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      Evaluation of injectable robenacoxib for the treatment of post-operative pain in cats: results of a randomized, masked, placebo-controlled clinical trial

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          Abstract

          Background

          Few pharmaceuticals are registered in cats for the management of post-operative pain and inflammation. The objective of this study was to assess the field efficacy and safety of an injectable formulation of the nonsteroidal anti-inflammatory drug robenacoxib in cats undergoing surgery. The study was a multi-center, prospective, randomized, masked, parallel-group, placebo-controlled clinical trial. A total of 349 cats were enrolled and underwent surgery comprising forelimb onychectomy, as an example of orthopedic surgery, plus either ovariohysterectomy or castration. All cats received butorphanol prior to anesthesia and forelimb four-point regional nerve blocks with bupivacaine after induction of general anesthesia. Cats were randomized to receive daily subcutaneous (s.c.) injection of robenacoxib, at a target dosage of 2.0 mg/kg ( n = 174), or placebo ( n = 175) once prior to surgery and for an additional two days post-operatively.

          Results

          Significantly ( P = 0.037) fewer cats administered robenacoxib received additional analgesia rescue therapy (34 of 173, 19.7 %) compared to cats given placebo (73 of 175, 41.7 %). The percentage of treatment success was therefore 80.3 % with robenacoxib and 58.3 % with placebo. Behavior, posture, pain on palpation of the paw and soft tissue surgery sites, and overall pain were significantly ( P < 0.05) improved versus placebo at various time points within the first 8 h in cats receiving robenacoxib. The most frequently reported adverse events were incision site infection/dehiscence, bleeding, vomiting, decreased appetite and lethargy. Frequencies of reported adverse clinical signs, hematology, serum chemistry and urinalysis variables, and body weight changes were similar between groups. There were no significant changes from baseline with robenacoxib in hepatic, hematological or renal clinical pathology variables.

          Conclusions

          Robenacoxib by s.c. injection was effective and well tolerated in the control of post-operative pain associated with orthopedic, ovariohysterectomy and castration surgery in cats.

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          Most cited references21

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          Nonsteroidal anti-inflammatory drugs in cats: a review.

          To review the evidence regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in cats.
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            Missing data handling in chronic pain trials.

            In chronic pain trials, proper handling of missing data due to dropout is an important issue because the dropout rate is high and the study conclusion may depend on the method chosen. The intent-to-treat (ITT) principle usually requires imputations for missing data to include the dropouts as well as completers in the statistical analysis. However, a statistical analysis with imputation might lead to a misinterpretation of clinical data. In chronic pain trials, treatment-related dropouts are clinical outcomes themselves. For example, an early dropout due to toxicity usually indicates a treatment failure, as does a dropout due to lack of efficacy. Problems with traditional methods such as last observation carried forward (LOCF) or baseline observation carried forward (BOCF) are identified especially in the chronic pain setting. Alternative methods, such as continuous responder analysis and two-part model analysis, treating dropouts as clinical events, are introduced with an example of osteoarthritis clinical trial data.
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              Postoperative analgesia in the cat after ovariohysterectomy by use of carprofen, ketoprofen, meloxicam or tolfenamic acid.

              The adequacy of postoperative analgesia was assessed in 40 cats following ovariohysterectomy. At extubation, cats were given one dose of carprofen, ketoprofen, meloxicam or tolfenamic acid. Postoperative analgesia was assessed using visual analogue scale (VAS) scoring for pain and sedation; measurement of mechanical nociceptive thresholds at the wound; recognition of the requirement for rescue intervention analgesia; and an overall clinical assessment score at 18 hours. VAS pain scores were low throughout the trial, with no significant differences found between the groups. Postoperative mechanical nociceptive thresholds decreased significantly from baseline in all four groups, with no significant differences between the groups. One cat in each of the tolfenamic acid, ketoprofen and meloxicam groups required rescue intervention analgesia. Nine out of 10 cats in all four groups were classified as having desirable overall clinical assessment scores. In summary, all four drugs provided good postoperative analgesia, although none was able to prevent postoperative wound tenderness.
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                Author and article information

                Contributors
                stephen.king@elanco.com
                Esr547@icloud.com
                jonathan.king@elanco.com
                Journal
                BMC Vet Res
                BMC Vet. Res
                BMC Veterinary Research
                BioMed Central (London )
                1746-6148
                29 September 2016
                29 September 2016
                2016
                : 12
                : 215
                Affiliations
                [1 ]Elanco Animal Health, Companion Animal Development, Greensboro, NC 27408 USA
                [2 ]Elanco Animal Health, Companion Animal Development, Basel, CH-4058 Switzerland
                Article
                827
                10.1186/s12917-016-0827-0
                5041542
                27686251
                a46c0ed7-a986-439e-82df-d5050dfeb276
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 April 2016
                : 1 September 2016
                Funding
                Funded by: Elanco Animal Health
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Veterinary medicine
                cat,injectable,post-operative,pain,nsaid,randomized,robenacoxib
                Veterinary medicine
                cat, injectable, post-operative, pain, nsaid, randomized, robenacoxib

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