07/04/2015 Aim The effect of a dietary supplement (Succeed ) on - PDF document

07/04/2015 Aim The effect of a dietary supplement (Succeed ™) on gastric • To assess the effects of a dietary supplement ulcer severity (Succeed™) on the development and treatment of squamous gastric ulceration in racing TBs Nicola Kerbyson BVMS Cert AVP (EM) MRCVS Derek Knottenbelt OBE BVM&S DipECEIM MRCVS • Supplement contains polar lipids, beta glucan, yeast, Tim Parkin BSc, BVSc, PhD, DipECVPH, FHEA, MRCVS glutamine and threonine School of Veterinary Medicine College of Medical, Veterinary and Life Sciences • Marketed as a digestive supplement to assist in the University of Glasgow n.kerbyson.1@research.gla.ac.uk healing of ulcers • Non-inferiority trial Materials and Methods Materials and Methods • 56 horses recruited to trial • Each horse randomly assigned to 1 of 2 groups: • Inclusion criteria: – Group A- 4mg/kg omeprazole q24hrs – In active race or pre-race training – Group B- 27g Succeed digestive – Have ≥ grade 1 squamous ulceration (Equine Gastric Ulcer conditioning programme/horse/day PO Council grading system – Not have received any treatment or preventive treatment for gastric ulceration in preceding 28days • Gastroscopy repeated at day 30,60 and 90 Equal mix of flat and NH from 2 yards • Gastroscopy videos scored by 3 blinded assessors (DipECEIM) The Equine Gastric Ulcer Council, 1999. Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS). Equine Vet. Educ. 11, 262–272. Grading of videos Retention Reviewer 1 60 Reviewer 2 56 56 Reviewers asked 50 Number of Horses to grade from 0-4 48 Inter-operator Reviewer or non-diagnostic 40 43 3 agreement good The Equine Gastric Ulcer Weighted 30 Council, 1999. kappa= 0.72-0.8 Recommendations for the diagnosis and treatment of 20 >90% agreement equine gastric ulcer syndrome (EGUS). Equine Vet. Educ 11 262–272. 10 Median grade 0 0 30 60 90 Number of Days If >1 reviewer stated a video was non-diagnostic- removed from analysis 1

07/04/2015 Reasons for horses leaving trial Results Cardiac disease Upper airway surgery Tendon injury Sold/moved yard Day 0 Day 30 Chi 2- P values for differences between treatments ≤ 1 grade ≤ 2grades 0.02 0.001 A single horse for which the initial analysis and diplomate analysis did not agree Day 60 Day 90 Chi 2- P values for Chi 2- P values for differences differences between between treatments treatments ≤ 1 grade ≤ 2grades ≤ 1 grade ≤ 2grades 0.04 0.24 0.71 0.72 2

07/04/2015 Day 30 Day 60 Conclusions- Day 90 Results • Treatment effect assessed at 2 levels: – Proportion of horses improving by 1 or 2 grades – Proportion of horses with clinically significant ulceration at day 90 (assessed at both Grade ≥ 2 and Grade ≥ 3) Statistical analysis- Day 0-90 Summary of Chi 2 analysis • Chi 2 tests (Fishers exact) demonstrated no significant • A significant effect of omeprazole was observed at difference between the two groups in terms of day 30 in terms of improvement by 1 or 2 grades and improvement in squamous gastric ulcer grade at day at day 60 in terms of improvement by 1 grade. 90 Group <2 grades ≥ 2 grades P value • There was no difference between treatments at day improvement improvement 90 (neither treatment resulted in significant Succeed 20 4 0.72 improvement) Omeprazole 15 4 Group <1 grade ≥ 1grade P value improvement improvement Succeed 14 10 0.71 Omeprazole 10 9 3

07/04/2015 McNemars Results ≥ 2 (Squamous) Day 0-30 Day 0-60 Day 0-90 There was no statistically significant improvement in Succeed 0.69 0.75 1.0 severity of squamous ulceration with treatment at the label dosages for either omeprazole or Succeed™ Omeprazole 0.001 0.001 0.06 following 90 days of treatment. ≥ 3 (Squamous) Day 0-30 Day 0-60 Day 0-90 Succeed 0.55 0.51 1.0 Omeprazole 0.29 0.11 1.0 P values represent the likelihood that each treatment will result in a gastric ulcer score of ≥ 2 or ≥ 3 at the time point Withdrawal periods Total and longest consecutive withdrawals • Standard withdrawal periods applied to omeprazole throughout the trial • 11/20 horses in omeprazole group had withdrawal periods applied • No difference in likelihood of improving by 2 grades or more or having a grade of ≤ 2 at day 90 (Chi2) • The effect of the withdrawal time has been analysed by logistic regression- no difference Analysis of effect of withdrawal Acknowledgements • However with so few observations of a positive • Freedom Health for funding the trial outcome in the omeprazole group this may be • Dr Tim Parkin underpowered • Professor Derek Knottenbelt • Sycamore Lodge and Troytown Greyabbey • Hence … Veterinary Surgeons • The Irish Equine Centre • Mann-Whitney non parametric tests performed which showed no significant difference in the total withdrawal or consecutive withdrawal times for either outcome measurement 4

07/04/2015 Analysis of effect of withdrawal Analysis of effect of withdrawal • Looked at the effect of both the total withdrawal • No difference in effect of omeprazole in horses due period and the longest number of consecutive to withdrawal withdrawal days on – But- likely to be at least partially due to lack of horses with a positive outcome – Likelihood of having a grade of 2 or less at day 90 – Difficult to establish the true effect of withdrawal without – Likelihood of improvement by 2 or more grades having a control group with no withdrawal but there were • Logistic regression with 4 combinations of outcome none of these in the population studied and explanatory variables- none significant • However with so few observations of a positive outcome in the omeprazole group this may be underpowered 5