Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery (RISCCS)

Tracking Information
First Submitted Date ICMJE	November 16, 2011
First Posted Date ICMJE	November 22, 2011
Last Update Posted Date	June 8, 2015
Study Start Date ICMJE	November 2011
Actual Primary Completion Date	March 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 18, 2011)	Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation [ Time Frame: 30 days of operation ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01477151 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 18, 2011)	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.; 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.; 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.; 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.; 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.; 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.; 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.; 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).; 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.; 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).; 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.; 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.; 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.; 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.; 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.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery
Official Title ICMJE	Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery: A Prospective Randomized Clinical Trial.
Brief 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. 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 Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Coronary Artery Disease; Valvular Heart Disease
Intervention ICMJE	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.
Study Arms	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. Intervention: Drug: Volatile anesthetic; 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. Intervention: Drug: Volatile anesthetic
Publications *	Jones PM, Bainbridge D, Chu MW, 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):1128-39. doi: 10.1007/s12630-016-0706-y. Epub 2016 Jul 27.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 18, 2011)	464
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	March 2015
Actual Primary Completion Date	March 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01477151
Other Study ID Numbers ICMJE	16497
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Philip Jones, Lawson Health Research Institute
Study Sponsor ICMJE	Lawson Health Research Institute
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Philip M Jones, MD MSc Lawson Health Research Institute
PRS Account	Lawson Health Research Institute
Verification Date	June 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP