Suzetrigine for Opioid-Sparing Postoperative Analgesia Following Transvaginal Pelvic Reconstructive Surgery

Suzetrigine is a selective NaV1.8 inhibitor that provides peripheral analgesia without opioid-related CNS effects. This single-center stepped-wedge randomized clinical trial evaluates whether a suzetrigine-based postoperative analgesic regimen provides non-inferior pain control compared with standard opioid-inclusive care following transvaginal pelvic reconstructive surgery. The study will enroll 120 participants and assess pain, opioid consumption, adverse events, and functional recovery.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Pain; Pelvic Organ Prolapse (POP); Stress Urinary Incontinence (SUI)
• Intervention / Treatment: Drug: Suzetrigine; Drug: Scheduled Acetaminophen and Ibuprofen; Drug: Opioid Analgesics (Tramadol or Oxycodone)

Detailed Description

Suzetrigine has demonstrated analgesic efficacy comparable to hydrocodone/acetaminophen in Phase III trials and is FDA-approved for acute pain. This trial represents the first evaluation of a NaV1.8 inhibitor in pelvic reconstructive surgery. Participants will receive either suzetrigine or standard opioid-inclusive postoperative care according to a stepped-wedge randomization schedule. Pain scores, medication use, and adverse events will be collected at 48 hours, 1 week, and 6 weeks postoperatively.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: A Lenore Ackerman, MD, PhD; Phone Number: 310-794-0206; Email: aackerman@mednet.ucla.edu
• Study Contact Backup: Name: Cindy Gu, MD; Phone Number: 35879 310-794-7700; Email: cgu@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles (UCLA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Undergoing elective transvaginal pelvic reconstructive surgery at UCLA with planned same-day discharge or 23-hour observation.
• Able to provide written informed consent.

Exclusion Criteria:

• Chronic opioid use.
• Liver failure.
• End-stage renal disease (ESRD).
• Chronic pain syndromes, including:

Fibromyalgia Interstitial cystitis Chronic pelvic pain

• Contraindication to acetaminophen or ibuprofen.
• Use of strong CYP3A4 inhibitors within 7 days prior to surgery or anticipated need during the treatment period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Suzetrigine-Based Regimen; Participants receive suzetrigine as part of a multimodal postoperative analgesic regimen. Suzetrigine is administered as a loading dose on the morning of surgery followed by twice-daily dosing for 7 days, in combination with scheduled acetaminophen and ibuprofen.	Drug: Suzetrigine; Loading dose: 100 mg orally on the morning of surgery Maintenance dose: 50 mg orally every 12 hours for 7 days Co-administered medications: Scheduled acetaminophen and ibuprofen Mechanism: Selective NaV1.8 sodium channel inhibitor acting on peripheral nociceptive neurons Purpose: Opioid-sparing postoperative analgesia; Drug: Scheduled Acetaminophen and Ibuprofen; Participants in both study arms will receive scheduled acetaminophen and ibuprofen as part of standard multimodal postoperative analgesia. These medications are administered routinely following transvaginal pelvic reconstructive surgery to reduce baseline pain, minimize opioid requirements, and support enhanced recovery.
Active Comparator: Standard Opioid-Inclusive Analgesic Regimen; Participants receive standard postoperative pain management consisting of scheduled acetaminophen and ibuprofen, with opioid analgesics available as needed per routine clinical care.	Drug: Scheduled Acetaminophen and Ibuprofen; Participants in both study arms will receive scheduled acetaminophen and ibuprofen as part of standard multimodal postoperative analgesia. These medications are administered routinely following transvaginal pelvic reconstructive surgery to reduce baseline pain, minimize opioid requirements, and support enhanced recovery.; Drug: Opioid Analgesics (Tramadol or Oxycodone); Tramadol: 50 mg orally every 4-6 hours as needed OR Oxycodone: 5 mg orally every 4-6 hours as needed Co-administered medications: Scheduled acetaminophen and ibuprofen Purpose: Standard postoperative analgesia per institutional protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity (0-10 NRS) at 48 hours postoperatively	Patient-reported postoperative pain intensity measured using the 0-10 Numerical Rating Scale (NRS).	48 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity at 1 Week	Patient-reported pain intensity using the 0-10 NRS.	1 week after surgery
Time to Rescue Analgesia in PACU	Time from arrival in the post-anesthesia care unit to first administration of rescue analgesic medication.	During stay in post-anesthesia care unit, measured in hours up to 23 hours
Post-Discharge Opioid Use	Total opioid consumption after discharge, measured in morphine milligram equivalents (MME).	Postoperative days 0-7
Post-Discharge Gabapentin Use	Any gabapentin or pregabalin use after discharge.	Postoperative days 0-7
Constipation	Time to first bowel movement Additional bowel regimen use	Up to 1 week postoperatively
Nausea and Vomiting	Incidence of postoperative nausea or vomiting reported by participants.	Up to 1 week postoperatively
Dizziness or Lightheadedness	Incidence of postoperative dizziness or lightheadedness.	Up to 1 week postoperatively
Time to Return to Driving	Number of days from surgery until the participant reports resuming driving.	Up to 6 weeks
Time to Return to Work	Number of days from surgery until the participant reports returning to work.	Up to 6 weeks
Postoperative Patient-Initiated Communication Burden	Number of patient-initiated messages, calls, or portal contacts related to postoperative pain or medication concerns.	Up to 6 weeks

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: A Lenore Ackeman, MD, PhD, University of California, Los Angeles

Publications and helpful links

General Publications

• Dong S, Zhong Y, Chu L, Li H, Tong X, Wang J. Age-stratified analysis of long-term outcomes of transvaginal mesh repair for treatment of pelvic organ prolapse. Int J Gynaecol Obstet. 2016 Oct;135(1):112-6. doi: 10.1016/j.ijgo.2016.03.031. Epub 2016 Jun 20.
• Jelovsek JE, Maher C, Barber MD. Pelvic organ prolapse. Lancet. 2007 Mar 24;369(9566):1027-38. doi: 10.1016/S0140-6736(07)60462-0.
• Petrikovets A, Sheyn D, Sun HH, Chapman GC, Mahajan ST, Pollard RR, El-Nashar SA, Hijaz AK, Mangel J. Multimodal opioid-sparing postoperative pain regimen compared with the standard postoperative pain regimen in vaginal pelvic reconstructive surgery: a multicenter randomized controlled trial. Am J Obstet Gynecol. 2019 Nov;221(5):511.e1-511.e10. doi: 10.1016/j.ajog.2019.06.002. Epub 2019 Jun 12.
• Keam SJ. Suzetrigine: First Approval. Drugs. 2025 Jun;85(6):845-851. doi: 10.1007/s40265-025-02178-w. Epub 2025 May 5.
• Ali MY, Antunes FTT, Huang S, Chen L, Zamponi GW. Pharmacological inhibition of NaV1.8 by suzetrigine reveals potent analgesic potential without tolerance development in mice. Mol Brain. 2025 Nov 13;18(1):86. doi: 10.1186/s13041-025-01253-3.
• Stewart RG, Osorno T, Fujita A, Jo S, Ferraiuolo A, Carlin K, Bean BP. Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine. Proc Natl Acad Sci U S A. 2025 Jun 3;122(22):e2503570122. doi: 10.1073/pnas.2503570122. Epub 2025 May 27.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 15, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: postoperative pain; randomized clinical trial; pelvic organ prolapse; transvaginal surgery; multimodal pain management; stepped-wedge design; pelvic reconstructive surgery; Suzetrigine; NaV1.8 Inhibitor; opioid-sparing analgesia; Non-opioid analgesic; phase 4 trial
• Additional Relevant MeSH Terms: Urogenital Diseases; Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Male Urogenital Diseases; Pathological Conditions, Anatomical; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Incontinence; Prolapse; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Urinary Incontinence, Stress; Pelvic Organ Prolapse; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Narcotics; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Lipids; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Carboxylic Acids; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Amines; Alcohols; Heterocyclic Compounds, 4 or More Rings; Acids, Carbocyclic; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Central Nervous System Agents; Morphine Derivatives; Codeine; Phenylpropionates; Cyclohexanols; Hexanols; Fatty Alcohols; Dimethylamines; Methylamines; Analgesics, Opioid; Tramadol; Ibuprofen; Oxycodone
• Other Study ID Numbers: 26-0498

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigators do not plan to share individual participant data (IPD). Due to the sensitive nature of postoperative clinical data and institutional policies regarding patient privacy, de-identified datasets will not be made available. Study findings will be disseminated through aggregate results posted on ClinicalTrials.gov and peer-reviewed publications.

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