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

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

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.

Who is eligible to participate?

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

Last updated:

6/3/2014

NCT ID:

NCT00656292

IRB Number:

06-002881