The purpose of the study is to investigate the efficacy of suzetrigine for treatment of acute postoperative pain among surgical patients identified as high risk for persistent postoperative opioid use (POU). Using a validated artificial intelligence predictive model (termed SurgNet-POU) developed by the PI, electronic health record (EHR) data will be queried from all prospective surgical patients undergoing orthopedic surgery and inputted into the model to predict risk of POU (defined as requiring opioids ≥ 3 months after surgery). Those identified as high risk by the SurgNet-POU will be eligible candidates for this study. Suzetrigine (Vertex Pharmaceuticals) is an FDA-approved non-opioid oral analgesic that acts as a selective Nav1.8 sodium channel blocker. It has been shown to have efficacy in post-surgical pain and has compared favorably to placebo and similar to some opioids, without the risk of addiction or other adverse events related to opioids. Consented participants will be randomized to one of two arms: (1) standard care (termed standard care) defined as usual prescribing outpatient opioid analgesic protocols per surgical team; versus (2) standard care combined with 14-day regimen of suzetrigine. Those randomized to the suzetrigine arm will receive 100mg suzetrigine PO ~ 1-2 hours prior to surgery and take 50mg po twice a day for 14 days postoperatively. The primary outcome will be total opioid consumption over 14 days postoperatively. 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 after surgery.

The purpose of the study is to investigate the efficacy of suzetrigine for treatment of acute postoperative pain among surgical patients identified as high risk for persistent postoperative opioid use (POU). Using a validated artificial intelligence predictive model (termed SurgNet-POU) developed by the PI, electronic health record (EHR) data will be queried from all prospective surgical patients undergoing orthopedic surgery and inputted into the model to predict risk of POU (defined as requiring opioids ≥ 3 months after surgery). Those identified as high risk by the SurgNet-POU will be eligible candidates for this study. Suzetrigine (Vertex Pharmaceuticals) is an FDA-approved non-opioid oral analgesic that acts as a selective Nav1.8 sodium channel blocker. It has been shown to have efficacy in post-surgical pain and has compared favorably to placebo and similar to some opioids, without the risk of addiction or other adverse events related to opioids. Consented participants will be randomized to one of two arms: (1) standard care (termed standard care) defined as usual prescribing outpatient opioid analgesic protocols per surgical team; versus (2) standard care combined with 14-day regimen of suzetrigine. Those randomized to the suzetrigine arm will receive 100mg suzetrigine PO ~ 1-2 hours prior to surgery and take 50mg po twice a day for 14 days postoperatively. The primary outcome will be total opioid consumption over 14 days postoperatively. 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 after surgery.

Our objective is to investigate the therapeutic benefits of suzetrigine for postoperative analgesia among patients identified as high risk for POU from our AI model, SurgNet-POU.

Primary Specific Aim. Demonstrate the potential efficacy of suzetrigine for postoperative analgesia 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 up to 100 participants.

Hypothesis 1: Use of suzetrigine as part of a postoperative outpatient oral regimen will reduce 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 after surgery, demonstrate the potential efficacy of suzetrigine in reducing pain and POU incidence after 3 months.

Hypothesis 1: Pain and opioid consumption will be reduced in the suzetrigine group compare to control at multiple post-procedure time points, including 1 week, 14 days, 1 month, and 3 months after.

There will be up to 100 participants recruited who are considered high risk for POU and undergoing major orthopedic surgery (hip arthroplasty, knee arthroplasty, shoulder arthroplasty, joint arthroscopy, foot/ankle surgery, upper extremity fracture surgery, spine surgery), breast surgery (mastectomy, breast reconstruction), gynecological surgery (hysterectomy, myomectomy), or abdominal surgery.

Inclusion Criteria:

• Patients who are identified as high-risk for POU as calculated by our SurgNet-POU predictive deep learning model. The probability threshold will be set at ~> 0.25. Potential participants will be screened prior to surgery by incorporating their electronic health record data in to the model.
• Patients undergoing major orthopedic surgery (hip arthroplasty, knee arthroplasty, shoulder arthroplasty, joint arthroscopy, foot/ankle surgery, upper extremity fracture surgery, spine surgery), breast surgery (mastectomy, breast reconstruction), gynecological surgery (hysterectomy, myomectomy), or abdominal surgery.
• Adult patients of at least 18 years of age
• Has the capacity to consent

Exclusion Criteria:

• Pregnancy
• Incarceration
• Patients with a previous history of opioid use disorder.
• Patients on fentanyl transdermal patch, methadone, and/or buprenorphine.

due to HIPAA regulations