Perioperative Dexamethasone to Promote Systemic Pro-Resolution Phenotype for Prevention of Acute and Chronic Pain Post-Total Knee Arthroplasty.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Change in Opioid Consumption
研究概览
简要总结
The purpose of the study is three fold. First to determine the ideal dose of dexamethasone intraoperatively that will reduce acute pain and opioid consumption. Second determine if dexamethasone at the time of surgery reduces chronic pain following total knee arthroplasty and finally determine if a pro-inflammatory environment makes patients susceptible to chronic pain after surgery and can dexamethasone alter this environment. Patients undergoing total knee arthroplasty will be randomized to four groups ( 0mg, 6mg, 12mg and 24mg dexamethasone) and assessments will be made of acute and chronic pain and quality of life measures. Blood samples will be drawn to assess Interleukin levels and for Macrophage sorting. For the primary efficacy endpoint of reduction of opioid consumption over 24 hours after surgery the dexamethasone regimen group will be compared to standard of care group using t-test. For comparisons of the secondary efficacy endpoints, t-test, Chi-square test and Fisher's Exact test will be used. Risks of this study include the risks of venipuncture and intravenous dexamethasone administration.
详细描述
This is a Phase IV single center, prospective, randomized, double-blind, dose response study designed to evaluate the optimum dose of dexamethasone to administer as an analgesic in total knee arthroplasty surgery. Randomization will be performed using computer software and the randomization order will be written and enclosed in envelopes in the study office. A total of 40 patients will be randomized to receive different doses of dexamethasone intravenously at induction of anesthesia with the same dose repeated 24 hours later. The dose groups are: 0mg, 6mg, 12mg, 24mg. The groups will be evenly divided into 10 subjects in each group. Patients will be cared for using established standard of care anesthetic and multi modal analgesia pathway used clinically at Duke University Medical Center. Knee arthroplasty generally occurs in patients over 65 years of age and an inclusion criteria is age 55 years or older is included in the study. Regional anesthesia is more technically challenging in morbidly obese patients. Because of an increased failure rate of regional anesthesia in morbidly obese patients an upper limit BMI of 40 is included in the study design.
Anesthetic regime. The anesthesia will be standard of care apart from the administration of the study drug.
Study Drug. After randomization the first dose of intravenous dexamethasone will be administered by the anesthesia care team immediately before surgery. The subject and study personnel will be blinded to the dose. The patient will be sedated and the study personnel will not be in the operating room. The dose will be recorded on the anesthesia record.
The second dose of dexamethasone will be prescribed by the PI. This will be prescribed electronically to be administered to the subject on the floor 24 hours after the first dose.
Surgery The surgery will proceed normally with no difference for the study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients scheduled to undergo unilateral total knee arthroplasty.
- •American Society of Anesthesiology (ASA) Physical Class 1-
- •BMI <40 kg/m2
排除标准
- •Revision surgery.
- •Bilateral total knee arthroplasty.
- •Unicompartmental knee arthroplasty.
- •Patients with a contraindication to regional anesthesia. This includes abnormal clotting, skin infection in groin or near the back, the presence of neurological disorders or anatomical abnormalities of the vertebral column.
- •Contraindications or known drug interactions with dexamethasone.
- •Use of any of the following medications within the times specified before surgery:
- •Long-acting opioid medication within 3 days.
- •Any opioid medication within 24 hours.
- •Body weight less than 50 kilograms (~110 pounds).
- •Planned administration of another investigational product or procedure during the subject's participation in this study.
- •Suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
- •Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance.
- •Current or historical evidence of any clinically significant disease or condition that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postoperative course.
- •Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures, and expose the subject to an unreasonable risk as a result of participating in this clinical trial, such as: debilitating diseases, acute illnesses, hypotension, partial or complete conduction block, impaired cardiac function (Ejection fraction under 35%), epilepsy, myasthenia gravis), severe renal impairment (creatinine > 1.8), comorbid conditions associated with an immunocompromised status, such as blood dyscrasias, HIV/AIDS, or recent chemotherapy.
研究组 & 干预措施
Dexamethasone 6mg
Patients receive 6mg iv dexamethasone at surgical incision and a repeat dose of 6mg of dexamethasone 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.
干预措施: Dexamethasone (Drug)
Dexamethasone 12mg
Patients receive 12mg iv dexamethasone at surgical incision and a repeat dose of 12mg of dexamethasone 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.
干预措施: Dexamethasone (Drug)
Dexamethasone 24mg
Patients receive 24mg iv dexamethasone at surgical incision and a repeat dose of 24mg of dexamethasone 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.
干预措施: Dexamethasone (Drug)
Placebo
Patients receive a placebo injection of saline at surgical incision and a repeat placebo saline injection 24h after incision. Pain scores and opioid consumption will be assessed using iv opioid patient controlled analgesia totals.
干预措施: Placebo (Other)
结局指标
主要结局
Change in Opioid Consumption
时间窗: 6, 12, 18, 24, 36 hours after surgery
mg of morphine equivalents
Change in Visual Analogue Pain Score
时间窗: 6, 12, 18, 24, 36 hours after surgery
Pain scores at rest and with activity using a verbal rating scales (VRS) of 0-10, where "0" represents no pain and "10" represents worst pain ever.
次要结局
- Change in Functional Status as Measured by Brief Pain Inventory Questionnaire(Baseline at Enrollment, 3 and 6 months after surgery)
- Change in Functional Status as Measured by Western Ontario and McMaster Universities Osteoarthritis Index(30 days, 3 and 6 months following surgery)
- Change in Chronic Pain as Measured by Brief Pain Inventory Questionnaire(Baseline at enrollment, 3 months and 6 months after surgery)