Postsurgical Pain
Conditions
Keywords
Osteoarthritis, Knee, Arthroplasty, Replacement, Knee, Analgesics, Opioid
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.
Interventions
Multiprofen-CC™ \[ketoprofen (10%), baclofen (5%), amitriptyline (2%), and lidocaine (5%)\] Dose: 1.0g, 3 times per day for 6 weeks after surgery
The placebo is the base cream with no medicinal ingredients to be applied 3 times per day for 6 weeks after surgery
Sponsors
KAZM Pharmaceuticals Inc.
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All included patients, research personnel, healthcare providers and outcome assessors will be blinded to the treatment allocation.
Intervention model description
2-arm parallel group randomized placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute postoperative pain | 1, 2, 3, 4, 5, and 6 weeks postop | Daily pain score on 0-10 numeric rating scale from postop day 1 up to 6 weeks postop. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to opioid cessation | 6 weeks postop | Use of opioids at 6 weeks postop and timing of opioid cessation. |
| Cumulative opioid use measured in Morphine Equivalent Dose (MED) | up to 6 weeks postop | Cumulative opioid use up to 6 weeks postop measured in MED |
| Weekly Opioid Use | 6 weeks postop | Weekly opioid use over 6 weeks postop, measured as total MED per postoperative week derived from the daily medication diary. |
| Satisfaction with Pain Management | 6 weeks postop | Satisfaction with pain management measured on a 0-10 numeric rating scale (NRS; higher score is better). |
| Safety - Adverse events | up to 6 weeks postop | Knee-related, surgery-related, and IP or pain medication related AEs, plus all SAEs for 6 weeks postop. |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORGiuseppe Valente, MD, MMgt, FRCSC
McMaster University
Outcome results
None listed