Statin Drugs to Prevent Complications During Surgery (STAR-VaS)
|ClinicalTrials.gov Identifier: NCT00967434|
Recruitment Status : Unknown
Verified October 2011 by Ottawa Hospital Research Institute.
Recruitment status was: Active, not recruiting
First Posted : August 27, 2009
Last Update Posted : October 26, 2011
|Condition or disease||Intervention/treatment||Phase|
|Inflammation Myocardial Infarction Myocardial Ischemia||Drug: Atorvastatin Drug: Placebo||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Short Term Atorvastatin Regime for Vasculopathic Surgical (STAR-VaS) Patients Study|
|Study Start Date :||December 2007|
|Estimated Primary Completion Date :||December 2011|
|Estimated Study Completion Date :||December 2011|
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 Name: lipitor
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.
Daily placebo on the preoperative days atorvastatin 80 mg on day of surgery atorvastatin 80 mg daily for up to 7 postoperative days
Other Name: Lipitor
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
- C-reactive protein levels at 48 hours postoperatively [ Time Frame: 48 hours ]
- perioperative myocardial ischemia as detected by Holter monitoring [ Time Frame: 48 hours ]
- perioperative myocardial injury as measured by troponin levels [ Time Frame: up to 7 postoperative days ]
- liver enzyme levels [ Time Frame: up to 7 postoperative days ]
- myopathy as assessed by CK levels [ Time Frame: up to 7 postoperative days ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00967434
|The Ottawa Hospital|
|Ottawa, Ontario, Canada, K1Y4E9|
|Principal Investigator:||David T Neilipovitz, MD||The Ottawa Hospital|
|Principal Investigator:||Greg L Bryson, MD||The Ottawa Hospital|