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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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
• Препарат 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
• Препарат 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.

Первичные конечные точки

• Pain intensity (0-10 NRS) at 48 hours postoperatively [Срок оценки: 48 hours postoperatively]

Вторичные конечные точки (10)

• Pain Intensity at 1 Week [Срок оценки: 1 week after surgery]
• Time to Rescue Analgesia in PACU [Срок оценки: During stay in post-anesthesia care unit, measured in hours up to 23 hours]
• Post-Discharge Opioid Use [Срок оценки: Postoperative days 0-7]
• Post-Discharge Gabapentin Use [Срок оценки: Postoperative days 0-7]
• Constipation [Срок оценки: Up to 1 week postoperatively]
• Nausea and Vomiting [Срок оценки: Up to 1 week postoperatively]
• Dizziness or Lightheadedness [Срок оценки: Up to 1 week postoperatively]
• Time to Return to Driving [Срок оценки: Up to 6 weeks]
• Time to Return to Work [Срок оценки: Up to 6 weeks]
• Postoperative Patient-Initiated Communication Burden [Срок оценки: Up to 6 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California, Los Angeles (UCLA) — Los Angeles

Публикации

• 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. PMID 27392806
• 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. PMID 17382829
• 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. PMID 31201808
• Keam SJ. Suzetrigine: First Approval. Drugs. 2025 Jun;85(6):845-851. doi: 10.1007/s40265-025-02178-w. Epub 2025 May 5. PMID 40323340
• 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. PMID 41233910
• 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. PMID 40424150

Идентификаторы

NCT: NCT07600697 · 26-0498

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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