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. The https://clinicaltrials.gov identifier is NCT07357376. Knee replacement is a common operation, but the pain afterward can be hard to control. Many people still need opioid pain medicine two weeks after surgery. Opioids can cause side effects such as nausea, constipation, drowsiness, and falls, and they carry a risk of dependence. Doctors would like patients to need fewer opioids while still being comfortable. Suzetrigine (sold as Journavx in the US) is a newer pain pill that is not an opioid. It blocks pain signals in the nerves and does not cause the same risks as opioids. This study will include 154 people having knee replacement surgery. Everyone will receive the same standard pain medicines. One group will also take suzetrigine for 14 days. The other group will take a placebo, an inactive pill that looks the same but contains no medicine. Patients will not know which one they are taking. We will measure how much opioid medicine each group uses, how much pain people report, how well the knee moves, and how patients feel about their recovery, before surgery and during follow-up visits. This study may help show whether suzetrigine is useful for lowering opioid use after knee replacement surgery.