Cesarean Delivery, Cesarean Section, Opioid Consumption, Postoperative, Pain, Postoperative
Conditions
Keywords
suzetrigine, Cesarean Delivery, cesarean section, postoperative pain, opioid-free recovery, opioid-sparing, multimodal analgesia, postpartum opioid use, NaV1.8 Inhibitor
Brief summary
The goal of this clinical trial is to determine whether suzetrigine increases the proportion of patients who remain completely opioid-free from completion of surgery through 72 hours after cesarean delivery. The main question it aims to answer is: Does adjunctive suzetrigine, when added to a standardized multimodal postoperative analgesic regimen, increase the proportion of patients who remain opioid-free during the first 72 hours after cesarean delivery? Researchers will compare suzetrigine to a placebo (a look-alike substance that contains no drug) to evaluate this outcome. Participants will: * Receive either suzetrigine or placebo after cesarean delivery * Receive standard postoperative pain management, including acetaminophen, nonsteroidal anti-inflammatory drugs, and neuraxial morphine * Have opioid medications available as needed for breakthrough pain * Be followed during hospitalization and after discharge to assess pain, recovery, and medication use
Detailed description
This is a single-site, randomized, double-blind, placebo-controlled clinical trial evaluating whether adjunctive suzetrigine increases the proportion of patients who remain opioid-free following cesarean delivery. The study is conducted at a tertiary care academic medical center. Participants undergoing cesarean delivery under neuraxial anesthesia are randomized in a 1:1 ratio to receive either oral suzetrigine or a matching placebo following surgery. Randomization is performed using a computer-generated sequence with permuted blocks of variable size and allocation concealment through a secure electronic system. Participants, clinicians, investigators, and study personnel are blinded to treatment assignment. The intervention consists of oral suzetrigine administered in the immediate postoperative period, beginning with a loading dose within 90 minutes after skin closure, followed by scheduled maintenance dosing every 12 hours. Participants randomized to the control arm receive a matching placebo on the same schedule. Study medication is prepared and dispensed by the investigational pharmacy in identical packaging to maintain blinding. All participants receive standardized multimodal postoperative analgesia consistent with institutional enhanced recovery pathways, including scheduled acetaminophen and non-steroidal anti-inflammatory drugs, as well as neuraxial morphine administered intraoperatively. Opioid medications remain available for breakthrough pain at the discretion of the clinical care team. Suzetrigine is a selective NaV1.8 voltage-gated sodium channel inhibitor that targets peripheral nociceptive pathways and does not act on opioid receptors. This study evaluates its use as an adjunct to standard multimodal analgesia in a postpartum surgical population in which opioid exposure remains common despite guideline-recommended care. Participants are followed during their inpatient hospitalization and through the early postpartum period using a combination of electronic medical record data and structured follow-up assessments to capture medication use, recovery, and patient-reported outcomes. Data are recorded using secure electronic data capture systems with predefined data fields and standardized collection procedures. Analyses will be conducted using an intention-to-treat approach, with comparisons between randomized groups based on pre-specified analytical methods appropriate for outcome type. Participant safety is monitored throughout the study period through routine clinical care, structured follow-up assessments, and oversight by an independent data safety monitoring board.
Interventions
DRUGSuzetrigine
Oral suzetrigine administered following cesarean delivery as an adjunct to standardized multimodal postoperative analgesia, including scheduled acetaminophen and nonsteroidal anti-inflammatory drugs, with opioid medications available as needed for breakthrough pain.
DRUGPlacebo
Matching oral placebo administered following cesarean delivery in addition to standardized multimodal postoperative analgesia, including scheduled acetaminophen and nonsteroidal anti-inflammatory drugs, with opioid medications available as needed for breakthrough pain.
Sponsors
University of Texas at Austin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
This study is double-blind, with participants and clinical care providers masked to treatment assignment.
Intervention model description
Participants will be randomized in a 1:1 ratio to one of two parallel groups (suzetrigine or placebo) for the duration of the study. Randomization will be performed using a computer-generated allocation sequence with variable block sizes and allocation concealment.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women aged ≥18 years. * Undergoing scheduled or unscheduled cesarean delivery during the current admission, with or without concomitant salpingectomy. * Planned delivery under neuraxial anesthesia (spinal, epidural, or combined spinal-epidural). * Planned Pfannenstiel skin incision. * Able to provide informed consent in English or Spanish. * Willing and able to complete required remote follow-up assessments through postoperative day 14 (POD14).
Exclusion criteria
* Planned provision of breast milk to the neonate during the period of suzetrigine exposure (while the study drug is being taken and for 96 hours after last dose), due to the absence of human lactation safety data for suzetrigine.\* * Known allergy, hypersensitivity, or contraindication to suzetrigine or any component of its formulation. * Chronic opioid use, defined as daily opioid use for more than 7 consecutive days in the month prior to delivery, or current treatment for opioid use disorder. * Significant hepatic disease, defined as AST or ALT \>3 times the upper limit of normal or Child-Pugh class B or C. * Severe renal impairment, defined as estimated glomerular filtration rate (eGFR) \<15 mL/min. * Concurrent use of medications known to significantly alter suzetrigine metabolism, including strong CYP3A inhibitors or inducers, such as: * ketoconazole * ritonavir * carbamazepine * rifampin * St. John's wort (or other agents deemed clinically significant CYP3A modulators by the study investigator team) * Planned cesarean delivery under general anesthesia without neuraxial anesthesia. * Planned non-Pfannenstiel skin incision (e.g., vertical midline incision). * Participation in another interventional pain-management clinical trial during the current hospitalization. * Additional operative procedures (excluding salpingectomy) performed at the time of cesarean delivery (e.g., hysterectomy, hernia repair). * Inability to provide informed consent or to complete required study procedures and follow-up. * Receipt of opioid or sedating medications prior to completion of the informed consent process. * Feeding decisions are made independently of study participation. The study does not require participants to alter infant feeding plans; eligibility is determined solely by whether breast milk will be provided to the neonate during the period of study drug exposure (while the study drug is being taken and for 96 hours after last dose). Participants who plan to breastfeed but independently elect not to provide breast milk to the neonate during the period of suzetrigine exposure are eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Remaining Opioid-Free Through 72 Hours Postoperatively | From completion of surgery to 72 hours postoperatively | Proportion of participants who do not receive any opioid medications from completion of cesarean delivery through 72 hours postoperatively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Pain Intensity Scores | During hospitalization through 72 hours postoperatively | Patient-reported pain intensity measured using the Numeric Rating Scale (NRS) for pain, an 11-point scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst possible pain. Higher scores represent greater pain intensity. |
| Maternal Satisfaction With Pain Management | At hospital discharge and postoperative day 14 | Participant-reported satisfaction with postoperative pain management assessed using a single-item Likert-type scale ranging from 0 to 10, where 0 indicates completely dissatisfied and 10 indicates completely satisfied. Higher scores indicate greater satisfaction. |
| Functional Recovery After Cesarean Delivery | Postoperative day 7 | Functional recovery assessed using the Obstetric Quality of Recovery-11 (ObsQoR-11) questionnaire, a validated 11-item patient-reported outcome measure evaluating multiple domains of postoperative recovery, including pain, physical comfort, functional independence, and ability to care for the newborn. Each item is scored on an 11-point numeric scale (0-10), with total scores ranging from 0 to 110. Higher scores indicate better overall recovery. |
| Post-Discharge Opioid Use | From hospital discharge through postoperative day 14 | Participant-reported opioid use after hospital discharge, including total quantity of opioid medications used, collected via structured self-report and expressed as number of tablets consumed or morphine milligram equivalents (MME) when available. |
| Study Drug Adherence (Proportion of Prescribed Study Medication Doses Taken) | During hospitalization through postoperative day 7 | Participant adherence to the assigned study medication regimen (suzetrigine or matching placebo), defined as the proportion of prescribed study medication doses taken during the postoperative period. Adherence will be calculated as the number of doses taken divided by the number of doses prescribed. For inpatient doses, adherence will be assessed using the electronic medication administration record (MAR). For postdischarge doses, adherence will be assessed using participant self-report with pill count verification when feasible. |
| Adverse Events | From study drug initiation through postoperative day 14 | Occurrence of adverse events during the study period, assessed through clinical evaluation, electronic medical record review, and participant-reported follow-up assessments. |
Countries
United States
Contacts
CONTACTChase Calvert, MD
STUDY_DIRECTORLorie M. Harper, MD, MSCI
Dell Medical School, University of Texas at Austin, Department of Women's Health
Outcome results
None listed