Impact of Chronic Statin Use During Surgery on Inflammation and Infection Rates (STAR-VaS2)

This study has been completed.
Sponsor:
Information provided by:
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00967252
First received: August 26, 2009
Last updated: July 19, 2011
Last verified: July 2011
  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)

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

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

Secondary Outcome Measures:
  • brachial artery reactivity (assessed by ultrasound) [ Time Frame: preoperative compared to 24 hours postoperatively ] [ Designated as safety issue: No ]
  • Infection [ Time Frame: 30 postoperative days ] [ Designated as safety issue: No ]

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
Study Population

Patients undergoing elective non-cardiac high-risk surgery as defined by the POISE criteria

Criteria

Inclusion Criteria:

  • over 45 years of age
  • able to have a baseline brachial ultrasound test before their day of surgery
  • elective high-risk surgery defined by use of the POISE criteria

Exclusion Criteria:

  • lack of informed consent
  • pregnant
  • contraindication to the brachial artery ultrasound test protocol (i.e. contraindication to 0.4 mg sublingual nitroglycerin)
  • enrolled in another conflicting study
  • previously enrolled in STAR-VaS or STAR-VaS2
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00967252

Locations
Canada, Ontario
The Ottawa Hospital
Ottawa, Ontario, Canada, K1Y4E9
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Principal Investigator: David T Neilipovitz, MD The Ottawa Hospital
Principal Investigator: Greg L Bryson, MD The Ottawa Hospital
  More Information

No publications provided

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

Keywords provided by Ottawa Hospital Research Institute:
surgery
inflammation
infection
statins

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014