A prospective, randomized, placebo-controlled, double-blinded clinical trial comparing the incidence and severity of gastrointestinal adverse events in dogs with cancer treated with piroxicam alone or in combination with omeprazole or famotidine
Shaevitz, M.H. et al. (2021) A prospective, randomized, placebo-controlled, double-blinded clinical trial comparing the incidence and severity of gastrointestinal adverse events in dogs with cancer treated with piroxicam alone or in combination with omeprazole or famotidine. Journal of the American Veterinary Medical Association, 259 (4), pp. 385-391.
The aim of this randomised placebo-controlled, double-blinded trial, which was carried at a Veterinary Teaching Hospital in the United States and funded by the Veterinary Cancer Society’s Resident Research Award, was to assess the impact of prophylactic administration of omeprazole or famotidine on the incidence and severity of gastrointestinal (GI) adverse events (AEs) in dogs with cancer treated with piroxicam.
Dogs with a cytologic or histologic diagnosis of cancer, that were being treated with piroxicam and that had no history of GI disease or NSAID-induced GI AEs, were recruited between July 2018 and August 2019. The target sample size for the study was 72 dogs (24 per group).
All dogs received 0.3 mg of piroxicam/kg (0.14 mg/lb), per os (PO), every 24 hours. The three treatments to which the dogs were randomly allocated were 1 mg of famotidine/kg (0.45 mg/lb) PO every 12 hours (famotidine group), 1 mg of omeprazole/kg PO every 12 hours (omeprazole group), or placebo (lactose) PO every 12 hours (placebo group). Dogs were clinically assessed at four-week intervals, owners completed surveys that included questions on appetite, eating and defecation habits, vomiting, and energy level, over the previous four weeks at the time of the assessment appointment. Owners were also encouraged to report any possible GI AEs between appointments. AEs were scored according to the Veterinary Comparative Oncology Group’s Common Terminology Criteria for Adverse Events. Both clinicians and owners were blinded to the randomisation scheme.
Thirty-nine dogs were enrolled in the study and randomised to a treatment group, 13 dogs in each. Recruitment to the trial was halted at day 56, due to the frequency of GI AEs observed in dogs in two of the treatment groups and an interim analysis was undertaken. Five dogs were excluded from the analysis, leaving 10 dogs in the famotidine group, 13 in the omepra¬zole group, and 11 in the placebo.
There was a significant difference in the percentage of dogs that had experienced GI AEs by day 56, in both the omeprazole group (84.6%) and famotidine group (80.0%) when compared to the placebo group (36.4%). The severity of GI AEs was higher in the omeprazole group compared to placebo with significantly more dogs having AEs that were graded as ≥ 2. There was no significant difference in the severity of AE between the famotidine and omeprazole groups and be¬tween the famotidine and placebo groups.
Whilst several dogs had increased serum liver enzyme activities at the time of enrolment, there was no association between increased liver enzyme activities on day 0 and the frequency or severity of GI AEs.
Limitations of the study include the small sample size and the fact that liver function was not directly assessed.
This study provides some evidence of the potential risks of using gastroprotectants in dogs being treated with piroxicam for cancer. Whilst the findings are not directly generalisable to other NSAIDs or other conditions, they do highlight the importance of ensuring the use of gastroprotectants is as evidence-based as possible. Additional research on the use of gastroprotectants with NSAIDS in other clinical situations is recommended.
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