Assessing the Role of "Statin" Therapy and Perioperative Inflammatory Response in Patients Undergoing Major Orthopedic Surgery

Perioperative Inflammatory Response Clinical Trial

Official title:

Perioperative HMG-CoA-Reductase-Inhibitors: A Pilot Study Assessing the Role of "Statin" Therapy and Perioperative Inflammatory Response in Patients Undergoing Major Orthopedic Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00656292
• Other study ID #: 06-002881
• Status: Recruiting
• Phase: Phase 4
• First received: April 4, 2008
• Last updated: June 3, 2014
• Start date: April 2008
• Est. completion date: April 2015

Study information

• Verified date: June 2014
• Source: Mayo Clinic
• Contact: Lavonne Liedl
• Phone: 507-284-2511
• Email: liedl.lavonne[@]mayo.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of the present study is to quantify the degree of modulation, if any, in the perioperative inflammatory response associated with statins use. Specifically, we hypothesize that:

In a population of patients undergoing elective orthopedic spine surgery, administration of a specific statin (Simvastatin, Zocor®, Merck Pharmaceuticals), will be associated with a decrease in perioperative inflammatory markers when compared to patients not taking statins

Description:

Previous studies have reported activation of the body's immune system during the perioperative period.1 Typically, this "stress response" is limited and goes unnoticed by the patient and health care team. However, physiologic insults that occur during major surgery may elicit a more pronounced response known as the systemic inflammatory response syndrome (SIRS). Such a response is of great clinical consequence, as it is known to significantly worsen perioperative morbidity and mortality.1 HMG Co-A Reductase Inhibitors (hereafter identified by the common name, "the statins") are potent inhibitors of cholesterol synthesis, and their role in the treatment of atherosclerosis and prevention of coronary artery disease is well documented.2-5 Interestingly, data from animal studies have shown that statins have unique anti-inflammatory properties that are independent of their lipid lowering effects.6 Recently, statin therapy has been associated with a reduced incidence of perioperative cardiovascular and neurologic complications in major vascular and thoracic surgery patients as well as improved outcomes in patients experiencing acute coronary syndrome (ACS).7-13 In all ACS patient populations studied, improvement in outcome has been attributed to coronary plaque stabilization, presumably a result of statins mitigating the local inflammatory response at the level of the coronary plaque.

The purpose of this study is to quantify the magnitude of perioperative inflammation during major orthopedic spine surgery and determine whether statins alter this systemic physiologic response.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• After approval from the Mayo Institutional Review Board, adult (age 18y-80y) patients scheduled for elective major spine surgery [multilevel (2-6 level) open thoracic or lumbar spine surgery with instrumentation] will be randomly assigned to one of the following two groups:

1. non-statin (control) group

2. perioperative statin group

Exclusion Criteria:

Exclusion criteria will include:

1. pregnancy

2. lactating females

3. oral or parenteral corticosteroid use in the past 30 days

4. elevation of AST or ALT > 3x normal

5. elevation of creatinine kinase > 2x normal

6. previous adverse drug reaction to any medication in the statin class

7. current use of fibrates, niacin, itraconazole, ketoconazole, macrolide antibiotics, HIV protease inhibitors and/or nefazodone

8. active liver disease

9. current statin use

10. Anti-inflammatory use of the following medications within the last 30 days:

• Sulfasalazine

• Mycophenolate

• Cyclosporine

• Cyclophosphamide

• Azathioprine

• Chlorambucil

• Minocycline

• Myochrysine

• Penicillamine

• Hydroxychloroquine

• Leflunomide

11. Any medications listed in 3 or 10 above in the post-operative period

12. use of Activated protein C at any time during the patients hospitalization

13. Use of anti-inflammatory medications listed below within the last 30 days:

• Leflunomide

• Sulfasalazine

• Mycophenolate

• Cyclosporine

• Cyclophosphamide

• Azathioprine

• Chlorambucil

• Minocycline

• Myochrysine

• Penicillamine

• Hydroxychloroquine

• Methotrexate

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Perioperative Inflammatory Response

Intervention

Drug:
• simvastatin
40 mg po/NG every day for 6 days
• placebo
1 pill po/NG every day x 6 days

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Administration of a specific statin (Simvastatin, Zocor®, Merck Pharmaceuticals), will be associated with a decrease in perioperative inflammatory markers when compared to patients not taking statins.		7 days	No

External Links

•   Mayo Clinic Clinical Trials