title: Pilot, randomized, placebo-controlled clinical field study to evaluate the effectiveness of bupivacaine liposome injectable suspension for the provision of post-surgical analgesia in dogs undergoing stifle surgery.
abstract: BACKGROUND
  Local anesthetics are an important component of perioperative pain management, but the duration of action of available products is limited. We hypothesized that a single local infiltration of a novel bupivacaine liposome injectable suspension (AT-003) would provide clinically effective analgesia over a 72-h period. In a masked, randomized, placebo-controlled, multi-center pilot field study, dogs undergoing lateral retinacular suture placement for cranial cruciate insufficiency were randomly assigned to surgical site infiltration with AT-003 (5.3 mg/kg) or an equivalent volume of saline. Infiltration of the surgical site was done prior to closure. Primary outcome measure was the Glasgow Composite Measure Pain Scale (CMPS-SF) assessed prior to surgery and at 2, 4, 8, 12, 24, 30, 36, 48, 54, 60 and 72 h following surgery by trained individuals. Provision for rescue analgesia was employed. Repeated measures analysis of variance were utilized to test for possible differences between treatment groups and a success/failure analysis was also employed, based on the need for rescue analgesia.
  
  
  RESULTS
  Forty-six dogs were enrolled and evaluated. For CMPS-SF scores there was a significant overall treatment effect (p = 0.0027) in favor of AT-003. There were significantly more successes in the AT-003 group compared to placebo over each time period (p = 0.0001 for 0-24 h, p = 0.0349 for 0-48 h, and p = 0.0240 for 0-72 h). No significant adverse events were seen.
  
  
  CONCLUSIONS
  AT-003 (bupivacaine liposome injectable suspension) provided measurable local analgesia over a 72-h period following post-stifle surgery surgical site tissue infiltration. Further work is indicated to develop this product for clinical use.
authors.affiliation: Department of Clinical Sciences, Comparative Pain Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. duncan_lascelles@ncsu.edu.|Department of Clinical Sciences, Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA. duncan_lascelles@ncsu.edu.|Center for Pain Research and Innovation, Dental School, UNC Chapel Hill, Chapel Hill, NC, USA. duncan_lascelles@ncsu.edu.|Department of Anesthesiiology, Center for Translational Pain Medicine, Duke University, Durham, NC, USA. duncan_lascelles@ncsu.edu.
authors.forename: B Duncan X
authors.initials: BD
authors.lastname: Lascelles
authors.affiliation: Aratana Therapeutics, Inc., Leawood, KS, 66211, USA.
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Rausch-Derra
authors.affiliation: Aratana Therapeutics, Inc., Leawood, KS, 66211, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Wofford
authors.affiliation: ClinData Services, Inc., 6716 Holyoke Court, Fort Collins, CO, 80525, USA.
authors.forename: Margie
authors.initials: M
authors.lastname: Huebner
mesh_terms: D000698:Analgesia / Q000662:veterinary*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D004283:Dog Diseases / Q000601:surgery*; D004285:Dogs; D005260:Female; D008081:Liposomes; D008297:Male; D010149:Postoperative Pain / Q000517:prevention & control / Q000662:veterinary*; D010865:Pilot Projects; D013264:Stifle / Q000601:surgery*
chemical_list: D000779:Anesthetics, Local; D008081:Liposomes; D002045:Bupivacaine
keywords: Bupivacaine liposome injectable suspension; Cruciate surgery; Dog; Pain