The Use of Venlafaxine in Reducing Pain in Primary Total Knee Replacement

Study Overview
=================
Brief Summary
-----------------
Patients experience pain after their knee replacement surgery - and some may continue to experience persistent pain long after their knee replacement surgery. Traditional pain management strategies reply on pain medication such as opioids for pain control. However, these drugs do not work well for pain associated with movement or the the nerve pain (tingling, electrical sensations) after surgery. In addition, opioids are associated with significant side effects such as nausea, vomiting, respiratory depression, depression, cognitive dysfunction and risk of persistent opioid use. Neuropathic pain medications, such as venlafaxine are effective in managing nerve pain. Recent studies also support its potential role in acute pain management. Here, we propose a prospective randomized clinical trial 1) to evaluate the efficacy of Venlafaxine in reducing pain intensity and opioid consumption at post-operative day 1 (POD1) and 1- week after surgery, and 2) to examine whether the use of Venlafaxine will reduce the incidents of chronic postsurgical pain in TKA patients at 3-month time point.

Detailed Description
-----------------
Patients meeting the inclusion criteria will be randomized to receive either Venlafaxine extended release (ER) 37.5 mg/d or a placebo on the day of surgery and continue the treatment for 7 days after surgery. The primary outcomes include pain severity score (numeric rating scale, NRS) and consumption of morphine miligram equivalent (MME) at 24 hours. The secondary outcome will measure MME and NRS at postoperative day 7. In addition, the disability scale and perceived function 3 months after surgery will be compared to the baseline level by using PROMIS (Patient-Reported Outcomes Measurement Information System)10 Global Health, KOOS, JR. (Knee injury and Osteoarthritis Outcome Score Short Form), and VR-12 (Veterans RAND 12 Item Health Survey) Scale.

Official Title
-----------------
The Use of Venlafaxine in Reducing Acute Post-Surgical Pain and Opioid Consumption in Primary Total Knee Replacement

Conditions
-----------------
Acute Pain, Chronic Pain, Knee Pain Chronic, Neuropathic Pain

Intervention / Treatment
-----------------
* Drug: Venlafaxine 37.5 MG
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult (male and female) subjects aged 18 to 75, English speaking, are scheduled for primary total knee arthroplasty with planned spinal anesthesia with saphenous peripheral nerve block at the adductor canal. Exclusion Criteria: general anesthesia, hepatic & renal failure, history of diabetic peripheral neuropathic pain, chronic opioid use, concurrent use of antidepressants, triptans, and/or linezolid, allergy to the study medications, prior knee surgery, BMI > 40, bleeding disorders, history of recent falls, concurrent benzodiazepine use.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery. | Drug: Placebo<br>* placebo filled pill daily for 7 consecutive days.<br>* Other names: control;|
| Experimental: Venlafaxine<br>Subjects in venlafaxine arm will receive venlafaxine 37.5mg daily for 7 consecutive days starting on day of primary arthroplasty surgery. | Drug: Venlafaxine 37.5 MG<br>* venlafaxine 37.5mg daily for 7 consecutive days.<br>* Other names: SNRI analgesia;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative 24 hour total opioid consumption | morphine miligram equivalent | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain numeric rating scale at 24 hours post operatively | Pain Scores will be measured on the Numerical Rating Scale (NRS), the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. | 24 hours | 
| Pain severity and interference at 7 days post operatively | The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.The BPI scale defines pain as follows:1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain. | 7 days | 
| Pain severity and interference at 3 months post operatively | The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.The BPI scale defines pain as follows:1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain. | 3 months | 
| Functionality at 7 days postoperatively | Knee injury and osteoarthritis outcome score short form: Patient-Reported Outcomes Measurement Information System (PROMIS), item health survey. The PROMIS Global-10 is a 10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The average Score is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient. | 7 days | 
| Functionality at 7 days postoperatively | Knee injury and osteoarthritis outcome score short form, veterans RAND 12 (VR12) item health survey. The results of the VR-12 are summarized as two scores - a Mental Component Score (MCS) and a Physical Component Score (PCS). The United States population average PCS and MCS are both 50 points. The United States population standard deviation is 10 points. Therefore, each increment of 10 points above or below 50 corresponds to one standard deviation away from the population average. | 7 days | 
| Functionality at 3 months postoperatively | Knee injury and osteoarthritis outcome score short form: Patient-Reported Outcomes Measurement Information System (PROMIS), item health survey. The PROMIS Global-10 is a 10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The average Score is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient. | 3 months | 
| Functionality at 3 months postoperatively | Knee injury and osteoarthritis outcome score short form, veterans RAND 12 (VR12) item health survey. The results of the VR-12 are summarized as two scores - a Mental Component Score (MCS) and a Physical Component Score (PCS). The United States population average PCS and MCS are both 50 points. The United States population standard deviation is 10 points. Therefore, each increment of 10 points above or below 50 corresponds to one standard deviation away from the population average. | 3 months | 
| Opioid consumption at 7 days postoperatively | morphine miligram equivalent | 7 days | 
| Opioid consumption at 3 months postoperatively | morphine miligram equivalent | 3 months |