Steroids In caRdiac Surgery Trial (SIRS Trial)

NCT00427388 | Unknown Phase 4 DMC

• 1 other identifier: SIRS 2007
• Study Type: interventional
• Target: 7,507
• Locations: 1 country
• Sites: 1

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?

Conditions

Cardiac Surgical Procedures; Cardiopulmonary Bypass; Systemic Inflammatory Response Syndrome

Keywords

Cardiac Surgical Procedures; Cardiopulmonary Bypass; Systemic inflammatory Response Syndrome; Steroid; Myocardial Infarction; Randomized Clinical Trial

Outcome Measures

Primary Outcomes (2)

• Mortality at 30 days

  30 days post-randomization

• Composite

  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

  30 days post-randomization

Secondary Outcomes (12)

• MI or Mortality at 30 days

  30 days post-randomization

• Mortality at 6 months

  6 months post-randomization

• Atrial Fibrillation

  30 days post-randomization

• Transfusion Requirements

  24 hours post-surgery

• Chest Tube Output

  24 hours post-surgery

Study Arms (2)

Treatment

EXPERIMENTAL

500 mg of methylprednisolone divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation

Drug: Methylprednisolone

Placebo

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

Other: Placebo

Interventions

Methylprednisolone DRUG

Given by IV in 2 doses (250 mg each dose for a total of 500 mg)

Treatment

Placebo OTHER

Given in 2 IV doses (approximately 4 ml of 0.9% normal saline solution in each dose)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than 18 years
• Require CPB for any cardiac surgical procedure (such as CABG, Valve, Aorta, or combined procedures)
• Must have a EuroSCORE ≥ 6
• Provide written informed consent
• NOTE: For participating sites in India, China and Hong Kong, the following eligibility criteria will be applied:
• Age greater than 18 years
• Require CPB for any cardiac surgical procedure (such as CABG, Valve, Aorta, or combined procedures)
• Must have at least one of the following:
• EuroSCORE greater than or equal to 4 and undergoing valvular surgery
• EuroSCORE greater than or equal to 6 and undergoing any other cardiac surgery procedure (i.e. CABG, Aorta)
• Provide written informed consent

You may not qualify if:

• Use of systemic corticosteroids
• History of bacterial or fungal infection in last 30 days
• Allergy/intolerance to corticosteroids
• Will receive Aprotinin
• Previous participation in study

Sponsors & Collaborators

• Population Health Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (7)

• Whitlock RP, Young E, Noora J, Farrokhyar F, Blackall M, Teoh KH. Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I. J Surg Res. 2006 May 15;132(2):188-94. doi: 10.1016/j.jss.2006.02.013. Epub 2006 Mar 29.

  PMID: 16566943 BACKGROUND

• Whitlock RP, Rubens FD, Young E, Teoh KH. Pro: Steroids should be used for cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2005 Apr;19(2):250-4. doi: 10.1053/j.jvca.2005.02.010. No abstract available.

  PMID: 15868539 BACKGROUND

• Whitlock R, Teoh K, Vincent J, Devereaux PJ, Lamy A, Paparella D, Zuo Y, Sessler DI, Shah P, Villar JC, Karthikeyan G, Urrutia G, Alvezum A, Zhang X, Abbasi SH, Zheng H, Quantz M, Yared JP, Yu H, Noiseux N, Yusuf S. Rationale and design of the steroids in cardiac surgery trial. Am Heart J. 2014 May;167(5):660-5. doi: 10.1016/j.ahj.2014.01.018. Epub 2014 Mar 1.

  PMID: 24766975 BACKGROUND

• Garg AX, Vincent J, Cuerden M, Parikh C, Devereaux PJ, Teoh K, Yusuf S, Hildebrand A, Lamy A, Zuo Y, Sessler DI, Shah P, Abbasi SH, Quantz M, Yared JP, Noiseux N, Tagarakis G, Rochon A, Pogue J, Walsh M, Chan MT, Lamontagne F, Salehiomran A, Whitlock R; SIRS Investigators. Steroids In caRdiac Surgery (SIRS) trial: acute kidney injury substudy protocol of an international randomised controlled trial. BMJ Open. 2014 Mar 5;4(3):e004842. doi: 10.1136/bmjopen-2014-004842.

  PMID: 24598306 BACKGROUND

• Garg AX, Chan MTV, Cuerden MS, Devereaux PJ, Abbasi SH, Hildebrand A, Lamontagne F, Lamy A, Noiseux N, Parikh CR, Perkovic V, Quantz M, Rochon A, Royse A, Sessler DI, Shah PJ, Sontrop JM, Tagarakis GI, Teoh KH, Vincent J, Walsh M, Yared JP, Yusuf S, Whitlock RP; SIRS Investigators. Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial. CMAJ. 2019 Mar 4;191(9):E247-E256. doi: 10.1503/cmaj.181644.

  PMID: 30833491 DERIVED

• Theriault S, Whitlock R, Raman K, Vincent J, Yusuf S, Pare G. Gene Expression Profiles for the Identification of Prevalent Atrial Fibrillation. J Am Heart Assoc. 2017 Jun 30;6(7):e006057. doi: 10.1161/JAHA.117.006057.

  PMID: 28666990 DERIVED

• Whitlock RP, Devereaux PJ, Teoh KH, Lamy A, Vincent J, Pogue J, Paparella D, Sessler DI, Karthikeyan G, Villar JC, Zuo Y, Avezum A, Quantz M, Tagarakis GI, Shah PJ, Abbasi SH, Zheng H, Pettit S, Chrolavicius S, Yusuf S; SIRS Investigators. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Sep 26;386(10000):1243-1253. doi: 10.1016/S0140-6736(15)00273-1.

  PMID: 26460660 DERIVED

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome; Myocardial Infarction

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Necrosis

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Salim Yusuf, MD, DPhil

  Pranic Healing Research Institute

  PRINCIPAL INVESTIGATOR

• Kevin Teoh, MD, MSc

  McMaster University

  PRINCIPAL INVESTIGATOR

• Richard P Whitlock, MD, MSc

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 26, 2007
• First Posted: January 29, 2007
• Study Start: June 1, 2007
• Primary Completion: February 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 4, 2014

Record last verified: 2014-07

Locations

CA (1)