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| Sponsor: | Ottawa Hospital Research Institute |
|---|---|
| Information provided by: | Ottawa Hospital Research Institute |
| ClinicalTrials.gov Identifier: | NCT00967252 |
Purpose
Despite improvements in perioperative care, non-cardiac surgery remains associated with significant and costly complications. Analysis of perioperative deaths in the United Kingdom suggests that roughly 80% are directly attributable to infectious and cardiovascular complications. The best available evidence suggests that medical optimization is the preferred strategy to reduce cardiac risks but there has been no novel strategy to reduce nosocomial infection rates in over 20 years.
Emerging evidence in both the non-operative and operative setting suggest that statin drugs may prevent both infectious and cardiac events. The mechanism(s) of action are not entirely clear but appear to independent of lipid lowering effects and are often referred to as pleiotropic effects. Two key elements of the pleiotropic effects of statins appear to be their anti-inflammatory properties and improved endothelial vascular reactivity. The statin dose required to maximize these effects is unknown. A large observational trial suggests a contradictory dose effect with higher doses associated with reduced infectious complications and lower doses associated with fewer cardiac complications. Doctors therefore still have many unanswered questions about the use of statins in the perioperative setting. Should they be routinely started on all or only certain surgical patients? What dose of statin should be used? If a patient is already on a statin, should their dose be altered perioperatively? The latter question is particularly relevant in light of the marked increase in statin use. Recruitment logs for an ongoing trial demonstrate that over 70% of patients undergoing high-risk surgery were taking a statin but at markedly variable doses. This population presents an ideal opportunity to determine if there is a dose response relationship between statins and pleiotropic effects. We therefore propose an observational study that will determine anti-inflammatory and endothelial effects in high-risk surgical patients on varying doses of a perioperative statin drug.
Atorvastatin diminishes the rise in C-reactive protein (CRP), measured 48 hours after elective vascular surgery, in a dose dependent fashion.
Secondary Hypotheses:
Atorvastatin reduces endothelial dysfunction after elective vascular surgery, as measured by brachial artery ultrasound, in a dose dependent fashion.
| Condition | Intervention |
|---|---|
|
Inflammation Infection Endothelial Function |
Drug: Atorvastatin Other: Control |
| Study Type: | Observational |
| Study Design: | Observational Model: Case-Only Time Perspective: Prospective |
| Official Title: | An Observational Trial of Perioperative Atorvastatin on Inflammatory and Endothelial Function in Patients Undergoing Vascular Surgery (STAR-VaS 2) |
| Estimated Enrollment: | 50 |
| Study Start Date: | November 2008 |
| Study Completion Date: | July 2011 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
|
atorvastatin 10 mg or equivalent dose
Patients already taking atorvastatin 10 mg or equivalent dose in another statin who is undergoing high risk surgery
|
Drug: Atorvastatin
Atorvastatin 10 mg daily or equivalent dose in another statin
Other Name: lipitor
|
|
atorvastatin 20 mg or equivalent dose
Patients already taking atorvastatin 20 mg or equivalent dose in another statin who is undergoing high risk surgery
|
Drug: Atorvastatin
Atorvastatin 20 mg daily or equivalent dose in another statin
Other Name: lipitor
|
|
atorvastatin 40 mg or equivalent dose
Patients already taking atorvastatin 40 mg or equivalent dose in another statin who is undergoing high risk surgery
|
Drug: Atorvastatin
Atorvastatin 40 mg daily or equivalent dose in another statin
Other Name: lipitor
|
|
atorvastatin 80 mg or equivalent dose
Patients already taking atorvastatin 80 mg or equivalent dose in another statin who is undergoing high risk surgery
|
Drug: Atorvastatin
Atorvastatin 80 mg daily or equivalent dose in another statin
Other Name: lipitor
|
|
non-statin group
Patients who are not taking or cannot take a statin drug who is undergoing high risk surgery
|
Other: Control
No statin being taken
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 45 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
Patients undergoing elective non-cardiac high-risk surgery as defined by the POISE criteria
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Canada, Ontario | |
| 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 |
More Information
| Responsible Party: | David Neilipovitz MD FRCPC, The Ottawa Hospital |
| ClinicalTrials.gov Identifier: | NCT00967252 History of Changes |
| Other Study ID Numbers: | 2008526-01H |
| Study First Received: | August 26, 2009 |
| Last Updated: | July 19, 2011 |
| Health Authority: | Canada: Health Canada |
|
surgery inflammation infection statins |
|
Inflammation Pathologic Processes Atorvastatin Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents |
Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Enzyme Inhibitors Lipid Regulating Agents Therapeutic Uses |