Perioperative HMG-CoA-Reductase-Inhibitors: A Pilot Study Assessing the Role of "Statin" Therapy and Perioperative Inflammatory Response in Patients Undergoing Major Orthopedic Surgery
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Median Concentration of Aspartate Aminotransferase (AST)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Care Provider)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients scheduled for elective major spine surgery (multilevel (2-6 level) open thoracic or lumbar spine surgery with instrumentation)
排除标准
- •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
- •Chlorambucil
- •Minocycline
- •Myochrysine
- •Penicillamine
- •Hydroxychloroquine
- •Leflunomide
- •Any medications listed in 3 or 10 above in the post-operative period
- •Use of Activated protein C at any time during the patients hospitalization
- •Use of anti-inflammatory medications listed below within the last 30 days:
- •Leflunomide
- •Sulfasalazine
- •Mycophenolate
- •Cyclosporine
- •Cyclophosphamide
- •Azathioprine
- •Chlorambucil
- •Minocycline
- •Myochrysine
- •Penicillamine
- •Hydroxychloroquine
- •Methotrexate
研究组 & 干预措施
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.
干预措施: Simvastatin (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Median Concentration of Aspartate Aminotransferase (AST)
时间窗: baseline, at the start of the surgical procedure (0 hrs), 8 hrs, 24 hrs, 48 hrs, 72 hrs
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.
次要结局
- 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)