Clinical trial NCT06202989: Multiprofen-CC™ to Reduce Pain After Total Knee Arthroplasty
Official title: Multiprofen-CC™ to Reduce Pain After Total Knee Arthroplasty: a Blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Postsurgical Pain
Keywords: Osteoarthritis, Knee
Arthroplasty, Replacement, Knee
Analgesics, Opioid
Lead sponsor: KAZM Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: McMaster University
First posted: 2024-01-12
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2-arm parallel group randomized placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute postoperative pain
timeFrame: 1, 2, 3, 4, 5, and 6 weeks postop
Secondary outcomes:
measure: Time to opioid cessation
timeFrame: 6 weeks postop
measure: Satisfaction with Pain Management
timeFrame: 6 weeks postop
measure: Safety - Adverse events
timeFrame: up to 6 weeks postop
measure: Cumulative opioid use measured in Morphine Equivalent Dose (MED)
timeFrame: up to 6 weeks postop
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Oakville
country: Canada
facility: Oakville Trafalgar Memorial Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Giuseppe Valente, MD, MMgt, FRCSC
role: PRINCIPAL_INVESTIGATOR
References: