Suzetrigine in TKA

NCT07864896 | Recruiting Phase 3 FDA Drug

• 1 other identifier: 2026-0721
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

Total knee replacements are among the most common and painful orthopedic procedures performed worldwide, often requiring intensive analgesia to support early ambulation and recovery. Despite widespread use of multimodal regimens, many patients still rely on opioids, which can cause sedation, nausea, constipation, and long-term dependency. Evaluating suzetrigine in this high-need population may improve recovery trajectories, reduce opioid consumption, and support enhanced recovery protocols. Given the growing surgical volume and the emphasis on opioid-sparing strategies, rigorous investigation of suzetrigine's efficacy in total knee replacement is of high clinical value. In this confirmatory (phase III) trial, patients undergoing primary total knee replacement will be randomized to receive either suzetrigine or placebo for 2 weeks (14 days), with the loading dose administered prior to surgery. The primary outcome is cumulative 48-hour opioid consumption in oral morphine equivalents starting from entry into the post-anesthesia care unit (PACU).

Conditions

Total Knee Replacement; Pain Management; Pain; JOURNAVX; Opioid Consumption, Postoperative; Multimodal Analgesia; Randomized Controlled Study; Total Knee Arthroplasty \(TKA\); Total Knee Replacement Surgery; Total Knee Replacements; Total Knee Replacement Arthroplasty; Suzetrigine; Nav 1.8; Opioid Cessation; Randomized Controlled Trials; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Cumulative opioid consumption within the first 48 hours after TKA starting from post-anesthesia care unit entry (t=0), in oral morphine equivalents (OME)

  From entry into the post-anesthesia care unit (PACU) to 48 hours after THA surgery

Secondary Outcomes (19)

• NRS (current at rest, with ambulation, worst & least in last 24 hours) Post-Operative Day (POD) 1-14

  From admission to the Post Anesthesia Care Unit (PACU) through 14 days postoperatively (Post-Op Day 14)

• Numeric Rating Scale - post-anesthesia care unit: average, least, worst

  From arrival in PACU until discharge criteria are met (expected duration up to 2 hours postoperatively).

• Numeric Rating Scale @Post-Operative Day14, @week 6, @week 12 - average pain, worst & least: last 7 days; current

  From 14 days following surgery, 6 weeks from surgery and 12 weeks from surgery.

• Cumulative Opioid consumption (Oral morphine equivalents = OME): post-anesthesia care unit, 0-24hours, 0 to 168 hours (7 days postoperatively) 0-Post-Operative Day14

  from first time in PACU to 24hours after, then 168hours after, and to 14 days after

• Opioid-free patients through Post-Operative Day2 (0-48hrs), Post-Operative Day7 (0-168hrs), Post-Operative Day14 (0-day 14)

  From start of trial to post operative day 2, 7 and 14

Study Arms (2)

Placebo arm

PLACEBO COMPARATOR

Other: Placebo

Suzetrigine

EXPERIMENTAL

Drug: Suzetrigine

Interventions

Placebo OTHER

This will be a placebo drug.

Placebo arm

Suzetrigine DRUG

Suzetrigine is a new novel peripherally acting non-opioid pain medication recently approved by the FDA that exerts its analgesic effects by binding to the peripherally located Nav1.8 Sodium channel receptors present on peripheral nerves.

Suzetrigine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing primary TKA with participating surgeons
• Age 18 to 80 years old
• Planned Discharge to home
• Planned use of neuraxial anesthesia
• American Society of Anesthesiologist (ASA) Physical Status 1 - 3
• Patients undergoing primary unilateral TKA with participating surgeons

You may not qualify if:

• ASA greater than 3
• Chronic opioid use (daily MME of greater than 30 mg for at least 3 months and within 1 month of surgery)
• History of chronic pain syndromes or uncontrolled pain (i.e. complex regional pain syndrome, fibromyalgia, implanted spinal cord stimulator)
• History of QT prolongation
• Presence of automated implantable cardioverter defibrillator, pacemaker or cardiac resynchronization device
• Evidence of misuse, aberrant use, or addiction to alcohol or an illicitly used drug of abuse, or had a positive test for drugs of abuse
• Inability to comply with any component of the study protocol
• Younger than 18 or greater than 80 years old at the time of enrollment
• Patient already on Suzetrigine
• Allergy or contraindication to Suzetrigine or excipients (eg moderate to severe liver disease/Child Pugh B or C, use of strong CYP3 inhibitors or inducers)
• Contraindications to neuraxial anesthesia or any other part of the study protocol
• Participation in another investigational drug or device study
• Pregnancy
• Prior osteotomy of the operative knee
• Baseline knee flexion \<60°

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

MeSH Terms

Conditions

Agnosia; Pain

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Meghan Kirskey, MD

  Department of Anesthesiology, Critical Care & Pain Management at the Hospital for Special Surgery

  PRINCIPAL INVESTIGATOR

• Alexandra Sideris, PhD

  Department of Anesthesiology, Critical Care & Pain Management at the Hospital for Special Surgery

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Curtis Weh, B.S.

CONTACT

917-260-3937; wehc@hss.edu

Hannah Gerner, MD

CONTACT

646-714-6509; Gernerha@hss.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2026
• First Posted: October 8, 2026
• Study Start: October 7, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: October 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)