Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery

Coronary Artery Disease Clinical Trial

— RISCCS  

Official title:

Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery: A Prospective Randomized Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01477151
• Other study ID #: 16497
• Status: Completed
• Phase: Phase 4
• First received: November 16, 2011
• Last updated: June 3, 2015
• Start date: November 2011
• Est. completion date: March 2015

Study information

• Verified date: June 2015
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 464
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Valve Diseases
• Myocardial Ischemia
• Valvular Heart Disease

Intervention

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.

Locations

Country	Name	City	State
Canada	University Hospital - London Health Sciences Centre	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation		30 days of operation	Yes
Secondary	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.	6 hours after admission to ICU	Yes
Secondary	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.	Participants will be followed for the duration of ICU stay, an expected average of 1 day	No
Secondary	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.	30 days after operation	Yes
Secondary	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.	Participants will be followed for the duration of ICU stay, an expected average of 1 day	No
Secondary	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.	Participants will be followed for the duration of ICU stay, an expected average of 1 day	No
Secondary	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.	Participants will be followed for the duration of ICU stay, an expected average of 1 day	No
Secondary	Peak postoperative serum creatinine	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	No
Secondary	New-onset dialysis	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	Yes
Secondary	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.	Until end of post-operative day 4	No
Secondary	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).	Participants will be followed for the duration of ICU stay, an expected average of 1 day	No
Secondary	Length of stay in the ICU (actual)	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	No
Secondary	Length of stay in the hospital (actual)	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	No
Secondary	Readmission to ICU	Readmission to the ICU for any reason.	Participants will be followed for the duration of hospital stay, an expected average of 1 week	Yes
Secondary	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.	Participants will be followed for the duration of hospital stay, an expected average of 1 week	Yes
Secondary	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.	One year after operation	Yes