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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 or 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

All gastroscopies diagnostic

Fourth gastroscopy completed

Third gastroscopy completed

Second gastroscopy completed

Treatment group assigned

Squamous ulceration of grade 1 or above

Underwent initial gastroscopy 66

52 (79%)

29 Succeed

26 (90%)

26 (90%)

23 (80%)

22 (76%)

23 Omeprazole

23 (100%)

23 (100%)

19 (83%)

19 (83%)

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Reasons for horses leaving trial

Tendon injury

Sold/moved yard

Upper airway surgery

Cardiac disease

Starting squamous ulcer grade

9

8

2

4

8

7

2

0

1

2

3

4

Squa

mou

s ul

cer g

rade

Omeprazole Succeed

Results Non-inferiority analysis

•  Many clinical studies compare the effectiveness of two treatments rather than a treatment vs placebo

•  Historically when two treatments are compared to assess if they are significantly different from one another

•  This difference may be significant but not clinically relevant

•  Non-inferiority analysis includes an assessment of the clinical significance of the difference

Non-inferiority analysis 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

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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)

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 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

Total and longest consecutive withdrawals Analysis of effect of withdrawal

•  However with so few observations of a positive outcome 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 outcome measurement

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Acknowledgements

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

Veterinary Surgeons •  The Irish Equine Centre

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 outcome 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