Clinical trial NCT00656292: Assessing the Role of "Statin" Therapy and Perioperative Inflammatory Response in Patients Undergoing Major Orthopedic Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Perioperative Inflammatory Response
Keywords: Plasma concentrations of inflammatory markers
C-Reactive Protein (CRP)
Interleukin-6 (IL-6)
Tumor Necrosis Factor-Alpha (TNF)
Aspartate Aminotransferase (AST)
Alanine Aminotransferase (ALT)
Creatine Kinase (CK)
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2008-04-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Median Concentration of Aspartate Aminotransferase (AST)
timeFrame: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
Secondary outcomes:
measure: Median Concentration of Alanine Aminotransferase (ALT)
timeFrame: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
measure: Median Concentration of C-Reactive Protein (CRP)
timeFrame: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
measure: Median Concentration of Creatine Kinase (CK)
timeFrame: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
measure: Median Concentration of Interleukin-6 (IL-6)
timeFrame: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
measure: Median Concentration of Tumor Necrosis Factor-Alpha (TNF)
timeFrame: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic Department of Anesthesiology
name: Michael J. Brown, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic Department of Anesthesiolgy
name: Daryl Kor, M.D.
role: PRINCIPAL_INVESTIGATOR
References: