volatile anesthetics, Sedation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Study start
- 1 Jul 2025 (estimated)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 11 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to design a pilot trial evaluating the safety, feasibility, pharmacokinetic modeling, and physiological effects of a volatile anesthetic, sevoflurane, directly administered in extracorporeal membrane oxygenation machines.
Detailed description
Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving therapy for catastrophic respiratory failure, including severe COVID-19. Optimal drug dosing in critically ill patients is challenging due to concomitant organ dysfunction, and with the addition of ECMO, the level of complexity significantly increases.
ECMO PK interactions with intravenous (IV) sedatives are complex and therapeutic failures are often encountered, highlighting the need for alternative sedation strategies. To overcome these limitations, volatile anesthetics are a potential solution for sedation and analgesia. Nevertheless, their use has been limited during ECMO support due to the low respiratory volumes associated with the lung-protective strategies, and the concerns of bioavailability given the compromised native lung function. The overarching aim of this project is to evaluate a strategy to mitigate the influence of ECMO on sedatives pharmacokinetics, using volatile anesthetics directly vaporized into ECMO oxygenators.
The study will consist of two phases: the ex-vivo trial an the in-vivo trial. For the ex-vivo trial, two ECMO circuits primed with Ringer's lactate will be used to design the dosing recommendations for the feasibility trial. Vaporized sevoflurane will be delivered directly into the membrane oxygenator with the ECMO gas and evacuated through the wall suction. Sevoflurane concentrations will be monitored with an infrared multi-gas analyzer sensor at the ECMO gas outlet. The test will be performed with different sweep flows and sevoflurane concentrations. Sevoflurane concentrations will be measured in the fluid to design a dosing model to conduct the in-vivo trial.
The in-vivo trial will be a prospective, single-center, open-label, pilot feasibility/PK study of 10 patients receiving venovenous ECMO (VV ECMO) in the Medical-Surgical Intensive Care Unit (MSICU) at the Toronto General Hospital. Following informed consent, these patients will be enrolled and managed with sevoflurane-based anesthesia directly delivered into the ECMO machine. During their ECMO run, samples will be taken and sevoflurane concentrations analyzed with headspace gas chromatography and mass spectrometry. Sedation scales, surrogates of respiratory dynamics and effort, and biotrauma inflammatory cytokines levels will be obtained at the same time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, single-center, open-label, pharmacokinetic study
| Arm | Type | Receives |
|---|---|---|
| Sevoflurane vaporized in ECMO machines | Experimental | Other: Sevoflurane vaporized in ECMO machinesPatients' sedation will be managed with sevoflurane-based anesthesia directly vaporized into the ECMO machine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adult patients expected to be on VV ECMO support for a time frame of more than 24 hours and receiving a sevoflurane-based sedation protocol.
Key exclusion criteria (6 listed)
- lack of informed consent for participation
- pregnancy
- serum bilirubin > 150 μmol/L
- ongoing massive blood transfusion requirement (> 50% blood volume transfused in the previous 8 hours)
- therapeutic plasma exchange and/or renal replacement therapy in the preceding 24 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sevoflurane vaporized in ECMO machinesSevoflurane will be directly vaporized into the ECMO machine through the sweep gas. | Other | Sevoflurane vaporized in ECMO machines |
Primary outcome
Sevoflurane plasma concentrations
Time frame: 7 days
Plasma concentrations of sevoflurane will be measured with gas chromatography and mass spectrometry
4 secondary outcomes
Percentage of sevoflurane in ECMO exhausted gas
Time frame: 7 days
Respiratory dynamics and respiratory effort
Time frame: 7 days
Plasma levels of ventilator-induced lung injury biomarkers
Time frame: 7 days
Required doses of sedative adjuvants
Time frame: 7 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Background: PubMed 24732827McMullan V, Alston RP, Tyrrell J. Volatile anaesthesia during cardiopulmonary bypass. Perfusion. 2015 Jan;30(1):6-16. doi: 10.1177/0267659114531314. Epub 2014 Apr 14.
- Background: PubMed 31948977LaGrew JE, Olsen KR, Frantz A. Volatile anaesthetic for treatment of respiratory failure from status asthmaticus requiring extracorporeal membrane oxygenation. BMJ Case Rep. 2020 Jan 15;13(1):e231507. doi: 10.1136/bcr-2019-231507.
- Background: PubMed 27007108Fan E, Gattinoni L, Combes A, Schmidt M, Peek G, Brodie D, Muller T, Morelli A, Ranieri VM, Pesenti A, Brochard L, Hodgson C, Van Kiersbilck C, Roch A, Quintel M, Papazian L. Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts. Intensive Care Med. 2016 May;42(5):712-724. doi: 10.1007/s00134-016-4314-7. Epub 2016 Mar 23.
- Background: PubMed 30582435Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K. Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients. Expert Opin Drug Metab Toxicol. 2019 Feb;15(2):103-112. doi: 10.1080/17425255.2019.1563596. Epub 2019 Jan 3.
- Background: PubMed 23068416Shekar K, Roberts JA, Mcdonald CI, Fisquet S, Barnett AG, Mullany DV, Ghassabian S, Wallis SC, Fung YL, Smith MT, Fraser JF. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012 Oct 15;16(5):R194. doi: 10.1186/cc11679.
- Background: PubMed 22813493Shekar K, Roberts JA, Mullany DV, Corley A, Fisquet S, Bull TN, Barnett AG, Fraser JF. Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure. Anaesth Intensive Care. 2012 Jul;40(4):648-55. doi: 10.1177/0310057X1204000411.
- Background: PubMed 34888158Bellgardt M, Ozcelik D, Breuer-Kaiser AFC, Steinfort C, Breuer TGK, Weber TP, Herzog-Niescery J. Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome. World J Crit Care Med. 2021 Nov 9;10(6):323-333. doi: 10.5492/wjccm.v10.i6.323. eCollection 2021 Nov 9.
- Background: PubMed 29508167Rand A, Zahn PK, Schildhauer TA, Waydhas C, Hamsen U. Inhalative sedation with small tidal volumes under venovenous ECMO. J Artif Organs. 2018 Jun;21(2):201-205. doi: 10.1007/s10047-018-1030-9. Epub 2018 Mar 5.
- Background: PubMed 23545542Ferrando C, Aguilar G, Piqueras L, Soro M, Moreno J, Belda FJ. Sevoflurane, but not propofol, reduces the lung inflammatory response and improves oxygenation in an acute respiratory distress syndrome model: a randomised laboratory study. Eur J Anaesthesiol. 2013 Aug;30(8):455-63. doi: 10.1097/EJA.0b013e32835f0aa5.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eddy Fan, MD contact
Diana Morales Castro, MD principal investigator
University Health Network, Toronto
Questions about this trial
What is this clinical trial studying?
A study testing Sevoflurane vaporized in ECMO machines in people with Respiratory Failure, run by University Health Network, Toronto.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Diana Morales Castro, MD (+1 416 340-3131 ext. 3420, diana.moralescastro@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sevoflurane plasma concentrations (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05680545, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.