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

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The effect of a dietary supplement (Succeed™) on gastric ulcer severity

Nicola Kerbyson BVMS Cert AVP (EM) MRCVS Derek Knottenbelt OBE BVM&S DipECEIM MRCVS Tim Parkin BSc, BVSc, PhD, DipECVPH, FHEA, MRCVS

School of Veterinary Medicine College of Medical, Veterinary and Life Sciences University of Glasgow n.kerbyson.1@research.gla.ac.uk

Aim

• To assess the effects of a dietary supplement

(Succeed™) on the development and treatment of squamous gastric ulceration in racing TBs

• Supplement contains polar lipids, beta glucan, yeast,

glutamine and threonine

• Marketed as a digestive supplement to assist in the

healing of ulcers

• Non-inferiority trial

Materials and Methods

• 56 horses recruited to trial
• Inclusion criteria:

– In active race or pre-race training – Have ≥ grade 1 squamous ulceration (Equine Gastric Ulcer Council grading system – Not have received any treatment or preventive treatment for gastric ulceration in preceding 28days Equal mix of flat and NH from 2 yards

The Equine Gastric Ulcer Council, 1999. Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS). Equine Vet.

• Educ. 11, 262–272.

Materials and Methods

• Each horse randomly assigned to 1 of

2 groups:

– Group A- 4mg/kg omeprazole q24hrs – Group B- 27g Succeed digestive conditioning programme/horse/day PO

• Gastroscopy repeated at day 30,60

and 90

• Gastroscopy videos scored by 3

blinded assessors (DipECEIM)

Median grade

Reviewer 3 Reviewer 2 Reviewer 1

If >1 reviewer stated a video was non-diagnostic- removed from analysis Reviewers asked to grade from 0-4

• r non-diagnostic

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

Inter-operator agreement good Weighted kappa= 0.72-0.8 >90% agreement

Retention

56 56 48 43 10 20 30 40 50 60 30 60 90 Number of Horses Number of Days

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Reasons for horses leaving trial

Tendon injury Sold/moved yard Upper airway surgery Cardiac disease

Results Day 0

A single horse for which the initial analysis and diplomate analysis did not agree

Day 30

Chi2- P values for differences between treatments ≤1 grade ≤2grades 0.02 0.001

Day 60

Chi2- P values for differences between treatments ≤1 grade ≤2grades 0.04 0.24

Day 90

Chi2- P values for differences between treatments ≤1 grade ≤2grades 0.71 0.72

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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

• Chi2 tests (Fishers exact) demonstrated no significant

difference between the two groups in terms of improvement in squamous gastric ulcer grade at day 90

Group <2 grades improvement ≥2 grades improvement P value Succeed 20 4 0.72 Omeprazole 15 4 Group <1 grade improvement ≥ 1grade improvement P value Succeed 14 10 0.71 Omeprazole 10 9

Summary of Chi2 analysis

• A significant effect of omeprazole was observed at

day 30 in terms of improvement by 1 or 2 grades and at day 60 in terms of improvement by 1 grade.

• There was no difference between treatments at day

90 (neither treatment resulted in significant improvement)

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McNemars

≥2 (Squamous) Day 0-30 Day 0-60 Day 0-90 Succeed 0.69 0.75 1.0 Omeprazole 0.001 0.001 0.06 ≥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

Results

There was no statistically significant improvement in severity of squamous ulceration with treatment at the label dosages for either omeprazole or Succeed™ following 90 days of treatment.

Withdrawal periods

• 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
• r 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

Total and longest consecutive withdrawals Analysis of effect of withdrawal

• However with so few observations of a positive
• utcome in the omeprazole group this may be

underpowered

• Hence…
• Mann-Whitney non parametric tests performed which

showed no significant difference in the total withdrawal or consecutive withdrawal times for either

• utcome measurement

Acknowledgements

• Freedom Health for funding the trial
• Dr Tim Parkin
• Professor Derek Knottenbelt
• Sycamore Lodge and Troytown Greyabbey

Veterinary Surgeons

• The Irish Equine Centre

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Analysis of effect of withdrawal

• Looked at the effect of both the total withdrawal

period and the longest number of consecutive withdrawal days on

– Likelihood of having a grade of 2 or less at day 90 – Likelihood of improvement by 2 or more grades

• Logistic regression with 4 combinations of outcome

and explanatory variables- none significant

• However with so few observations of a positive
• utcome in the omeprazole group this may be

underpowered

Analysis of effect of withdrawal

• No difference in effect of omeprazole in horses due

to withdrawal

– But- likely to be at least partially due to lack of horses with a positive outcome – Difficult to establish the true effect of withdrawal without having a control group with no withdrawal but there were none of these in the population studied