Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery (RISCCS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Lawson Health Research Institute
Sponsor:
Information provided by (Responsible Party):
Philip Jones, Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT01477151
First received: November 16, 2011
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Valvular Heart Disease
Drug: Volatile anesthetic
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery: A Prospective Randomized Clinical Trial.

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation [ Time Frame: 30 days of operation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Postoperative cardiac troponin T [ Time Frame: 6 hours after admission to ICU ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The time from admission in ICU (time 0) until the patient's transfer orders to the floor are enacted.

  • 30-day all-cause mortality [ Time Frame: 30 days after operation ] [ Designated as safety issue: Yes ]
    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.

  • Duration of tracheal intubation [ Time Frame: Participants will be followed for the duration of ICU stay, an expected average of 1 day ] [ Designated as safety issue: No ]
    The time from being admitted to the ICU (time 0) until the patient's tracheal tube is removed for the first time.

  • 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 ] [ Designated as safety issue: No ]
    A participant who is treated at any time after the first hour of their ICU stay with an inotropic or vasopressor by infusion.

  • 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 ] [ Designated as safety issue: No ]
    Any patient requiring 12 or more continuous hours of any combination of inotropic or vasopressor agent (including the first hour) in the ICU.

  • Peak postoperative serum creatinine [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: No ]
    Peak postoperative creatinine as recorded in the hospital chart.

  • New-onset dialysis [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Any patient, not previously on dialysis, requiring postoperative dialysis (hemodialysis or peritoneal dialysis).

  • Incidence of new-onset atrial fibrillation [ Time Frame: Until end of post-operative day 4 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The proportion of patients having an intra-aortic balloon pump inserted (either in the operating room or in the ICU).

  • 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 ] [ Designated as safety issue: No ]
    The time from admission in ICU (time 0) until the patient is discharged from the ICU.

  • 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 ] [ Designated as safety issue: No ]
    The time from admission to the ICU until the patient is discharged home from the hospital.

  • Readmission to ICU [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Readmission to the ICU for any reason.

  • Perioperative stroke [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    A new neurological abnormality persisting > 24 hours with documentation by formal neurological examination and evidence of new brain lesions on a brain imaging study.

  • 1-year all-cause mortality [ Time Frame: One year after operation ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 464
Study Start Date: November 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01477151

Contacts
Contact: Philip M Jones, MD MSc (519) 685-8500 ext 36306 pjones8@uwo.ca
Contact: Stephanie Fox, BA RRT (519) 685-8500 ext 35031 Stephanie.Fox@LHSC.ON.CA

Locations
Canada, Ontario
University Hospital - London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A5A5
Sub-Investigator: Daniel Bainbridge, MD         
Sub-Investigator: Michael W Chu, MD         
Sub-Investigator: Achal Dhir, MD         
Sub-Investigator: Wojciech Dobkowski, MD         
Sub-Investigator: Philip S Fernandes, BA         
Sub-Investigator: Stephanie Fox, BA         
Sub-Investigator: Christopher C Harle, MBChB         
Sub-Investigator: Ivan Iglesias, MD         
Sub-Investigator: Bob Kiaii, MD         
Sub-Investigator: Ronit Lavi, MD         
Sub-Investigator: John M Murkin, MD         
Sponsors and Collaborators
Lawson Health Research Institute
Investigators
Principal Investigator: Philip M Jones, MD MSc Lawson Health Research Institute
  More Information

No publications provided

Responsible Party: Philip Jones, Principal Investigator, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT01477151     History of Changes
Other Study ID Numbers: 16497
Study First Received: November 16, 2011
Last Updated: June 7, 2012
Health Authority: Canada: Health Canada

Keywords provided by Lawson Health Research Institute:
isoflurane
sevoflurane
troponin
anesthesia
cardioprotection
preconditioning
cardiac surgery
cardiac anesthesia

Additional relevant MeSH terms:
Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Valve Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Anesthetics
Sevoflurane
Isoflurane
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Hematologic Agents
Anesthetics, Inhalation
Anesthetics, General

ClinicalTrials.gov processed this record on September 29, 2014