Precision Pain Management - A Randomized Clinical Trial Assessing the Efficacy of Suzetrigine on Postoperative Analgesia Among Surgical Patients at Higher Risk for Persistent Postoperative Opioid Use (POU)

The purpose of the study is to investigate the efficacy of suzetrigine for treatment ofacute postoperative pain among surgical patients identified as high risk for persistentpostoperative opioid use (POU). Using a validated artificial intelligence predictivemodel (termed SurgNet‐POU) developed by the PI, electronic health record (EHR) data willbe queried from all prospective surgical patients undergoing orthopedic surgery andinputted into the model to predict risk of POU (defined as requiring opioids ≥ 3 monthsafter surgery). Those identified as high risk by the SurgNet‐POU will be eligiblecandidates for this study. Suzetrigine (Vertex Pharmaceuticals) is an FDA‐approvednon‐opioid oral analgesic that acts as a selective Nav1.8 sodium channel blocker. It hasbeen shown to have efficacy in post‐surgical pain and has compared favorably to placeboand similar to some opioids, without the risk of addiction or other adverse eventsrelated to opioids. Consented participants will be randomized to one of two arms: (1)standard care (termed standard care) defined as usual prescribing outpatient opioidanalgesic protocols per surgical team; versus (2) standard care combined with 14‐dayregimen of suzetrigine. Those randomized to the suzetrigine arm will receive 100mgsuzetrigine PO 1‐2 hours prior to surgery and take 50mg po twice a day for 14 dayspostoperatively. The primary outcome will be total opioid consumption over 14 dayspostoperatively. Secondary outcomes include average, highest and lowest pain scores at 7,14, 30, and 90 days after surgery; and opioid consumption at 7, 30, and 90 days aftersurgery.Our objective is to investigate the therapeutic benefits of suzetrigine for postoperativeanalgesia among patients identified as high risk for POU from our AI model, SurgNet‐POU.Primary Specific Aim. Demonstrate the potential efficacy of suzetrigine for postoperativeanalgesia in patients undergoing major surgery that are identified as high risk for POU.This will be performed as a pilot study and executed as a randomized clinical trial of upto 100 participants.Hypothesis 1: Use of suzetrigine as part of a postoperative outpatient oral regimen willreduce 14‐day postoperative opioid consumption in patients that are higher risk for POU.Secondary Specific Aim: Among patients that are identified as high risk for POU aftersurgery, demonstrate the potential efficacy of suzetrigine in reducing pain and POUincidence after 3 months.Hypothesis 1: Pain and opioid consumption will be reduced in the suzetrigine groupcompare to control at multiple post‐procedure time points, including 1 week, 14 days, 1month, and 3 months after.There will be up to 100 participants recruited who are considered high risk for POU andundergoing major orthopedic surgery (hip arthroplasty, knee arthroplasty, shoulderarthroplasty, joint arthroscopy, foot/ankle surgery, upper extremity fracture surgery,spine surgery), breast surgery (mastectomy, breast reconstruction), gynecological surgery(hysterectomy, myomectomy), or abdominal surgery.