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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Michael Brown, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00656292
First received: April 4, 2008
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Perioperative Inflammatory Response
Drug: simvastatin
Drug: placebo
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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. [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: April 2008
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Study groups will receive either statin therapy (simvastatin 40 mg) or placebo two days before surgery -- allowing three doses of simvastatin/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 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
Drug: placebo
1 pill po/NG every day x 6 days
Experimental: 2
Study groups will receive either statin therapy (simvastatin 40 mg) or placebo two days before surgery -- allowing three doses of simvastatin/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 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
Drug: simvastatin
40 mg po/NG every day for 6 days

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00656292

Contacts
Contact: Lavonne Liedl 507-284-2511 liedl.lavonne@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Michael J. Brown, M.D.    507-284-2511    brown.michael3@mayo.edu   
Principal Investigator: Michael J. Brown, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Michael J. Brown, M.D. Mayo Clinic Department of Anesthesiology
Principal Investigator: Daryl Kor, M.D. Mayo Clinic Department of Anesthesiolgy
  More Information

Additional Information:
No publications provided

Responsible Party: Michael Brown, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00656292     History of Changes
Other Study ID Numbers: 06-002881
Study First Received: April 4, 2008
Last Updated: June 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Plasma concentrations of inflammatory markers
(CRP, IL-6, TNF-a), AST, ALT, and CK

Additional relevant MeSH terms:
Simvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 25, 2014