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

NCT00656292 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 06-002881
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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

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)

Outcome Measures

Primary Outcomes (1)

• Median Concentration of Aspartate Aminotransferase (AST)

  Description: AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 10 to 40 U/L.

  baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs

Secondary Outcomes (5)

• Median Concentration of Alanine Aminotransferase (ALT)

  baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs

• Median Concentration of C-Reactive Protein (CRP)

  baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs

• Median Concentration of Creatine Kinase (CK)

  baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs

• Median Concentration of Interleukin-6 (IL-6)

  baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs

• Median Concentration of Tumor Necrosis Factor-Alpha (TNF)

  baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs

Study Arms (2)

Simvastatin

PLACEBO COMPARATOR

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.

Drug: Simvastatin

Placebo

EXPERIMENTAL

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.

Drug: Placebo

Interventions

Simvastatin DRUG

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

Also known as: Zocor

Simvastatin

Placebo DRUG

1 pill po/NG every day x 6 days

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pregnancy
• Lactating females
• Oral or parenteral corticosteroid use in the past 30 days
• Elevation of AST or ALT \> 3x normal
• Elevation of creatinine kinase \> 2x normal
• Previous adverse drug reaction to any medication in the statin class
• Current use of fibrates, niacin, itraconazole, ketoconazole, macrolide antibiotics, HIV protease inhibitors and/or nefazodone
• Active liver disease
• Current statin use
• Anti-inflammatory use of the following medications within the last 30 days:
• Sulfasalazine
• Mycophenolate
• Cyclosporine
• Cyclophosphamide
• Azathioprine

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Simvastatin

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Michael J. Brown, M.D.
• Organization: Mayo Clinic

Brown.Michael3@mayo.edu

507-284-6317

Study Officials

• Michael J. Brown, M.D.

  Mayo Clinic Department of Anesthesiology

  PRINCIPAL INVESTIGATOR

• Daryl Kor, M.D.

  Mayo Clinic Department of Anesthesiolgy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 4, 2008
• First Posted: April 11, 2008
• Study Start: April 1, 2008
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 19, 2017
• Results First Posted: May 19, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)