A Pilot Randomized Controlled Trial of Suzetrigine as an Adjunct to Multimodal Analgesia Following Total Knee Arthroplasty

This proposal seeks to determine if the addition of Suzetrigine, a novel non-opioid pain medication, to a standardized multimodal pain management pathway significantly reduces total postoperative opioid consumption (measured in Morphine Milligram Equivalents [MME]) and improves patient-reported pain scores during the first 14 days following primary total knee arthroplasty (TKA). Prior to conducting a definitive randomized control trial (RCT), we propose a pilot study to inform the trial's design and feasibility.

Objective: To inform the design and feasibility of a definitive RCT comparing postoperative pain control with and without Suzetrigine after TKA. To achieve this objective, we will conduct a pilot trial and address the following aims:

1) to determine if participant enrollment is feasible, 2) to assess compliance with treatment protocol and key aspects of the protocol, and 3) to refine data collection methods.

Study Overview

• Status: Not yet recruiting
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: Suzetrigine

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Peter Hsiue, MD; Phone Number: 714-456-7012; Email: phsiue@hs.uci.edu
• Study Contact Backup: Name: Steven Yang, MD; Phone Number: 714-456-7012; Email: stevey1@hs.uci.edu

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UCI Health Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 18 to 80 years
• Diagnosis of knee osteoarthritis
• Scheduled for unilateral TKA
• Willingness to maintain a 14-day medication and pain log

Exclusion Criteria:

• Chronic opioid use
• Severe renal impairment (eGFR < 30 mL/min) or severe hepatic impairment (Child-Pugh Class C)
• History of active peptic ulcer disease or GI bleeding
• Known allergies to any of the study medications (suzetrigine, acetaminophen, meloxicam, or oxycodone).
• Significant peripheral neuropathy in the operative extremity
• Active history of substance abuse or opioid use disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Multimodal Group; Standard multimodal control group will receive treatment components such as nerve block through an adductor canal catheter for 4 days, cryotherapy/icing as needed, scheduled non-opioid drug (acetaminophen 1000 mg 3 times a day), nonsteroidal anti-inflammatory drug (NSAID) (Meloxicam 15mg daily), and breakthrough opioid (Oxycodone 5mg every 4 hours as needed).
Experimental: Suzetrigine Group; The Suzetrigine group will receive a 100 mg loading dose of Suzetrigine, followed by 50mg Q12h for 14 days as an addition to a standardized multimodal pain management pathway. The standardized multimodal pain management pathway consists of treatment components such as nerve block through an adductor canal catheter for 4 days, cryotherapy/icing as needed, scheduled non-opioid drug (acetaminophen 1000 mg 3 times a day), nonsteroidal anti-inflammatory drug (NSAID) (Meloxicam 15mg daily), and breakthrough opioid (Oxycodone 5mg every 4 hours as needed).	Drug: Suzetrigine; 100 mg loading dose of Suzetrigine, followed by 50mg every 12 hours for 14 days as an addition to a standardized multimodal pain management pathway.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant enrollment	Enrollment rates	At enrollment
Protocol adherence	Protocol adherence rates	Within 14 days
Data collection	Completeness of data collection	At 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Clinical Outcome: Opioid consumption	Total cumulative opioid consumption in milligrams morphine equivalents (MME) within the study period	Within 14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain	Numeric Pain Rating Scale (NPRS): Zero is equivalent to no pain and 10 indicates the worst possible pain.	At 14 days
First day of walking unassisted		Within 14 days
Barthel Index for Activities of Daily Living (ADL)	Cumulative score ranges from 0 to 100, where 0 indicates complete dependence and 100 signifies total independence	At 14 days
Knee injury and Osteoarthritis Outcome Score (KOOS)	0 represents extreme knee problems, and 100 represents no knee problems	At 14 days
Knee range of motion	Clinical assessment	At 14 days
Time to opioid cessation		Within 14 days
Opioid prescription renewal		Within 14 days
Incidence of opioid-related adverse events		Within 14 days

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Investigators: Principal Investigator: Peter Hsiue, MD, University of California, Irvine; Principal Investigator: Steven Yang, MD, University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: October 1, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 10, 2026

Study Record Updates

• Last Update Posted (Actual): November 10, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: STUDY00001001

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.: Yes