title: Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery.
abstract: In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery.
  
  
  
  Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships.
  
  
  
  Ethical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions. Trial results will be disseminated through scientific conference presentations and by publication in scientific journals.
  
  
  
  NCT02489526; pre-results.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Srdjan S
authors.initials: SS
authors.lastname: Nedeljkovic
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Correll
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Zamor
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Zeballos
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Young
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ledley
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Sorace
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Eng
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Carlyle P
authors.initials: CP
authors.lastname: Hamsher
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Rajivan
authors.initials: R
authors.lastname: Maniam
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Chin
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Becky
authors.initials: B
authors.lastname: Tsui
authors.affiliation: Vivozon, Inc. Seoul, Seoul, South Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Cho
authors.affiliation: Vivozon, Inc. Seoul, Seoul, South Korea.
authors.forename: Doo H
authors.initials: DH
authors.lastname: Lee
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000700:Analgesics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D003106:Colon / Q000601:surgery; D013505:Digestive System Surgical Procedures / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000627:therapeutic use; D010535:Laparoscopy / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000517:prevention & control*; D011446:Prospective Studies; D012007:Rectum / Q000601:surgery; D012107:Research Design; D055815:Young Adult
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004091:Hydromorphone
keywords: CLINICAL PHARMACOLOGY; PAIN MANAGEMENT