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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Acute Pain; Neuropathic Pain; Knee Pain Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Venlafaxine 37.5 MG

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sarah J Zhang, PhD; Phone Number: 4086666312; Email: jingying.zhang@ucsf.edu
• Study Contact Backup: Name: Matthias Behrends, MD; Phone Number: 4155143761; Email: matthias.behrends@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
      • Contact: Sarah Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery.	Drug: Placebo; placebo filled pill daily for 7 consecutive days.; Other Names: control
Experimental: Venlafaxine; 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; venlafaxine 37.5mg daily for 7 consecutive days.; 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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Orthopedic Research and Education Foundation
• Investigators: Principal Investigator: Matthias Behrends, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Chronic Pain; Neuralgia; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
• Other Study ID Numbers: 20-32595

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share our raw clinical data with other researchers.
• IPD Sharing Time Frame: For the entire study period
• IPD Sharing Access Criteria: Non-profit and research purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No