Precision Pain Management - A Randomized Clinical Trial Assessing the Efficacy of Suzetrigine on Postoperative Analgesia Among Surgical Patients at Higher Risk for Persistent Postoperative Opioid Use (POU)

NCT07672015 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 814697
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate the efficacy of suzetrigine for treatment of acute postoperative pain among surgical patients identified as high risk for persistent postoperative opioid use (POU). Using a validated artificial intelligence predictive model (termed SurgNet-POU) developed by the PI, electronic health record (EHR) data will be queried from all prospective surgical patients undergoing orthopedic surgery and inputted into the model to predict risk of POU (defined as requiring opioids ≥ 3 months after surgery). Those identified as high risk by the SurgNet-POU will be eligible candidates for this study. Suzetrigine (Vertex Pharmaceuticals) is an FDA-approved non-opioid oral analgesic that acts as a selective Nav1.8 sodium channel blocker. It has been shown to have efficacy in post-surgical pain and has compared favorably to placebo and similar to some opioids, without the risk of addiction or other adverse events related to opioids. Consented participants will be randomized to one of two arms: (1) standard care (termed standard care) defined as usual prescribing outpatient opioid analgesic protocols per surgical team; versus (2) standard care combined with 14-day regimen of suzetrigine. Those randomized to the suzetrigine arm will receive 100mg suzetrigine PO \~ 1-2 hours prior to surgery and take 50mg po twice a day for 14 days postoperatively. The primary outcome will be total opioid consumption over 14 days postoperatively. Secondary outcomes include average, highest and lowest pain scores at 7, 14, 30, and 90 days after surgery; and opioid consumption at 7, 30, and 90 days after surgery.

Conditions

Opioid Consumption, Postoperative

Keywords

persistent postoperative opioid use; artificial intelligence; postoperative pain

Outcome Measures

Primary Outcomes (1)

• Total Opioid Consumption Over 14 Days Postoperatively

  Primary endpoint - total opioid consumption over the first 14 postoperative days (standardized to oral morphine equivalents in milligrams)

  From enrollment to 14 days postoperatively

Secondary Outcomes (4)

• Opioid Consumption Over Last 7 Days

  From enrollment to 3 months after surgery.

• Incidence of Persistent Opioid Use (POU)

  From enrollment to 3 months after surgery.

• Average, Worst, and Best Pain Over Last 7 Days

  From enrollment to 3 months after surgery.

• opioid-related side effects

  1 week, 14 days, 1 month, and 3 months after surgery

Study Arms (2)

Suzetrigine + Standard Care (standard outpatient analgesic prescriptions per surgical team)

EXPERIMENTAL

Suzetrigine is a selective sodium channel blocker, specifically targeting the Nav1.8 sodium channel found in peripheral pain-sensing nerves. Suzetrigine has been FDA approved for acute pain management for moderate-to-severe acute pain (e.g., post-surgical pain) and represents the first new class of pain medication in decades. Compared to opioids, there is no risk of respiratory depression, no associated euphoria (thus lower addiction risk), and does not act on the opioid receptors. Compared to NSAIDs, it has no kidney or GI bleeding risk or effects on the platelets. For participants randomized to this arm, they will receive 100mg po once preoperatively (approximately 1 - 2 hours prior to surgery) in the preoperative holding area. They will then receive 14 days 50mg po twice a day (first dose to start the evening of postoperative day 0. In addition, the participants will receive standard outpatient analgesic prescribing per their surgical provider.

Drug: Suzetrigine

Standard Care Alone

ACTIVE COMPARATOR

Participants in this group will receive standard outpatient analgesic prescribing (combination of opioids, NSAIDs, acetaminophen) per their surgical provider. No placebo pill will be administered.

Drug: Standard Care (in control arm)

Interventions

Suzetrigine DRUG

In addition to standard postoperative analgesia care (per surgeon), the participant in the intervention arm will receive a 14-day dosing regimen for suzetrigine.

Also known as: Journavx

Suzetrigine + Standard Care (standard outpatient analgesic prescriptions per surgical team)

Standard Care (in control arm) DRUG

participants will receive the standard postoperative analgesia care provided by their surgeon.

Standard Care Alone

Eligibility Criteria

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

You may qualify if:

• Patients who are identified as high-risk for POU as calculated by our SurgNet-POU predictive deep learning model. The probability threshold will be set at \~\> 0.25. Potential participants will be screened prior to surgery by incorporating their electronic health record data in to the model.
• Patients undergoing major orthopedic surgery (hip arthroplasty, knee arthroplasty, shoulder arthroplasty, joint arthroscopy, foot/ankle surgery, upper extremity fracture surgery, spine surgery), breast surgery (mastectomy, breast reconstruction), gynecological surgery (hysterectomy, myomectomy), or abdominal surgery.
• Adult patients of at least 18 years of age
• Has the capacity to consent

You may not qualify if:

• Pregnancy
• Incarceration
• Patients with a previous history of opioid use disorder.
• Patients on fentanyl transdermal patch, methadone, and/or buprenorphine.

Sponsors & Collaborators

• University of California, San Diego: lead
• Wellcome Leap Inc.: collaborator

Study Sites (1)

University of California, San Diego

La Jolla, California, 92037, United States

RECRUITING

Related Publications (3)

• Jones J, Correll DJ, Lechner SM, Jazic I, Miao X, Shaw D, Simard C, Osteen JD, Hare B, Beaton A, Bertoch T, Buvanendran A, Habib AS, Pizzi LJ, Pollak RA, Weiner SG, Bozic C, Negulescu P, White PF; VX21-548-101 and VX21-548-102 Trial Groups. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. N Engl J Med. 2023 Aug 3;389(5):393-405. doi: 10.1056/NEJMoa2209870.

  PMID: 37530822 BACKGROUND

• McCoun J, Winkle P, Solanki D, Urban J, Bertoch T, Oswald J, Swisher MW, Taber LA, Healey T, Jazic I, Correll DJ, Negulescu PA, Bozic C, Weiner SG; VX-548-107 Study Team. Suzetrigine, a Non-Opioid NaV1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain. J Pain Res. 2025 Mar 25;18:1569-1576. doi: 10.2147/JPR.S509144. eCollection 2025.

  PMID: 40165940 BACKGROUND

• Bertoch T, D'Aunno D, McCoun J, Solanki D, Taber L, Urban J, Oswald J, Swisher MW, Tian S, Miao X, Correll DJ, Negulescu P, Bozic C, Weiner SG. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025 Jun 1;142(6):1085-1099. doi: 10.1097/ALN.0000000000005460. Epub 2025 Mar 21.

  PMID: 40117446 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Rodney A Gabriel, MD, MAS

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rodney A Gabriel

CONTACT

858-663-7747; ragabriel@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start: July 2, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 6, 2026

Record last verified: 2026-06

Locations

US (1)