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

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.

• Suzetrigine (Drug): 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
• Opioid Analgesics (Tramadol or Oxycodone) (Drug): 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
• Scheduled Acetaminophen and Ibuprofen (Drug): 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.

Primary outcomes

• Pain intensity (0-10 NRS) at 48 hours postoperatively [48 hours postoperatively]: Patient-reported postoperative pain intensity measured using the 0-10 Numerical Rating Scale (NRS).

Secondary outcomes

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

Sex: Female, ages: 18 Years to any

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.

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• A Lenore Ackeman, MD, PhD, Principal investigator, University of California, Los Angeles