Coronary Artery DiseasePhase 4RISCCSNCT01477151
Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery
A Phase 4 study testing Volatile anesthetic in people with Coronary Artery Disease and Valvular Heart Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
Anesthesia practice in the 21st century is increasingly outcomes-oriented and evidence-based, but there remain significant gaps in our knowledge, even for commonly-encountered clinical situations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Valvular Heart Disease
- What is being tested?
- Volatile anesthetic
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 464 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2011to Mar 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Patients must be 18 years or over (There is no upper age limit to enrollment)
- Eligible procedures are: CABG on-pump or off-pump, single valve repair/replacement, or CABG/single valve combined procedures
Who cannot join
- Cardiac surgeries that are not one of the included cases
- Planned extubation in the operating room
- Patients refusing blood products (vis à vis blood sampling)
- Pregnant patients
- Malignant hyperthermia or documented/stated allergy to potent volatile anesthetic agents
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Hospital - London Health Sciences Centre
London, Ontario, N6A5A5
About this study
Official title: Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery: A Prospective Randomized Clinical Trial.
Anesthesia practice in the 21st century is increasingly outcomes-oriented and evidence-based, but there remain significant gaps in our knowledge, even for commonly-encountered clinical situations. Currently, the two most commonly used drugs used for maintenance of anesthesia in cardiac surgical patients are isoflurane and sevoflurane. There is a belief among many cardiac anesthesiologists that sevoflurane is a better cardiac anesthetic than isoflurane, but there is very little data to support this notion. In fact, very little is known about their comparative effects on important patient outcomes because there has not been a large head-to-head prospective randomized clinical trial. This project will supply the data necessary to critically compare the two anesthetics.
Read the detailed description
Current evidence supports the superiority of sevoflurane for myocardial protection during cardiac surgery when compared to total intravenous anesthesia with propofol. However, there is no evidence to suggest that sevoflurane is superior to isoflurane for myocardial protection during cardiac surgery. Sevoflurane may potentially reduce the rate of post-cardiac surgery atrial fibrillation and the time to tracheal extubation compared to isoflurane, but the literature is equivocal on these two important outcomes. Anesthesiologists still frequently use isoflurane for maintenance of cardiac anesthesia, and this is likely because there is substantial uncertainty about whether or not sevoflurane is superior to isoflurane, given the lack of head-to-head RCTs. A large, prospective, pragmatic RCT can ultimately assist clinicians by providing evidence of the non-inferiority (or, possibly the superiority) of one anesthetic compared to the other on important patient outcomes such as ICU length of stay, mortality, renal dysfunction, time to tracheal extubation after cardiac surgery, rates of clinically-important atrial fibrillation, and myocardial damage.
- Conditions
- Coronary Artery Disease, Valvular Heart Disease
- Being tested
- Volatile anesthetic
- Keywords
- isoflurane, sevoflurane, troponin, anesthesia, cardioprotection, preconditioning, cardiac surgery, cardiac anesthesia
- Medical subject headings
- Coronary Artery Disease, Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Volatile anestheticDrug
The intervention in this trial is randomization to either maintenance of anesthesia with sevoflurane or maintenance of anesthesia with isoflurane. The designated volatile anesthetic will be given at a strict minimal amount throughout the entire cardiac surgery (including cardiopulmonary bypass). This regimen (administration throughout the entire operation) has proved to have the greatest efficacy. Apart from this intervention, the anesthetic for patients participating in this trial will not be substantially different from normal practice, as the intention is to allow normal practice (with the exception of the choice of volatile anesthetic agent) to maximize the applicability and external validity of the trial. The management of anticoagulation, cardiac surgical techniques, and other aspects of the procedure will be managed in an unaltered fashion.
No IV drug infusions will be permitted until after protamine administration.
| Study group | Role | What they receive |
|---|---|---|
| sevoflurane | Active comparator | These patients will receive sevoflurane as the volatile anesthetic pre-, during-, and post-cardiopulmonary bypass at a targeted dose of 0.5-2.0 MAC. Receives: Drug: Volatile anesthetic |
| isoflurane | Experimental | These patients will receive isoflurane as the volatile anesthetic pre-, during-, and post-cardiopulmonary bypass at a targeted dose of 0.5-2.0 MAC. Receives: Drug: Volatile anesthetic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation
Measured: 30 days of operation
Secondary outcomes (15)
Postoperative cardiac troponin T
Troponin T sampled at 6 hours after admission to the ICU. The time of sampling will be recorded. The sample will be taken from an indwelling venous or arterial cannula (if one exists) or by venipuncture.
Measured: 6 hours after admission to ICU
Length of stay in the ICU (criteria)
The time from admission in ICU (time 0) until the patient's transfer orders to the floor are enacted.
Measured: Participants will be followed for the duration of ICU stay, an expected average of 1 day
30-day all-cause mortality
A participant who has died for any reason before the end of 30th day after the operation. Day 1 is the first calendar day after first being admitted to the ICU.
Measured: 30 days after operation
Duration of tracheal intubation
The time from being admitted to the ICU (time 0) until the patient's tracheal tube is removed for the first time.
Measured: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Inotrope or vasopressor usage in the ICU
A participant who is treated at any time after the first hour of their ICU stay with an inotropic or vasopressor by infusion.
Measured: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Prolonged inotrope or vasopressor usage in the ICU
Any patient requiring 12 or more continuous hours of any combination of inotropic or vasopressor agent (including the first hour) in the ICU.
Measured: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Peak postoperative serum creatinine
Peak postoperative creatinine as recorded in the hospital chart.
Measured: Participants will be followed for the duration of hospital stay, an expected average of 1 week
New-onset dialysis
Any patient, not previously on dialysis, requiring postoperative dialysis (hemodialysis or peritoneal dialysis).
Measured: Participants will be followed for the duration of hospital stay, an expected average of 1 week
Incidence of new-onset atrial fibrillation
We will capture the proportion of patients who have clinically significant new atrial fibrillation at any time from ICU admission until the end of POD 4. The adjudication of atrial fibrillation will be recorded by the blinded research nurse.
Measured: Until end of post-operative day 4
Incidence of intra-aortic balloon pump usage
The proportion of patients having an intra-aortic balloon pump inserted (either in the operating room or in the ICU).
Measured: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Length of stay in the ICU (actual)
The time from admission in ICU (time 0) until the patient is discharged from the ICU.
Measured: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Length of stay in the hospital (actual)
The time from admission to the ICU until the patient is discharged home from the hospital.
Measured: Participants will be followed for the duration of hospital stay, an expected average of 1 week
Readmission to ICU
Readmission to the ICU for any reason.
Measured: Participants will be followed for the duration of hospital stay, an expected average of 1 week
Perioperative stroke
A new neurological abnormality persisting > 24 hours with documentation by formal neurological examination and evidence of new brain lesions on a brain imaging study.
Measured: Participants will be followed for the duration of hospital stay, an expected average of 1 week
1-year all-cause mortality
A participant who has died for any reason within the first year after the operation. For example, if the operation takes place on June 20 2011, then mortality up to and including June 19 2012 will be counted.
Measured: One year after operation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 464 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Philip Jones, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Philip M Jones, MD MSc, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01477151
- Sponsor's protocol ID
- 16497
- Acronym
- RISCCS
- Status last verified
- Jun 2015
- First submitted
- 16 Nov 2011
- Last updated
- 8 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jones PM, Bainbridge D, Chu MWA, Fernandes PS, Fox SA, Iglesias I, Kiaii B, Lavi R, Murkin JM. Comparison of isoflurane and sevoflurane in cardiac surgery: a randomized non-inferiority comparative effectiveness trial. Can J Anaesth. 2016 Oct;63(10):1128-1139. doi: 10.1007/s12630-016-0706-y. Epub 2016 Jul 27.
PubMed 27465213
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery: A Prospective Randomized Clinical Trial.
- ClinicalTrials.gov ID
- NCT01477151
- Acronym / sponsor ID
- RISCCS / 16497
- Conditions
- Coronary Artery Disease, Valvular Heart Disease
- Keywords
- isoflurane, sevoflurane, troponin, anesthesia, cardioprotection, preconditioning, cardiac surgery, cardiac anesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 464 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 22 Nov 2011 (estimated)
- 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.
Anesthesia practice in the 21st century is increasingly outcomes-oriented and evidence-based, but there remain significant gaps in our knowledge, even for commonly-encountered clinical situations. Currently, the two most commonly used drugs used for maintenance of anesthesia in cardiac surgical patients are isoflurane and sevoflurane. There is a belief among many cardiac anesthesiologists that sevoflurane is a better cardiac anesthetic than isoflurane, but there is very little data to support this notion. In fact, very little is known about their comparative effects on important patient outcomes because there has not been a large head-to-head prospective randomized clinical trial. This project will supply the data necessary to critically compare the two anesthetics.
Detailed description
Current evidence supports the superiority of sevoflurane for myocardial protection during cardiac surgery when compared to total intravenous anesthesia with propofol. However, there is no evidence to suggest that sevoflurane is superior to isoflurane for myocardial protection during cardiac surgery. Sevoflurane may potentially reduce the rate of post-cardiac surgery atrial fibrillation and the time to tracheal extubation compared to isoflurane, but the literature is equivocal on these two important outcomes. Anesthesiologists still frequently use isoflurane for maintenance of cardiac anesthesia, and this is likely because there is substantial uncertainty about whether or not sevoflurane is superior to isoflurane, given the lack of head-to-head RCTs. A large, prospective, pragmatic RCT can ultimately assist clinicians by providing evidence of the non-inferiority (or, possibly the superiority) of one anesthetic compared to the other on important patient outcomes such as ICU length of stay, mortality, renal dysfunction, time to tracheal extubation after cardiac surgery, rates of clinically-important atrial fibrillation, and myocardial damage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sevoflurane | Active comparator | Drug: Volatile anestheticThese patients will receive sevoflurane as the volatile anesthetic pre-, during-, and post-cardiopulmonary bypass at a targeted dose of 0.5-2.0 MAC. |
| isoflurane | Experimental | Drug: Volatile anestheticThese patients will receive isoflurane as the volatile anesthetic pre-, during-, and post-cardiopulmonary bypass at a targeted dose of 0.5-2.0 MAC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients must be 18 years or over (There is no upper age limit to enrollment)
- Eligible procedures are: CABG on-pump or off-pump, single valve repair/replacement, or CABG/single valve combined procedures
Key exclusion criteria (5 listed)
- Cardiac surgeries that are not one of the included cases
- Planned extubation in the operating room
- Patients refusing blood products (vis à vis blood sampling)
- Pregnant patients
- Malignant hyperthermia or documented/stated allergy to potent volatile anesthetic agents
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 |
|---|---|---|
| Volatile anestheticThe intervention in this trial is randomization to either maintenance of anesthesia with sevoflurane or maintenance of anesthesia with isoflurane. The designated volatile anesthetic will be given at a strict minimal amount throughout the entire cardiac surgery (including cardiopulmonary bypass). This regimen (administration throughout the entire operation) has proved to have the greatest efficacy. Apart from this intervention, the anesthetic for patients participating in this trial will not be substantially different from normal practice, as the intention is to allow normal practice (with the exception of the choice of volatile anesthetic agent) to maximize the applicability and external validity of the trial. The management of anticoagulation, cardiac surgical techniques, and other aspects of the procedure will be managed in an unaltered fashion. No IV drug infusions will be permitted until after protamine administration. | Drug | isoflurane, sevoflurane |
Primary outcome
Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation
Time frame: 30 days of operation
15 secondary outcomes
Postoperative cardiac troponin T
Time frame: 6 hours after admission to ICU
Length of stay in the ICU (criteria)
Time frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day
30-day all-cause mortality
Time frame: 30 days after operation
Duration of tracheal intubation
Time frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Inotrope or vasopressor usage in the ICU
Time frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Prolonged inotrope or vasopressor usage in the ICU
Time frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Peak postoperative serum creatinine
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week
New-onset dialysis
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week
Incidence of new-onset atrial fibrillation
Time frame: Until end of post-operative day 4
Incidence of intra-aortic balloon pump usage
Time frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Length of stay in the ICU (actual)
Time frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day
Length of stay in the hospital (actual)
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week
Readmission to ICU
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week
Perioperative stroke
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week
1-year all-cause mortality
Time frame: One year after operation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
- Derived from this study: PubMed 27465213Jones PM, Bainbridge D, Chu MWA, Fernandes PS, Fox SA, Iglesias I, Kiaii B, Lavi R, Murkin JM. Comparison of isoflurane and sevoflurane in cardiac surgery: a randomized non-inferiority comparative effectiveness trial. Can J Anaesth. 2016 Oct;63(10):1128-1139. doi: 10.1007/s12630-016-0706-y. Epub 2016 Jul 27.
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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. This study is not recruiting at the moment.
Philip M Jones, MD MSc principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Volatile anesthetic in people with Coronary Artery Disease and Valvular Heart Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
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 2 inclusion and 5 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: finished, as of the sponsor's last update on 8 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation (time frame: 30 days of operation). 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 NCT01477151, which also lists 1 linked publication.
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 8 Jun 2015.