Evaluating Suzetrigine for Pain Control Following TKA

NCT07357376 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AH-ORTHO-JOURNAVX-01
• Study Type: interventional
• Target: 210
• Locations: 0 countries
• Sites: N/A

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

Conditions

Postoperative Pain Following Knee Arthroplasty

Keywords

Total Knee Arthroplasty; Postoperative Pain; Journavx; Suzetrigine; Opioid; Enhanced Recovery

Outcome Measures

Primary Outcomes (1)

• Opioid Usage

  MME of opioid usage

  2 weeks

Secondary Outcomes (6)

• Numeric Pain Rating Scale Scores

  2 Weeks

• Range of Motion

  2 Weeks

• Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Score

  2 Weeks

• Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score

  2 Weeks

• Knee Injury and Osteoarthritis Outcome Score (KOOS)

  2 Weeks

Study Arms (2)

Suzetrigine/Journavx

EXPERIMENTAL

Drug: Suzetrigine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

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.

Placebo

Suzetrigine DRUG

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.

Suzetrigine/Journavx

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Scheduled for elective, unilateral primary total knee arthroplasty
• Able to tolerate oral medications after surgery

You may not qualify if:

• 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

Sponsors & Collaborators

• AdventHealth: lead
• American Association of Hip and Knee Surgeons: collaborator

Related Publications (10)

• Hu S, Lyu D, Gao J. Suzetrigine: The first Nav1.8 inhibitor approved for the treatment of moderate to severe acute pain. Drug Discov Ther. 2025 Mar 6;19(1):80-82. doi: 10.5582/ddt.2025.01010. Epub 2025 Feb 27.

  PMID: 40010720 BACKGROUND

• Hang Kong AY, Tan HS, Habib AS. VX-548 in the treatment of acute pain. Pain Manag. 2024 Sep;14(9):477-486. doi: 10.1080/17581869.2024.2421749. Epub 2024 Nov 18.

  PMID: 39552600 BACKGROUND

• Hannon CP, Fillingham YA, Nam D, Courtney PM, Curtin BM, Vigdorchik JM, Buvanendran A, Hamilton WG, Della Valle CJ; AAHKS Anesthesia & Analgesia Clinical Practice Guideline Workgroup. Opioids in Total Joint Arthroplasty: The Clinical Practice Guidelines of the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. J Arthroplasty. 2020 Oct;35(10):2709-2714. doi: 10.1016/j.arth.2020.05.034. Epub 2020 May 26. No abstract available.

  PMID: 32571594 BACKGROUND

• Shichman I, Roof M, Askew N, Nherera L, Rozell JC, Seyler TM, Schwarzkopf R. Projections and Epidemiology of Primary Hip and Knee Arthroplasty in Medicare Patients to 2040-2060. JB JS Open Access. 2023 Feb 28;8(1):e22.00112. doi: 10.2106/JBJS.OA.22.00112. eCollection 2023 Jan-Mar.

  PMID: 36864906 BACKGROUND

• Chung BC, Bouz GJ, Mayfield CK, Nakata H, Christ AB, Oakes DA, Lieberman JR, Heckmann ND. Dose-Dependent Early Postoperative Opioid Use Is Associated with Periprosthetic Joint Infection and Other Complications in Primary TJA. J Bone Joint Surg Am. 2021 Aug 18;103(16):1531-1542. doi: 10.2106/JBJS.21.00045.

  PMID: 34043598 BACKGROUND

• Morris BJ, Mir HR. The opioid epidemic: impact on orthopaedic surgery. J Am Acad Orthop Surg. 2015 May;23(5):267-71. doi: 10.5435/JAAOS-D-14-00163.

  PMID: 25911660 BACKGROUND

• Sabatino MJ, Kunkel ST, Ramkumar DB, Keeney BJ, Jevsevar DS. Excess Opioid Medication and Variation in Prescribing Patterns Following Common Orthopaedic Procedures. J Bone Joint Surg Am. 2018 Feb 7;100(3):180-188. doi: 10.2106/JBJS.17.00672.

  PMID: 29406338 BACKGROUND

• Atwood K, Shackleford T, Lemons W, Eicher JL, Lindsey BA, Klein AE. Postdischarge Opioid Use after Total Hip and Total Knee Arthroplasty. Arthroplast Today. 2021 Jan 30;7:126-129. doi: 10.1016/j.artd.2020.12.021. eCollection 2021 Feb.

  PMID: 33553537 BACKGROUND

• Dawson Z, Stanton SS, Roy S, Farjo R, Aslesen HA, Hallstrom BR, Bicket MC. Opioid Consumption After Discharge From Total Knee and Hip Arthroplasty: A Systematic Review and Meta-Analysis. J Arthroplasty. 2024 Aug;39(8):2130-2136.e7. doi: 10.1016/j.arth.2024.01.063. Epub 2024 Feb 8.

  PMID: 38336301 BACKGROUND

• Shah R, Kuo YF, Westra J, Lin YL, Raji MA. Opioid Use and Pain Control After Total Hip and Knee Arthroplasty in the US, 2014 to 2017. JAMA Netw Open. 2020 Jul 1;3(7):e2011972. doi: 10.1001/jamanetworkopen.2020.11972. No abstract available.

  PMID: 32729917 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Ramakanth Yakkanti, MD

  Rothman Orthopaedics Florida at AdventHealth

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ramakanth Yakkanti, MD

CONTACT

844-407-4070; ramakanth.yakkanti@rothmanortho.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Physician

Study Record Dates

• First Submitted: January 17, 2026
• First Posted: January 22, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share