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

NCT ID: NCT00656292

Last Updated: 2017-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2016-03-31

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.

Conditions

Perioperative Inflammatory Response

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Simvastatin

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.

Group Type: PLACEBO_COMPARATOR

Simvastatin

Intervention Type: DRUG

40 mg po/nasogastric tube (NG) every day for 6 days

Placebo

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

1 pill po/NG every day x 6 days

Interventions

Simvastatin

40 mg po/nasogastric tube (NG) every day for 6 days

Intervention Type: DRUG

Placebo

1 pill po/NG every day x 6 days

Intervention Type: DRUG

Other Intervention Names

Zocor

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Michael Brown

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael J. Brown, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic Department of Anesthesiology

Daryl Kor, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic Department of Anesthesiolgy

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

06-002881

Identifier Type: -

Identifier Source: org_study_id