Evaluating Suzetrigine for Pain Control Following TKA

January 20, 2026 updated by: Teja Yeramosu, AdventHealth

Evaluating a Non-Opioid Analgesic Strategy for Enhanced Recovery After Total Knee Arthroplasty: A Randomized Controlled Trial of Suzetrigine

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

210

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
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.
Experimental: Suzetrigine/Journavx
Drug: Suzetrigine
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Opioid Usage
Time Frame: 2 weeks
MME of opioid usage
2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numeric Pain Rating Scale Scores
Time Frame: 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.
2 Weeks
Range of Motion
Time Frame: 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.
2 Weeks
Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Score
Time Frame: 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.
2 Weeks
Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score
Time Frame: 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.
2 Weeks
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time Frame: 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.
2 Weeks
Incidence of Treatment-Emergent Side Effects
Time Frame: 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.
2 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth

Collaborators

American Association of Hip and Knee Surgeons

Investigators

  • Principal Investigator: Ramakanth Yakkanti, MD, Rothman Orthopaedics Florida at AdventHealth

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

January 17, 2026

First Submitted That Met QC Criteria

January 20, 2026

First Posted (Actual)

January 22, 2026

Study Record Updates

Last Update Posted (Actual)

January 22, 2026

Last Update Submitted That Met QC Criteria

January 20, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AH-ORTHO-JOURNAVX-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data may not be shared outside the research team. The study includes sensitive health information collected under institutional review board approval, and participant consent does not include public data sharing. Data will be analyzed and reported in aggregate to protect participant privacy.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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