Statin Drugs to Prevent Complications During Surgery (STAR-VaS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Ottawa Hospital Research Institute.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Canadian Anesthesiologists' Society
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00967434
First received: August 26, 2009
Last updated: October 24, 2011
Last verified: October 2011
  Purpose

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).


Condition Intervention
Inflammation
Myocardial Infarction
Myocardial Ischemia
Drug: Atorvastatin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Short Term Atorvastatin Regime for Vasculopathic Surgical (STAR-VaS) Patients Study

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • C-reactive protein levels at 48 hours postoperatively [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • perioperative myocardial ischemia as detected by Holter monitoring [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • perioperative myocardial injury as measured by troponin levels [ Time Frame: up to 7 postoperative days ] [ Designated as safety issue: No ]
  • liver enzyme levels [ Time Frame: up to 7 postoperative days ] [ Designated as safety issue: Yes ]
  • myopathy as assessed by CK levels [ Time Frame: up to 7 postoperative days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: December 2007
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Atorvastatin
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.
Drug: Atorvastatin
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.
Drug: Placebo
Daily placebo in preoperative period Placebo on day of surgery Daily placebo for up to 7 postoperative days

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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967434

Locations
Canada, Ontario
The Ottawa Hospital
Ottawa, Ontario, Canada, K1Y4E9
Sponsors and Collaborators
Ottawa Hospital Research Institute
Canadian Anesthesiologists' Society
Heart and Stroke Foundation of Ontario
Investigators
Principal Investigator: David T Neilipovitz, MD The Ottawa Hospital
Principal Investigator: Greg L Bryson, MD The Ottawa Hospital
  More Information

No publications provided by Ottawa Hospital Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00967434     History of Changes
Other Study ID Numbers: 2006832-01H
Study First Received: August 26, 2009
Last Updated: October 24, 2011
Health Authority: Canada: Health Canada

Keywords provided by Ottawa Hospital Research Institute:
infarction
ischemia
surgery
perioperative
statins

Additional relevant MeSH terms:
Myocardial Ischemia
Coronary Artery Disease
Infarction
Inflammation
Ischemia
Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Necrosis
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014