Steroids In caRdiac Surgery Trial (SIRS Trial)
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?
Cardiac Surgical Procedures
Systemic Inflammatory Response Syndrome
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase IV Study of Perioperative Steroid's Effects on Death or MI in High-Risk Patients Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass|
- Mortality at 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- MI or Mortality at 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- Mortality at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Estimated Study Completion Date:||July 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
500 mg of methylprednisolone divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation
Given by IV in 2 doses (250 mg each dose for a total of 500 mg)
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
Given in 2 IV doses (approximately 4 ml of 0.9% normal saline solution in each dose)
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 40 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.
|Contact: Richard P Whitlock, MD, MSc||905 527 4322 ext firstname.lastname@example.org|
|Contact: Jessica C Vincent||905 527 4322 ext email@example.com|
|Hamilton General Hospital||Recruiting|
|Hamilton, Ontario, Canada, L8L 2X2|
|Contact: Richard Whitlock, MD 905-527-4322 ext 40305 firstname.lastname@example.org|
|Principal Investigator:||Salim Yusuf, MD, DPhil||PHRI|
|Principal Investigator:||Kevin Teoh, MD, MSc||McMaster University|
|Principal Investigator:||Richard P Whitlock, MD, MSc||McMaster University|