Overview

This trial is active, not recruiting.

Conditions cardiac surgical procedures, cardiopulmonary bypass, systemic inflammatory response syndrome
Treatments methylprednisolone, placebo
Phase phase 4
Sponsor Population Health Research Institute
Collaborator Canadian Institutes of Health Research (CIHR)
Start date June 2007
End date February 2014
Trial size 7507 participants
Trial identifier NCT00427388, SIRS 2007

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?

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
500 mg of methylprednisolone divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation
methylprednisolone
Given by IV in 2 doses (250 mg each dose for a total of 500 mg)
(Placebo Comparator)
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
placebo
Given in 2 IV doses (approximately 4 ml of 0.9% normal saline solution in each dose)

Primary Outcomes

Measure
Mortality at 30 days
time frame: 30 days post-randomization
Composite
time frame: 30 days post-randomization

Secondary Outcomes

Measure
MI or Mortality at 30 days
time frame: 30 days post-randomization
Mortality at 6 months
time frame: 6 months post-randomization
Atrial Fibrillation
time frame: 30 days post-randomization
Transfusion Requirements
time frame: 24 hours post-surgery
Chest Tube Output
time frame: 24 hours post-surgery
ICU and Hospital Length of Stay
time frame: Hospital Discharge
Infection
time frame: 30 days post-randomization
Delirium
time frame: 3 days post-surgery
Wound Complication
time frame: 30 days post-randomization
GI Hemorrhage
time frame: 30 days post-randomization
Insulin Use
time frame: 24 hours post-surgery
Peak Blood Glucose
time frame: 24 hours post-surgery

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase IV Study of Perioperative Steroid's Effects on Death or MI in High-Risk Patients Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass
Principal investigator Salim Yusuf, MD, DPhil
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by McMaster University.