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Steroids In caRdiac Surgery Trial (SIRS Trial)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00427388
Recruitment Status : Unknown
Verified July 2014 by Richard Whitlock, McMaster University.
Recruitment status was:  Active, not recruiting
First Posted : January 29, 2007
Last Update Posted : August 4, 2014
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Richard Whitlock, McMaster University

Tracking Information
First Submitted Date  ICMJE January 26, 2007
First Posted Date  ICMJE January 29, 2007
Last Update Posted Date August 4, 2014
Study Start Date  ICMJE June 2007
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2014)
  • Mortality at 30 days [ Time Frame: 30 days post-randomization ]
  • Composite [ Time Frame: 30 days post-randomization ]
    Incidence of the composite outcome of death, myocardial infarction, stroke, renal failure (KDIGO Stage III acute kidney injury, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines), or respiratory failure within 30 days
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2007)
Composite Death or Myocardial Infarction at 30 days
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2014)
  • MI or Mortality at 30 days [ Time Frame: 30 days post-randomization ]
    Composite of death or significant myocardial infarction within 30 days post-randomization
  • Mortality at 6 months [ Time Frame: 6 months post-randomization ]
    All-cause mortality at 6 months post-randomization
  • Atrial Fibrillation [ Time Frame: 30 days post-randomization ]
    New onset atrial fibrillation within 30 days post-randomization
  • Transfusion Requirements [ Time Frame: 24 hours post-surgery ]
    Transfusion requirements within first 24 hours post-operative
  • Chest Tube Output [ Time Frame: 24 hours post-surgery ]
    Chest tube output within first 24 hours post-operative
  • ICU and Hospital Length of Stay [ Time Frame: Hospital Discharge ]
    Length of ICU stay and hospital stay
  • Infection [ Time Frame: 30 days post-randomization ]
    Infection within 30 days post-randomization
  • Delirium [ Time Frame: 3 days post-surgery ]
    Delirium at day 3 post-operative
  • Wound Complication [ Time Frame: 30 days post-randomization ]
    Wound complication within 30 days post-randomization
  • GI Hemorrhage [ Time Frame: 30 days post-randomization ]
    GI hemorrhage or GI perforation within 30 days post-randomization
  • Insulin Use [ Time Frame: 24 hours post-surgery ]
    Post-operative insulin use within the first 24 hours after surgery
  • Peak Blood Glucose [ Time Frame: 24 hours post-surgery ]
    Peak blood glucose within the first 24 hours after surgery
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2007)
  • New Onset Atrial Fibrillation
  • Length of ICU Stay
  • Length of Hospital Stay
  • Bleeding/Transfusion Requirements
  • Renal Failure
  • Infection
  • Wound Complications
  • Gastrointestinal Complications
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Steroids In caRdiac Surgery Trial (SIRS Trial)
Official Title  ICMJE Phase IV Study of Perioperative Steroid's Effects on Death or MI in High-Risk Patients Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass
Brief Summary SIRS trial is a large simple study in which high-risk patients undergoing cardiac surgery requiring the use of cardiopulmonary bypass (CPB) are randomly allocated to receive a pulse dose of Methylprednisolone or a matching placebo. Cardiopulmonary bypass initiates a systemic inflammatory response that facilitates development of post-operative complications. SIRS will confirm or deny the potential clinical benefits of suppressing this response through the use of systemic steroids. Specifically, does 250 mg of intravenous Methylprednisolone given twice, once on anesthetic induction and again on CPB initiation, result in improved early survival and less myocardial infarction in high-risk cardiac surgery patients requiring CPB?
Detailed Description

Cardiopulmonary bypass (CPB) is a commonly performed surgical procedure with over 500,000 per year in North America. CPB initiates a systemic inflammatory response characterized by both cell and protein activation. Platelets, neutrophils, monocytes, macrophages, coagulation, fibrinolytic, and kallikrein cascades all take part in what results in increased endothelial permeability, vascular, and parenchymal damage. These inflammatory pathways facilitate development of post-operative complications including thrombosis, myocardial injury and infarction, respiratory failure, renal and neurological dysfunction, bleeding disorders, altered liver function and ultimately, multiple organ failure.

In an attempt to minimize the deleterious effects of CPB, investigators have tested a variety of strategies in cardiac surgery ranging from the complete avoidance of CPB, to the use of biocompatible circuits and pharmacologic agents to abrogate the systemic response. Investigators have consistently demonstrated the efficacy of steroids as the most potent anti-inflammatory agent for use during CPB. In fact, from the available evidence, the 2004 AHA guidelines for coronary artery bypass grafting (CABG) "support liberal prophylactic use in patients undergoing extracorporeal circulation". However, the trials that do exist within this literature are focused on biochemical endpoints and are insufficiently powered to make conclusions on hard clinical endpoints. Our pilot RCT, SIRS I, demonstrated the efficacy of a low dose steroid protocol in the suppression of this inflammatory cascade. We hypothesize that this low dose protocol will yield clinical benefit while avoiding the potential adverse effects of steroids which are known to be dose dependent.

The primary aim of the SIRS trial is to determine if perioperative pulse dose Methylprednisolone results in improved early survival and less myocardial infarction in cardiac surgery requiring CPB. Additional secondary aims of the SIRS trial are to determine the effect of steroids on other clinical outcomes including length of stay, new onset atrial fibrillation, transfusion requirements, infectious, wound, and gastrointestinal complications.

The design of the SIRS trial is a prospective multicentre international double-blind placebo controlled randomized clinical trial. The sample size of 7500 patients will have 80% to 90% power to detect a 20-30% RRR for the primary outcome with an α=0.05 (two-sided), anticipating a 6% rate of death in the control arm. Our aim is to have 85 international centers participate which, recruiting at 5 patients per month, would complete recruitment in 36 months. This will be a large trial with a simple design and objective outcomes.

A sub-group of patients will be enrolled in a renal sub-study. This sub-study will determine if the risk of acute kidney injury is lower in patients treated with intravenous steroid versus placebo, if steroids lead to better preservation of kidney function six months after cardiac surgery, and whether the impact of steroid exposure differs in patients with and without pre-operative chronic kidney disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiac Surgical Procedures
  • Cardiopulmonary Bypass
  • Systemic Inflammatory Response Syndrome
Intervention  ICMJE
  • Drug: Methylprednisolone
    Given by IV in 2 doses (250 mg each dose for a total of 500 mg)
  • Other: Placebo
    Given in 2 IV doses (approximately 4 ml of 0.9% normal saline solution in each dose)
Study Arms  ICMJE
  • Experimental: Treatment
    500 mg of methylprednisolone divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation
    Intervention: Drug: Methylprednisolone
  • Placebo Comparator: Placebo
    500 mg of matching placebo (normal saline solution) divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation
    Intervention: Other: Placebo
Publications *

*   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 Unknown status
Actual Enrollment  ICMJE
 (submitted: May 8, 2014)
7507
Original Enrollment  ICMJE
 (submitted: January 26, 2007)
10000
Estimated Study Completion Date  ICMJE August 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age greater than 18 years
  2. Require CPB for any cardiac surgical procedure (such as CABG, Valve, Aorta, or combined procedures)
  3. Must have a EuroSCORE ≥ 6
  4. Provide written informed consent

NOTE: For participating sites in India, China and Hong Kong, the following eligibility criteria will be applied:

  1. Age greater than 18 years
  2. Require CPB for any cardiac surgical procedure (such as CABG, Valve, Aorta, or combined procedures)
  3. Must have at least one of the following:

    1. EuroSCORE greater than or equal to 4 and undergoing valvular surgery
    2. EuroSCORE greater than or equal to 6 and undergoing any other cardiac surgery procedure (i.e. CABG, Aorta)
  4. Provide written informed consent

Exclusion Criteria:

  1. Use of systemic corticosteroids
  2. History of bacterial or fungal infection in last 30 days
  3. Allergy/intolerance to corticosteroids
  4. Will receive Aprotinin
  5. Previous participation in study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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 NCT00427388
Other Study ID Numbers  ICMJE SIRS 2007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard Whitlock, McMaster University
Study Sponsor  ICMJE Population Health Research Institute
Collaborators  ICMJE Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: Salim Yusuf, MD, DPhil PHRI
Principal Investigator: Kevin Teoh, MD, MSc McMaster University
Principal Investigator: Richard P Whitlock, MD, MSc McMaster University
PRS Account McMaster University
Verification Date July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP