Effect of Perioperative Duloxetine Administration on Opioid Consumption Following Total Knee Arthroplasty
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Opioid consumption
研究概览
简要总结
Knee replacement surgery for osteoarthritis is a commonly performed procedure in Canada with 75,000 of these surgeries performed each year. Success rate for knee replacement surgery is high but more than 20% of patients are still dissatisfied mainly due to reports of ongoing pain. Pain control following knee surgery is important in order to allow patients to engage in recovery and rehabilitation. The current standard of pain management after surgery centers around the use of opioids which is a concerning practice as highlighted by the opioid epidemic. Duloxetine is an antidepressant that has pain relieving properties and it has been studied in patients undergoing knee replacement surgery. Studies to date have not been designed optimally to demonstrate the full effects of opioid dose reduction and the use of duloxetine as a medication following knee replacement surgery. This research study seeks to start duloxetine before surgery, at the recommended therapeutic dose, and for the duration of the early rehabilitation period. If the study is successful, this low-cost medication can improve satisfaction rates and change the standard way the pain management is typically carried out for patients undergoing the knee replacement surgery.
详细描述
The use of duloxetine around the time of total knee arthroplasty has emerged as a promising intervention to help with pain management after surgery and in particular as an opioid sparing agent. Duloxetine is an antidepressant with serotonin and norepinephrine reuptake inhibition effects that also independently exerts an analgesic effect. Duloxetine is Health Canada approved for several indications including pain arising from osteoarthritis of the knee. Pain inhibition action of duloxetine is believed to be a result of potentiation of descending inhibitory pain pathways within the central nervous system. Existing studies examining duloxetine use at the time of surgery has demonstrated statistically significant but less clinically meaningful impacts on opioid sparing and pain reduction. The deficiencies in study design of existing studies have either underdosed duloxetine (30mg instead of the recommended 60mg) and/or utilized non-standard duration of therapy (started too late, continued for only 2 weeks). This study seeks to definitively address whether duloxetine administered 2 weeks preoperatively at 60mg once daily, in addition to standard analgesic practice, will decrease opioid consumption at 1 week postoperatively.
Prospective, randomized, blinded (investigators, clinicians, participant, data collectors/analysts) trial.
Primary Outcome
•Cumulative opioid consumption at 1 week post-operatively.
Secondary Outcomes
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presence of knee osteoarthritis
- •Planned for elective unilateral total knee arthroplasty
- •ASA I - III
- •Baseline creatinine clearance (CrCl) ≥ 30 mL/min within 60 days prior to enrolment, if available. If not available, verbal report from patient of no known renal disease.
排除标准
- •Lack of patient consent; unlikely to comply with follow-up
- •Presence of contraindications to study drug use:
- •Known hypersensitivity to the drug or components of the product
- •Known liver disease - history of cirrhosis, non-alcoholic steatohepatitis
- •Uncontrolled narrow - angle glaucoma
- •Severe renal impairment (CrCl<30mL/min)
- •Concurrent use of thioridazine
- •Concurrent use of potent CYP1A2 inhibitors (e.g. fluvoxamine) and some quinolone antibiotics (e.g. ciprofloxacin or enoxacin)
- •Concurrent use of antidepressants (e.g. MAOI, SSRI, SNRI, TCA, St. John's Wort, buspirone)
- •Concurrent use of triptan or lithium
- •Chronic and high dose opioid use (>30mg oral morphine equivalent per day)
- •Substance use disorder (cannabis and related products, alcohol use disorder, opioid used disorder, illicit drugs)
- •Uncontrolled hypertension (systolic BP > 180mmHg)
- •Untreated psychiatric illness (e.g. depression, suicidal ideation, bipolar disorder)
- •Involved in worker's compensation case/law suit (verbally declared by patient)
研究组 & 干预措施
Control
Placebo OD for 2 weeks preoperatively then OD for 6 weeks post-surgery.
干预措施: Placebo (Drug)
Intervention
Duloxetine 60mg OD for 2 weeks preoperatively then 60mg OD for 6 weeks post-surgery.
干预措施: Duloxetine (Drug)
结局指标
主要结局
Opioid consumption
时间窗: Cumulative opioid consumption at 1 week post-operatively
Cumulative opioid consumption at 1 week post-operatively
次要结局
- Additional analgesic use: opioid prescription(8 weeks (i.e., duration of study))
- Physical function measured by BPI(Preoperative, 6, 12 weeks and 4.5 months)
- Physical function measured by Oxford Knee Scale(Preoperative, 6, 12 weeks and 4.5 months)
- Range of motion: Physical function(Preoperative, 6, 12 weeks and 4.5 months)
- Emotional function measured by GAD-7(Preoperative, 6, 12 weeks and 4.5 months)
- Emotional function measured by PHQ-9(Preoperative, 6, 12 weeks and 4.5 months)
- Neuropathic pain(6 and 12 weeks post-surgery)
- Chronic post-surgical pain(12 weeks post-surgery)
- Pain at rest and with activity(10-14 days preoperative; 1,6,12 weeks and 4.5 months)
- Additional analgesic use(8 weeks (i.e., duration of study))
- Nausea/vomiting(12 weeks (i.e., duration of study))
- Pain at rest and with activity(10-14 days preoperative; 1,6,12 weeks and 4.5 months)
- Additional analgesic use(8 weeks (i.e., duration of study))
- Additional analgesic use: opioid prescription(8 weeks (i.e., duration of study))
- Physical function measured by BPI(Preoperative, 6, 12 weeks and 4.5 months)
- Physical function measured by Oxford Knee Scale(Preoperative, 6, 12 weeks and 4.5 months)
- Range of motion: Physical function(Preoperative, 6, 12 weeks and 4.5 months)
- Emotional function measured by GAD-7(Preoperative, 6, 12 weeks and 4.5 months)
- Emotional function measured by PHQ-9(Preoperative, 6, 12 weeks and 4.5 months)
- Patient satisfaction(1 week after start of intervention; 1, 6, and 12 weeks after surgery and 4.5 months after surgery)
- Neuropathic pain(6 and 12 weeks post-surgery)
- Chronic post-surgical pain(12 weeks post-surgery)
- Quality of recovery (QoR-15)(1/6/12 weeks and and 4.5 months post-surgery)
- Adverse events(1 week after starting intervention; in hospital at POD1-3, and 1, 6, and 12 weeks post-op.)
研究者
Dr. Howard Meng
Principal Investigator
Sunnybrook Health Sciences Centre