Postoperative Pain Following Knee Arthroplasty
Conditions
Keywords
Total Knee Arthroplasty, Postoperative Pain, Journavx, Suzetrigine, Opioid, Enhanced Recovery
Brief summary
The goal of this clinical trial is to learn if a non-opioid pain medicine called suzetrigine works to treat pain after total knee replacement surgery in adults. It will also learn about the safety of suzetrigine. The main questions it aims to answer are: Does suzetrigine lower the amount of opioid pain medicine participants use after surgery? Does suzetrigine have any effect on postoperative patient-reported outcomes, including pain scores, range of motion, length of stay, and KOOS/PROMIS surveys? Researchers will compare suzetrigine to a placebo to see if suzetrigine works to treat pain after total knee replacement surgery. Participants will: Take suzetrigine or a placebo by mouth for 14 days after surgery Receive standard pain care, including opioid pain medicine only if needed Report their pain levels using short daily surveys Attend routine follow-up visits after surgery
Detailed description
Post-operative pain management following total knee arthroplasty (TKA) continues to present significant challenges. Despite multimodal Enhanced Recovery After Surgery (ERAS) protocols, over 60% of patients still require opioid medications two weeks after surgery. Given the ongoing opioid epidemic, opioid prescribing is a priority for quality improvement in orthopaedic surgery. High opioid exposure is associated with constipation, nausea, increased risk of falls, hindered rehabilitation, and persistent opioid use. Furthermore, opioid use within the early postoperative period following TKA is associated with a dose-dependent increased risk of periprosthetic joint infection and venous thromboembolic events. With over 700,000 TKAs performed each year in the United States, these complications represent not only individual patient risks but also broader public health concerns. Multimodal pain regimens consisting of alternative analgesics such as acetaminophen, NSAIDs, and gabapentinoids may only provide partial relief for patients, leaving opioids as the default choice for managing breakthrough pain, despite their undesirable side effect profile and addictive potential.\[8\] This ongoing challenge underscores the urgent need to identify safer and more effective pain management strategies. Suzetrigine (Brand name: Journavx), a selective inhibitor of NaV1.7/NaV1.8 channels, has emerged as a promising candidate. Phase 3 clinical trials have shown that suzetrigine provides pain relief comparable to opioids, effectively reducing pain scores, with fewer adverse effects. Data from phase 2 bunionectomy studies further support its opioid-sparing capabilities. Unlike opioids, suzetrigine does not cause sedation, respiratory depression, or dependency. Its favorable pharmacokinetic properties, including renal-sparing metabolism and convenient oral twice-daily dosing, make it well-suited for integration into ERAS protocols. The purpose of this randomized controlled trial is to assess whether suzetrigine can serve as an effective, opioid-sparing analgesic after TKA. If the results are successful, this could lead to expanded FDA labeling, wider adoption in orthopaedic practices, and a significant decrease in opioid prescriptions on a large scale.
Interventions
DRUGSuzetrigine
Suzetrigine is an oral, non-opioid pain medication that works by blocking specific sodium channels involved in pain signaling. In this study, participants assigned to the suzetrigine group will receive a 100 milligram oral dose in the preoperative area, immediately prior to undergoing the procedure, followed by 50 milligrams taken by mouth twice daily for 14 days after surgery. Suzetrigine will be given in addition to standard postoperative pain care, including acetaminophen, nonsteroidal anti-inflammatory drugs when appropriate, and opioid pain medication only if needed for breakthrough pain.
DRUGPlacebo
The placebo is an oral tablet designed to look like the suzetrigine tablet but contains no active drug. In this study, participants assigned to the placebo group will receive a tablet in the preoperative area immediately prior to the procedure, followed by placebo tablets taken by mouth twice daily for 14 days after surgery. The placebo will be given in addition to standard postoperative pain care, including acetaminophen, nonsteroidal anti-inflammatory drugs when appropriate, and opioid pain medication only if needed for breakthrough pain.
Sponsors
AdventHealth
American Association of Hip and Knee Surgeons
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Scheduled for elective, unilateral primary total knee arthroplasty * Able to tolerate oral medications after surgery
Exclusion criteria
* Revision or bilateral total knee arthroplasty * American Society of Anesthesiologists (ASA) physical status classification greater than 3 * Severe renal impairment (estimated glomerular filtration rate less than 15 mL/min/1.73 m²) * Severe hepatic impairment (Child-Pugh Class C) * Chronic opioid use of 30 morphine milligram equivalents per day or greater for more than 3 months * Pregnancy or breastfeeding * Seizure disorder or known hypersensitivity to suzetrigine * Use of medications contraindicated with CYP3A metabolism * Active gastrointestinal ulcer or bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Usage | 2 weeks | MME of opioid usage |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Pain Rating Scale Scores | 2 Weeks | Pain will be measured using the Numeric Pain Rating Scale (NPRS), a patient-reported pain scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain imaginable. Higher scores indicate worse pain. NPRS scores will be collected daily for the first 14 days after surgery and summarized over the 2-week postoperative period. |
| Range of Motion | 2 Weeks | Knee range of motion will be assessed using goniometric measurement of knee flexion, performed by a trained care provider during routine postoperative evaluations. Range of motion reflects the degree of knee movement achieved after surgery. Greater range of motion indicates better functional recovery. Measurements will be obtained at discharge and at the 2-week postoperative visit. |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Score | 2 Weeks | Pain-related interference with daily activities will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference questionnaire. This is a standardized patient-reported outcome measure that evaluates the extent to which pain interferes with physical, social, and emotional functioning. Higher scores indicate worse pain interference. |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score | 2 Weeks | Physical function will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function questionnaire, a validated patient-reported measure of mobility and functional ability. Higher scores indicate better physical function. |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | 2 Weeks | Knee-related symptoms and function will be assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. This patient-reported outcome measure evaluates pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life. Higher scores indicate better knee-related outcomes. |
| Incidence of Treatment-Emergent Side Effects | 2 Weeks | The occurrence of treatment-emergent side effects will be assessed during the first 2 weeks after surgery. Side effects monitored include nausea, vomiting, constipation, dizziness, sedation, pruritus, headache, weakness, and worsened sleep. The outcome will be reported as the number of participants experiencing one or more side effects during the assessment period. A higher number of participants with side effects indicates worse tolerability. |
Contacts
CONTACTRamakanth Yakkanti, MD
PRINCIPAL_INVESTIGATORRamakanth Yakkanti, MD
Rothman Orthopaedics Florida at AdventHealth
Outcome results
None listed