- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00967434
Statin Drugs to Prevent Complications During Surgery (STAR-VaS)
Short Term Atorvastatin Regime for Vasculopathic Surgical (STAR-VaS) Patients Study
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Ontario
-
Ottawa, Ontario, Canada, K1Y4E9
- The Ottawa Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Group A- atorvastatin in pre and postop
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.
|
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
Other Names:
Daily placebo on the preoperative days atorvastatin 80 mg on day of surgery atorvastatin 80 mg daily for up to 7 postoperative days
Other Names:
|
Active Comparator: Group B- Atorvastatin postop
Placebo administered for up to 7 preoperative days, atorvastatin 80 mg administered on day of surgery and daily for up to 7 postoperative days.
|
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
Other Names:
Daily placebo on the preoperative days atorvastatin 80 mg on day of surgery atorvastatin 80 mg daily for up to 7 postoperative days
Other Names:
|
Placebo Comparator: Group C- Placebo
Patients receive placebo daily for up 7 preoperative days, placebo on day of surgery and placebo daily for up to 7 postoperative days.
|
Daily placebo in preoperative period Placebo on day of surgery Daily placebo for up to 7 postoperative days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
C-reactive protein levels at 48 hours postoperatively
Time Frame: 48 hours
|
48 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
perioperative myocardial ischemia as detected by Holter monitoring
Time Frame: 48 hours
|
48 hours
|
perioperative myocardial injury as measured by troponin levels
Time Frame: up to 7 postoperative days
|
up to 7 postoperative days
|
liver enzyme levels
Time Frame: up to 7 postoperative days
|
up to 7 postoperative days
|
myopathy as assessed by CK levels
Time Frame: up to 7 postoperative days
|
up to 7 postoperative days
|
Collaborators and Investigators
Investigators
- Principal Investigator: David T Neilipovitz, MD, The Ottawa Hospital
- Principal Investigator: Greg L Bryson, MD, The Ottawa Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Necrosis
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Myocardial Infarction
- Infarction
- Myocardial Ischemia
- Ischemia
- Inflammation
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
Other Study ID Numbers
- 2006832-01H
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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