A non-opioid analgesic strategy for enhanced recovery after total knee arthroplasty: study protocol for the SUTKA randomized double-blind, placebo-controlled trial of suzetrigine

Pain after total knee arthroplasty (TKA) remains difficult to control, and most patients still require opioids two weeks after surgery despite multimodal enhanced recovery after surgery (ERAS) protocols, exposing patients to opioid-related complications and persistent use. Suzetrigine is a first-in-class, orally administered, selective NaV1.8 sodium-channel inhibitor approved for moderate-to-severe acute pain that provides analgesia without sedation, respiratory depression, or dependence. The objective is to determine whether adding suzetrigine to standardized multimodal analgesia reduces opioid consumption after primary unilateral TKA. This single-center, prospective, randomized, double-blind, placebo-controlled superiority trial will enroll 154 patients randomized 1:1, stratified by age and sex. The intervention group receives a preoperative loading dose of suzetrigine 100 mg orally in the holding area, then 50 mg orally twice daily for 14 days; the control group receives volume-matched placebo on the same schedule. All patients receive standardized multimodal analgesia. The primary outcome is cumulative opioid consumption in oral morphine milligram equivalents (MME) over 14 days; secondary outcomes include pain intensity, range of motion, length of stay, and patient-reported outcomes. Analyses will follow the intention-to-treat principle. This study is designed to provide high-level (Level I) evidence on the role of suzetrigine in opioid-sparing recovery after TKA.Clinical trial registration The https://clinicaltrials.gov identifier is NCT07357376.