Impact of Chronic Statin Use During Surgery on Inflammation and Infection Rates

NCT00967252 | Completed DMC

• 1 other identifier: 2008526-01H
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Inflammation; Infection; Endothelial Function

Keywords

surgery; inflammation; infection; statins

Outcome Measures

Primary Outcomes (1)

• C-reactive protein levels

  48 hours postoperatively

Secondary Outcomes (2)

• brachial artery reactivity (assessed by ultrasound)

  preoperative compared to 24 hours postoperatively

• Infection

  30 postoperative days

Study Arms (5)

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 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 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 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

non-statin group

Patients who are not taking or cannot take a statin drug who is undergoing high risk surgery

Other: Control

Interventions

Atorvastatin DRUG

Atorvastatin 10 mg daily or equivalent dose in another statin

Also known as: lipitor

atorvastatin 10 mg or equivalent dose

Control OTHER

No statin being taken

non-statin group

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1Y4E9, Canada

Location

MeSH Terms

Conditions

Inflammation; Infections

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• David T Neilipovitz, MD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

• Greg L Bryson, MD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 26, 2009
• First Posted: August 27, 2009
• Study Start: November 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 21, 2011

Record last verified: 2011-07

Locations

CA (1)