Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery (RISCCS)

June 3, 2015 updated by: Philip Jones, Lawson Health Research Institute

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
464

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A5A5
        • University Hospital - London Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: sevoflurane
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.
Drug: Volatile anesthetic

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.
Experimental: isoflurane
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.
Drug: Volatile anesthetic

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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation
Time Frame: 30 days of operation
30 days of operation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Postoperative cardiac troponin T
Time Frame: 6 hours after admission to ICU
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.
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
The time from admission in ICU (time 0) until the patient's transfer orders to the floor are enacted.
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
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.
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
The time from being admitted to the ICU (time 0) until the patient's tracheal tube is removed for the first time.
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
A participant who is treated at any time after the first hour of their ICU stay with an inotropic or vasopressor by infusion.
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
Any patient requiring 12 or more continuous hours of any combination of inotropic or vasopressor agent (including the first hour) in the ICU.
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
Peak postoperative creatinine as recorded in the hospital chart.
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
Any patient, not previously on dialysis, requiring postoperative dialysis (hemodialysis or peritoneal dialysis).
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
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.
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
The proportion of patients having an intra-aortic balloon pump inserted (either in the operating room or in the ICU).
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
The time from admission in ICU (time 0) until the patient is discharged from the ICU.
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
The time from admission to the ICU until the patient is discharged home from the hospital.
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
Readmission to the ICU for any reason.
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
A new neurological abnormality persisting > 24 hours with documentation by formal neurological examination and evidence of new brain lesions on a brain imaging study.
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
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.
One year after operation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lawson Health Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Philip M Jones, MD MSc, Lawson Health Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 16, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 18, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 22, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 8, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16497

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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