Statin Drugs to Prevent Complications During Surgery (STAR-VaS)
Primary Purpose
Inflammation, Myocardial Infarction, Myocardial Ischemia
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Atorvastatin
Atorvastatin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Inflammation focused on measuring infarction, ischemia, surgery, perioperative, statins
Eligibility Criteria
Inclusion Criteria:
- elective high-risk surgery defined by use of the POISE criteria
- over 45 years of age
Exclusion Criteria:
- lack of informed consent
- contraindication to statin (i.e. liver insufficiency or cirrhosis, active muscular disorder or myopathy, or previous adverse reaction to statin)
- pregnant
- enrolled in another conflicting study
- previously enrolled in STAR VaS
- presently using a statin drug
Sites / Locations
- The Ottawa Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Group A- atorvastatin in pre and postop
Group B- Atorvastatin postop
Group C- Placebo
Arm Description
Atorvastatin 80 mg administered daily for at least 7 preoperative days, 80 mg on day of surgery and 80 mg daily for up to 7 postoperative days.
Placebo administered for up to 7 preoperative days, atorvastatin 80 mg administered on day of surgery and daily for up to 7 postoperative days.
Patients receive placebo daily for up 7 preoperative days, placebo on day of surgery and placebo daily for up to 7 postoperative days.
Outcomes
Primary Outcome Measures
C-reactive protein levels at 48 hours postoperatively
Secondary Outcome Measures
perioperative myocardial ischemia as detected by Holter monitoring
perioperative myocardial injury as measured by troponin levels
liver enzyme levels
myopathy as assessed by CK levels
Full Information
NCT ID
NCT00967434
First Posted
August 26, 2009
Last Updated
June 11, 2018
Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Anesthesiologists' Society, Heart and Stroke Foundation of Ontario
1. Study Identification
Unique Protocol Identification Number
NCT00967434
Brief Title
Statin Drugs to Prevent Complications During Surgery
Acronym
STAR-VaS
Official Title
Short Term Atorvastatin Regime for Vasculopathic Surgical (STAR-VaS) Patients Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Anesthesiologists' Society, Heart and Stroke Foundation of Ontario
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Patients undergoing non-cardiac surgery frequently experience perioperative cardiac complications that may be due to excess inflammatory reactions. Lipid lowering drugs called HMG-CoA reductase inhibitors or statins, have anti-inflammatory effects. Although favourable evidence suggests these drugs could also prevent perioperative cardiac complications, definitive evidence of anti-inflammatory effects and benefit is lacking. The purpose of this study to measure the impact of a atorvastatin on patients undergoing surgery. It will attempt to determine the speed of drug effect as measured by the impact the drug has on the levels of the inflammatory mediator called C-reactive protein after surgery. It is hypothesized that the perioperative use of atorvastatin will safely reduce the postoperative rise in CRP levels at 48 hours after elective vascular surgery. This effect, would then translate into a reduction of adverse perioperative complications including reduction in postoperative myocardial ischemia episodes (as measured through Holter monitoring).
Detailed Description
Despite modern improvements in operative care, non-cardiac surgery is still associated with significant and costly cardiac complications. The incidence of major perioperative cardiac events varies, ranging from 1% in unselected populations to 15% or more in vascular surgical patients. An estimated 2 million North Americans yearly experience a perioperative cardiac event with an associated mortality of 30-50% and financial burden of over 20 billion dollars. Best evidence suggests that medical optimization is the preferred strategy to reduce the risks. There exists favorable physiologic evidence and promising clinical observations that statin drugs may prevent perioperative complications. We propose a randomized controlled trial to evaluate short-term atorvastatin versus placebo on inflammatory changes and myocardial ischemia in patients undergoing high-risk non-cardiac surgery.
The traditional belief on the etiology of perioperative myocardial events has been that supply-demand discrepancies due to hypotension or hypoxia compromise cardiac oxygen delivery thus resulting in myocardial ischemia and infarction are in dispute. Therapies that target supply-demand imbalance, including perioperative beta-blockers, have been disappointing. Emerging evidence now suggests that most perioperative cardiac events are similar to non-operative events where rupture of coronary plaques and thrombosis are central to the development of acute coronary events. Key elements to plaque rupture are inflammation and endothelial dysfunction. Elevated inflammatory markers, particularly C-reactive protein is associated with adverse cardiac events. Drugs known as statins offer benefits beyond their traditional improvement of lipid levels. Statins have so-called pleiotropic effects that include anti-inflammatory, endothelial function changes and plaque stabilization. Atorvastatin, a statin with a good safety profile, is particularly effective at improving inflammatory levels and decreasing cardiac events including death.
Perioperatively, elevated C-reactive protein levels after surgery are associated with perioperative complications including cardiac events. Thus, strategies to control perioperative inflammation may reduce complications. Retrospective studies and small prospective studies suggest that statins would reduce perioperative complications but definitive evidence is lacking. Questions regarding dose and timing of dosing is unclear. Likewise, little is proven on the potential pathophysiology of atorvastatin on reducing perioperative myocardial events. Our hypothesis is that atorvastatin use will reduce the postoperative rise in CRP levels at 48 hours.
Eligible non-cardiac surgical patients will be randomized into 3 groups with 3 stages of treatment; namely stage 1 (preoperative period up to 7 days), stage 2 (immediate preoperative), and stage 3 (first 7 postoperative days). Group A will receive atorvastatin in all 3 stages. Group B receives placebo in stage 1 but atorvastatin stages 2 and 3. Group C receives placebo in all 3 stages. Atorvastatin dose in all cases will be 80 mg. C-reactive protein and lipid levels assess statin effects. Safety is assessed by liver enzymes and CK levels. Myocardial events assessed by troponin T, ECG and Holter monitoring. Follow-up at 6 months will be done.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation, Myocardial Infarction, Myocardial Ischemia
Keywords
infarction, ischemia, surgery, perioperative, statins
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A- atorvastatin in pre and postop
Arm Type
Active Comparator
Arm Description
Atorvastatin 80 mg administered daily for at least 7 preoperative days, 80 mg on day of surgery and 80 mg daily for up to 7 postoperative days.
Arm Title
Group B- Atorvastatin postop
Arm Type
Active Comparator
Arm Description
Placebo administered for up to 7 preoperative days, atorvastatin 80 mg administered on day of surgery and daily for up to 7 postoperative days.
Arm Title
Group C- Placebo
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo daily for up 7 preoperative days, placebo on day of surgery and placebo daily for up to 7 postoperative days.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Other Intervention Name(s)
lipitor
Intervention Description
atorvastatin 80 mg daily for at least 7 preoperative days atorvastatin 80 mg on day of surgery atorvastatin 80 mg daily for up to 7 postoperative days
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Other Intervention Name(s)
Lipitor
Intervention Description
Daily placebo on the preoperative days atorvastatin 80 mg on day of surgery atorvastatin 80 mg daily for up to 7 postoperative days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Daily placebo in preoperative period Placebo on day of surgery Daily placebo for up to 7 postoperative days
Primary Outcome Measure Information:
Title
C-reactive protein levels at 48 hours postoperatively
Time Frame
48 hours
Secondary Outcome Measure Information:
Title
perioperative myocardial ischemia as detected by Holter monitoring
Time Frame
48 hours
Title
perioperative myocardial injury as measured by troponin levels
Time Frame
up to 7 postoperative days
Title
liver enzyme levels
Time Frame
up to 7 postoperative days
Title
myopathy as assessed by CK levels
Time Frame
up to 7 postoperative days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
elective high-risk surgery defined by use of the POISE criteria
over 45 years of age
Exclusion Criteria:
lack of informed consent
contraindication to statin (i.e. liver insufficiency or cirrhosis, active muscular disorder or myopathy, or previous adverse reaction to statin)
pregnant
enrolled in another conflicting study
previously enrolled in STAR VaS
presently using a statin drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David T Neilipovitz, MD
Organizational Affiliation
The Ottawa Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Greg L Bryson, MD
Organizational Affiliation
The Ottawa Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y4E9
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
22528165
Citation
Neilipovitz DT, Bryson GL, Taljaard M. STAR VaS--Short Term Atorvastatin Regime for Vasculopathic Subjects: a randomized placebo-controlled trial evaluating perioperative atorvastatin therapy in noncardiac surgery. Can J Anaesth. 2012 Jun;59(6):527-37. doi: 10.1007/s12630-012-9702-z. Epub 2012 Apr 13.
Results Reference
derived
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Statin Drugs to Prevent Complications During Surgery
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