Multiprofen-CC™ to Reduce Pain After Total Knee Arthroplasty

Multiprofen-CC™ to Reduce Pain After Total Knee Arthroplasty: A Blinded Randomized Controlled Trial

Total knee arthroplasty is a surgical treatment which involves replacing the damaged articular cartilage of the knee joint with an artificial prosthetic in end-stage knee osteoarthritis. Although total knee arthroplasties are mostly successful, approximately 1 in 5 patients are unsatisfied with their outcomes with 16-33% of patients of patients experiencing lasting pain following total knee arthroplasty.

Multiprofen-CC™ is a compounded topical analgesic currently available to healthcare professionals for prescription in patients experiencing localized musculoskeletal pain. To date there has been no evidence-based guidance generated to evaluate the efficacy of Multiprofen-CC™ in osteoarthritis patients. This study will test, in patients with end-stage knee osteoarthritis undergoing total knee arthroplasty, if the use of topical Multiprofen-CC™ in addition to standard of care pain management is more effective in controlling knee pain and reducing opioid use compared to placebo plus standard care alone.

Study Overview

• Status: Recruiting
• Conditions: Postsurgical Pain
• Intervention / Treatment: Drug: Multiprofen-CC™ plus standard treatment; Other: Placebo plus standard treatment

Detailed Description

Total knee replacement, also known as total knee arthroplasty (TKA), is a surgical procedure aimed at alleviating pain and improving joint function in individuals with severe knee joint damage, often caused by conditions like osteoarthritis (OA) While TKAs generally yield positive results, a significant amount of patients express dissatisfaction with their outcomes, with some continuing to experience persistent pain after surgery. Opioids are very commonly prescribed for postsurgical pan, but they can cause a host of unwanted side effects. Orthopaedic surgeons prescribe opioids more frequently than in any other surgical speciality. This is a rising concern to the healthcare system as it may promote the development of opioid use disorder. There is a need for alternative therapies to opioid prescribing in patients having knee surgery to reduce the extensive health risks associated with opioid medications.

Multiprofen-CC™ is a multimodal topical cream including ingredients ketoprofen (10%), baclofen (5%), amitriptyline (2%), and lidocaine (5%). Healthcare professionals have the option to prescribe it to patients who are encountering localized musculoskeletal pain. To date there has been no evidence-based guidance generated to evaluate the efficacy of Multiprofen-CC™ in OA patients although there is compelling evidence that its medicinal ingredients are effective in pain relief.

The aim of the proposed study is to determine if, in patients with end-stage knee OA undergoing TKA, the use of topical Multiprofen-CC™ in addition to standard of care pain management is more effective in reducing acute post-operative pain during a 6 week follow-up period. Secondary objectives include determining the effects of Multiprofen-CC™ compared to placebo on opioid use, satisfaction with pain management, and we will also identify adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 288
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Breanne Flood, MSc; Phone Number: 905-870-1382; Email: floodbl@mcmaster.ca
• Study Contact Backup: Name: Kim Irish, BSW; Phone Number: 365-336-7598; Email: irishkd@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
      • Contact: Kim Madden, PhD; Phone Number: (289) 237-7380; Email: maddenk@mcmaster.ca
      • Contact: Giuseppe Valente, MD, MMgt, FRCSC; Phone Number: 34861 (905) 521-2100; Email: gvalente@stjosham.on.ca
    • Oakville, Ontario, Canada, L6M 0L8
      • Not yet recruiting
      • Oakville Trafalgar Memorial Hospital
      • Contact: Heather Brien, MD; Phone Number: 905-339-2498

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (18+)
• Undergoing Primary Elective TKA
• Provide informed consent

Exclusion Criteria:

• Administration of any investigational drug in the period of 0 to 45 days before entry into the study
• Pregnancy
• Actively breastfeeding
• Unable to provide informed consent (e.g. cognitive disability)
• Unable or unwilling to follow study protocol (e.g. unwilling to apply the topical treatments as instructed)
• Have a known allergy to ketoprofen, other NSAIDs, baclofen, amitriptyline, or lidocaine, any of the study drugs or their ingredients
• Have a history of substance abuse
• Use daily opioids (other than short acting codeine) for a chronic pain condition other than knee OA
• Are undergoing a revision TKA or are scheduled for a simultaneous bilateral TKA
• Any other condition which, in the opinion of the investigators, is likely to interfere with the successful collection of the measures required for the study
• Diagnosis of uncontrolled hypertension
• Diagnosis of active peptic ulcer disease
• A history of chronic (> 3 months) anticoagulant usage
• History of impaired kidney or liver function
• Have open wounds/cuts and/or skin conditions on the knee area, other than the surgical incision
• Body Mass Index (BMI) > 50kg/m2

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
Experimental: Multiprofen-CC™; Standard care pain medications and topical Multiprofen-CC™ (1g TID) for 6 weeks after surgery	Drug: Multiprofen-CC™ plus standard treatment; Multiprofen-CC™ [ketoprofen (10%), baclofen (5%), amitriptyline (2%), and lidocaine (5%)] Dose: 1.0g, 3 times per day for 6 weeks after surgery
Placebo Comparator: Control; Standard care pain medications and visually identical topical placebo (1g TID) for 6 weeks after surgery	Other: Placebo plus standard treatment; The placebo is the base cream with no medicinal ingredients to be applied 3 times per day for 6 weeks after surgery; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute postoperative pain	Daily pain score on 0-10 numeric rating scale from post-op day 1 up to 6-weeks postop.	1, 2, 3, 4, 5, and 6 weeks postop

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to opioid cessation	Time to opioid cessation	6 weeks postop
Satisfaction with Pain Management	Satisfaction with pain management measured on a 0-10 numeric rating scale (NRS; higher score is better)	6 weeks postop
Safety - Adverse events	Serious and non-serious adverse events	up to 6 weeks postop
Cumulative opioid use measured in Morphine Equivalent Dose (MED)	Cumulative opioid use up to 6 weeks	up to 6 weeks postop

Collaborators and Investigators

• Sponsor: KAZM Pharmaceuticals Inc.
• Collaborators: McMaster University
• Investigators: Principal Investigator: Giuseppe Valente, MD, MMgt, FRCSC, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Osteoarthritis, Knee; Analgesics, Opioid; Arthroplasty, Replacement, Knee
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Postoperative Complications; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Osteoarthritis, Knee
• Other Study ID Numbers: PR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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