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Category: Dogs

Role of Drug-Specific T Cells in Idiosyncratic Sulfonamide Toxicity in Dogs (Study Closed)
July 21, 2011 (published)
Lauren Trepanier
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Study Start Date: 7/15/2011
Study End Date: 8/18/2012

Potentiated sulfonamide antibiotics, such as trimethoprim-sulfamethoxazole (TMP-SMX), Tribrissen, and Primor, can be used to treat urinary tract infections, otitis, pyometra, prostatitis, pneumonia, and atypical mycobacterial infections in dogs, as well as MRSA. However, dogs treated with sulfonamides can develop idiosyncratic drug toxicity reactions (also called sulfonamide hypersensitivity) that can include fever, skin eruptions, thrombocytopenia, hepatopathy, neutropenia, keratoconjunctivitis sicca, hemolytic anemia, arthropathy, or uveitis. Because these reactions are difficult to predict, and can even be fatal, they substantially limit the utility of an entire class of antimicrobials. A better understanding of the pathogenesis of sulfonamide hypersensitivity is therefore needed. We hypothesize that dogs with a history of hypersensitivity to potentiated sulfonamide antimicrobials will have circulating T cells that recognize the parent sulfonamide drug (sulfamethoxazole, sulfadiazine, or sulfadimethoxine), its oxidative metabolites, and/or trimethoprim or ormetoprim. This knowledge may lead to better predictive and preventative measures and allow safer use of these antimicrobials in dogs.

Study Design:
Prospective, Case-controlled

Sample Size:
This is an exploratory study. Our goal is 37 hypersensitive and 37 tolerant dogs over a one-year period. This will provide 85% power (at P < 0.05) to detect, as significantly different, a result of 50% of hypersensitive dogs with drug-specific T cells, compared to 19% of tolerant dogs.

Inclusion Criteria:

  • Dogs that have taken a standard therapeutic course of Primor, Tribrissen, or human generic TMP-SMX for at least 7 days, with adequate follow-up to determine whether they either had no adverse events, or developed clinical signs of fever, skin eruptions, thrombocytopenia, hepatopathy, neutropenia, keratoconjunctivitis sicca, hemolytic anemia, arthropathy, or uveitis, within 5 to 21 days of starting the drug.
  • Reactions must have been observed during therapy or within 1 week of stopping the sulfonamide, without other clinical explanation.
  • Blood should be drawn within one year of the adverse reaction or the most recent course of potentiated sulfonamides.

Exclusion Criteria:

  • Apparent adverse reactions to other sulfonamides that are not either Primor, Tribrissen, or human generic TMP-SMX. Topical administration only (e.g., silver sulfadiazine).
  • Administration of glucocorticoids or other immunosuppressive drugs within one month of blood draw.

Study Controls:
Dogs clinically normal after a 7 day or longer course standard of Primor, Tribrissen, or human generic TMP-SMX, without administration of glucocorticoids or other immunosuppressive drugs within one month of blood draw.

Study Endpoints:

  • Primary: Prevalence of drug-specific T cells in dogs with sulfonamide HS, compared to prevalence in dogs tolerant of a therapeutic course of a potentiated sulfonamide antibiotic
  • Secondary: Determine whether drug specific T cells target the parent sulfonamide, a sulfonamide metabolite, or trimethoprim/ormetoprim.

Samples:
One 10 ml blood sample in heparin, at room temperature, the same day as drawn. Please notify our lab by email before sending so that we can prepare reagents and send a brief sample questionnaire for inclusion, as well as a FedEx stamp.

Files for Download:
Consent Form
Sample Submission Form

Costs/Reimbursements:
Shipping costs will be covered by investigators

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Full Disclosure information:

  • The study is funded by a grant from NIH and intramural funds.
  • The investigator does not have a conflict of interest.
  • The study will be published if results are negative.
  • The study will be reported on VIN.
  • The authors will acknowledge VIN if the study is published.


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