Summary
Total knee replacements are among the most common and painful orthopedic procedures performed worldwide, often requiring intensive analgesia to support early ambulation and recovery. Despite widespread use of multimodal regimens, many patients still rely on opioids, which can cause sedation, nausea, constipation, and long-term dependency. Evaluating suzetrigine in this high-need population may improve recovery trajectories, reduce opioid consumption, and support enhanced recovery protocols. Given the growing surgical volume and the emphasis on opioid-sparing strategies, rigorous investigation of suzetrigine's efficacy in total knee replacement is of high clinical value. In this confirmatory (phase III) trial, patients undergoing primary total knee replacement will be randomized to receive either suzetrigine or placebo for 2 weeks (14 days), with the loading dose administered prior to surgery. The primary outcome is cumulative 48-hour opioid consumption in oral morphine equivalents starting from entry into the post-anesthesia care unit (PACU).
Eligibility Criteria
Age Range: 18 years to 80 years
Inclusion Criteria:
* Patients undergoing primary TKA with participating surgeons
* Age 18 to 80 years old
* Planned Discharge to home
* Planned use of neuraxial anesthesia
* American Society of Anesthesiologist (ASA) Physical Status 1 - 3
* Patients undergoing primary unilateral TKA with participating surgeons
Exclusion Criteria:
* ASA greater than 3
* Chronic opioid use (daily MME of greater than 30 mg for at least 3 months and within 1 month of surgery)
* History of chronic pain syndromes or uncontrolled pain (i.e. complex regional pain syndrome, fibromyalgia, implanted spinal cord stimulator)
* History of QT prolongation
* Presence of automated implantable cardioverter defibrillator, pacemaker or cardiac resynchronization device
* Evidence of misuse, aberrant use, or addiction to alcohol or an illicitly used drug of abuse, or had a positive test for drugs of abuse
* Inability to comply with any component of the study protocol
* Younger than 18 or greater than 80 years old at the time of enrollment
* Patient already on Suzetrigine
* Allergy or contraindication to Suzetrigine or excipients (eg moderate to severe liver disease/Child Pugh B or C, use of strong CYP3 inhibitors or inducers)
* Contraindications to neuraxial anesthesia or any other part of the study protocol
* Participation in another investigational drug or device study
* Pregnancy
* Prior osteotomy of the operative knee
* Baseline knee flexion \<60°
* History of infection or septic arthritis of the operative knee