SPORTS MEDICINE, LAMENESS, AND REHABILITATION
injection in the neck with the gauge of needle of the clinician’s preference. The subsequent injections were given on the opposite side of the neck from the previ- ous injection site and at least 3 inches from the previ- ous injection when on the same side. This protocol was used to enable the assessment of injection sites. The treatment dispenser had access to previous visits to determine location. Any concomitant treatment during the study period was documented in the study records.
Physical Examinations
The investigator performed a physical examination and then a lameness score based on the AAEP Lameness Scale11 pretreatment on SD 0, SD 7 (6 2days), SD 14 (6 2days), SD21 (6 2days), SD28 (6 2days), and any unplanned visits. Injection site observations were per- formed by the investigator pretreatment on SD 0, SD 7 (6 2days), SD 14 (6 2days), and SD 21 (6 2days) to confirm the site was normal prior to injection (full neck assessed). Approximately 3hours postinjection (6 15minutes), the investigator observed the injection sites. Following treatment, the owner was asked to re- cord an injection site observation in the days between visits. On SD 28, the investigator made a full assess- ment of the neck to confirmthat all injection site obser- vations had resolved. Injection site observations were obtained at unplanned visits if deemed appropriate by the investigator. In addition to injection site observa- tions, owners were asked to maintain a daily diary re- cord on the general, appetite, and drinking habits and if the horse was considered normal/abnormal for the pe- riod of time between each visit. Owners were instructed to report any potential adverse events (AEs) to the in- vestigator. A follow-up phone call to the owner took place on SD38 (6 2days).
Clinicopathology
Blood and serum samples were collected for clinical pathology (complete blood count and serumchemistry with fibrinogen) on SD 0 (pretreatment), SD 14 (pre- treatment), SD 28, and any unplanned visits if indicated in response to an AE. Blood and serum samples were collected for prothrombin time (PT) and activated partial thromboplastin time (aPTT) analy- ses pretreatment and then 3hours post-treatment (6 15minutes) on SD0, SD14 (6 2days), and SD 21 (6 2days). All clinicopathologic analyses were per- formed at a single reference laboratory.d
Outcome Assessment
At enrollment, the investigator identified a single limb with lameness due to OA with radiographic evi- dence to support the diagnosis. This limbwas then fol- lowed in each subsequent lameness evaluations and used in the assessment of treatment effect. The end- point for efficacy was the improvement in lameness score at SD 28. SD 28 lameness scores were compared to SD 0 lameness scores. Animals with an improve- ment of at least 1 category in the SD 28 lameness score as compared to the SD 0 lameness score were
292 2022 / Vol. 68 / AAEP PROCEEDINGS
considered a treatment “success”;otherwise,the ani- mal would be classified as a “failure.” Should an animal have been withdrawn from the study for per- ceived inefficacy or failuretoimprove, or at any time for treatment-related reasons, they would have been classified as a failure. The success rate of the IVP treated group was then compared to the negative con- trol group to determine overall treatment effect. Any horses removed from the study for treatment-related reasons were considered treatment failures. Horses that did not complete all study visits due to treat- ment-related reasons are included in the effectiveness analysis as treatment failures. In addition, horses that completed all or any of the interim visits but did not complete the follow-up (Day 3862) phone call visits were included in the effectiveness analysis and deemed as a success or failure based on the last evaluation.
Adverse Events
For this study, an AE was defined as any unfavorable and unintended observation in a horse that occurred any time following administration of the IVP or CP, whether or not it was considered product related. Any AE that occurred during the study was reported to the investigator, who recorded the AE and any associ- ated concomitantmedication administered.
Data Analysis
The study was a negatively controlled, randomized, blinded field efficacy study. The investigator doing the physical examinations and lameness examinations and the owner/agent were blinded. The treatment ad- ministrator could not be blinded because of differences in color and packaging of the control and treatment materials. Treatment administration data and mate- rials were securely maintained by the treatment dministrator. Each animal was randomized in presen- tation order using randomization generated by the SAS statistical package also used for analysis.e Each study site utilized a separate randomization. Animals were blocked in groups of 4 in a 2:2 IVP to CP ratio. Masking was achieved by separation of function and access to treatment records. The individual horse was evaluated as the experimental unit. Descriptive statistics (number of observations, mean, standard deviation, minimum, and maximum (or number of observations, median, and frequency counts for bino- mial data) were generated for all variables at all vis- its. All hypotheses were tested at a two-sided 0.05 level of significance. Effectiveness was determined by the results obtained on Day 28. Animals havingmajor protocol deviations were not included in the effective- ness evaluation. The lameness scores from Day 28 were compared to the lameness scores at Day 0, and an animal was classified as a success if there was an improvement of at least one category in the Day 28 lameness scores; otherwise, the animal was classified as a failure. Animals withdrawn from the study for perceived inefficacy or failure to improve, or at any time for treatment-related reasons, were classified as
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