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

Mayo Clinic

Status and phase: Completed; Phase 4

Conditions: Perioperative Inflammatory Response

Treatments: Drug: Placebo; Drug: Simvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT00656292

06-002881

Details and patient eligibility

About

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

Full 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.

Enrollment: 61 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients scheduled for elective major spine surgery (multilevel (2-6 level) open thoracic or lumbar spine surgery with instrumentation)

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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61 participants in 2 patient groups, including a placebo group

Simvastatin

Placebo Comparator group

Description:

Subjects randomized to this arm will receive statin therapy (simvastatin 40 mg) two days before surgery -- allowing three doses of simvastatin before incision -- and these will be continued until patients are either discharged from the hospital or have completed a 3-day postoperative course (6 days of simvastatin therapy), whichever occurs earlier. If patients are unable to take oral medications, the enteral route via nasogastric tube (at our institution, nasogastric tubes are routinely placed for both lumbar and thoracic instrumentation) will be used to deliver either placebo or the statin, as no parenteral form of this drug is currently available.

Treatment:

Drug: Simvastatin

Placebo

Experimental group

Description:

Subjects randomized to this arm will receive placebo two days before surgery -- allowing three doses of placebo before incision -- and these will be continued until patients are either discharged from the hospital or have completed a 3-day postoperative course (6 days of placebo), whichever occurs earlier. If patients are unable to take oral medications, the enteral route via nasogastric tube (at our institution, nasogastric tubes are routinely placed for both lumbar and thoracic instrumentation) will be used to deliver either placebo or the statin, as no parenteral form of this drug is currently available.

Treatment:

Drug: Placebo