• Srdjan S Nedeljkovic, Inkyung Song, Xiaodong Bao, Jose L Zeballos, Darin J Correll, Yi Zhang, Johanna S Ledley, Ashish Bhandari, Xiang Bai, Sang Rim Lee, and Sunyoung Cho.
• Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: snedeljkovic@partners.org.
• J Clin Anesth. 2022 Feb 1; 76: 110576.

Study ObjectiveVVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery.DesignRandomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526).Setting3 academic institutions in the United States.Patients60 patients undergoing laparoscopic colorectal surgery.InterventionsA continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia.MeasurementsThe outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids.Main ResultsPostoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group.ConclusionsVVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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