Ongoing Clinical Study to Evaluate the Benefit of Intravenous Fosphenytoin for the Emergency Treatment of Seizures in Dogs

By Michael Podell MSc, DVM, Diplomate ACVIM (Neurology)

A prospective clinical study is currently underway at CVESC under the direction of Dr. Michael Podell to evaluate the benefit of a novel drug therapy for status epilepticus/cluster seizures in canine epilepsy. 

We are conducting a controlled clinical trial to determine if intravenous (IV) Fosphenytoin (FOS), in conjunction with our standard of care for seizures in dogs, improves the clinical outcome. The study is being conducted by veterinarians from the Veterinary Medical Center of the College of Veterinary Medicine of the University of Minnesota, and the University of Pennsylvania, College of Veterinary Medicine, and Chicago Veterinary Emergency and Specialty Center. Half of the dogs in this study will randomly be assigned to get a one-time dose of 25 milligrams per kilogram (mg/kg) of body weight Phenytoin Equivalents (PE) of IV FOS over 5-15 minutes (based on body weight) if they have further seizures while in the hospital. This dosage is the standard dose of FOS given to human patients in the emergency room. The other half of the dogs will randomly be assigned to get an equal volume of sterile saline at this point as the control group. In addition to the one time IV injection of FOS or saline, each patient will also be treated according to the veterinary standard of care thereafter if the seizures continue and/or the initial seizure in the hospital lasts more than 10 minutes.

The goal of this study is to develop an improved treatment protocol for canine seizure emergencies and to develop more information for future studies in dogs that may later lead to new anticonvulsant therapies in people and dogs.

BACKGROUND 

IV FOS or IV Phenytoin is the most common emergency drug treatment in people if benzodiazepines, such as diazepam or lorazepam, have not stopped seizure activity. FOS is converted in the blood to Phenytoin, and FOS has fewer side effects when given IV than straight IV Phenytoin due to removal of propylene glycol. An initial study in normal dogs given an IV dose of 25mg/kg (PE) of FOS over 5 to 10 minutes did not produce any significant adverse effects during or after the injection for up to 24 hours in terms of cardiac, biochemical or neurological changes.

WHO QUALIFIES? 

A dog with epileptic seizures qualifies for enrollment if: 

• Two or more seizures occurred without returning to normal behavior or activity in-between seizures within 12 hours prior to admission.

• Any single seizure lasting more than 5 minutes within the prior 12 hours and has already had at least one treatment with a first line benzodiazepine drug (often diazepam).

• Any underlying cause of seizures except for metabolic related disease.

 

HOW DO YOU ENROLL A PATIENT? 

A dog is enrolled into the study if: 

• Meets the inclusion criteria.

• Owner signs a consent form and completes a general health questionnaire.

• Patient is admitted to the hospital for a minimum of 6 hours if no seizures are observed.

• Patient is admitted to the hospital for a minimum of 12 hours if another seizure occurs and study drug is administered.

 

COMPENSATION 

• The client receives up to a $500 credit on the invoice if the patient has no further seizures in the next 5 hours after admission.

• The client receives up to a $1500 credit, if the patient has any further seizures while in the hospital for the next 5 hours and then gets the IV study injection, followed by our standard treatments if the seizures continue to occur and/or last more than 10 minutes.

• All additional charges will be the responsibility of the client. The attending doctor will give the client an estimate for the total costs of all charges and keep them updated on a daily basis.

 

RISKS AND INCONVENIENCES 

The risks and inconveniences that may occur are as follows:

• Except for the 5-15 minute injection of FOS or saline control, the patient will receive care following our standardized treatments for the emergency treatment of seizures. Dogs with frequent or prolonged seizures can potentially have life threatening increases in brain pressure or secondary organ damage. The standard treatments alone often cause sedation or sleepiness, and even when done carefully have the potential to cause life threatening effects on breathing and on the heart.

• Even though we have tested IV FOS in normal dogs and shown no significant adverse effects, this is the first study to evaluate this drug in epileptic dogs that are also being treated with other antiepileptic drugs. Due to limited experience with FOS in dogs, previously unreported side effects could potentially arise. We will watch carefully for these or any other adverse effects and treat them whenever possible.

• We will get 3 extra blood samples to measure FOS blood levels.

 

Please address any further questions to:

Dr. Michael Podell, Diplomate ACVIM (Neurology)
Chicago Veterinary Emergency and Specialty Center
mpodell@cvesc.net 

Dr. Ned Patterson, DACVIM (Small Animal Internal Medicine)
Department of Small Animal Clinical Sciences
University of Minnesota College of Veterinary Medicine
patte037@umn.edu 

This study has been approved by the University of Minnesota Institutional Animal Care and Use Committee (IACUC) and the University of Pennsylvania IACUC. If you have any question or concerns contact:

Moira Keane, University of Minnesota, Director, Research Subjects’ Protection Programs 612-626-5654.

 

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