Study compares Simparica Trio and NexGard Plus against resistant heartworm isolate

A peer-reviewed laboratory study funded by Zoetis found that Simparica Trio-treated dogs had significantly lower average heartworm counts than NexGard Plus-treated dogs following experimental challenge with the macrocyclic lactone-resistant Dirofilaria immitis ZoeLA isolate.
  • Simparica Trio-treated dogs had significantly lower average heartworm counts than NexGard Plus-treated dogs (P = 0.0316).
  • Simparica Trio demonstrated 99.5% efficacy against the ZoeLA isolate compared with 98.1% for NexGard Plus.
  • Adult heartworms were found in 2 of 8 Simparica Trio-treated dogs and 6 of 8 NexGard Plus-treated dogs.
  • At day 237, 1 of 8 Simparica Trio-treated dogs and 4 of 8 NexGard Plus-treated dogs tested positive for heartworm antigen.
  • No Simparica Trio-treated dogs had detectable microfilariae at the end of the study, compared with one dog treated with NexGard Plus.
  • No treatment-related adverse events were recorded in any dog.

A peer-reviewed laboratory study published in Parasites & Vectors compared Simparica Trio and NexGard Plus against a macrocyclic lactone-resistant heartworm isolate in dogs.

The controlled study evaluated Zoetis’ Simparica Trio (sarolaner, moxidectin and pyrantel chewable tablets) and NexGard Plus (afoxolaner, moxidectin and pyrantel chewable tablets) against the Dirofilaria immitis ZoeLA isolate.

Twenty-four dogs were experimentally challenged with the resistant isolate and then received one of the two products or a negative control monthly for six months at the standard labeled dosage.

At the end of the study, one adult heartworm was found in each of 2 of 8 dogs treated with Simparica Trio. One adult heartworm was found in each of 6 of 8 dogs treated with NexGard Plus.

Study reports difference in average worm counts

Simparica Trio-treated dogs had an average adult worm count of 0.2 compared with 0.7 among NexGard Plus-treated dogs.

The difference in average heartworm counts was statistically significant (P = 0.0316).

Efficacy compared with the untreated control was 99.5% for Simparica Trio and 98.1% for NexGard Plus.

At day 237, 1 of 8 Simparica Trio-treated dogs tested positive for heartworm antigen compared with 4 of 8 dogs treated with NexGard Plus.

No dogs treated with Simparica Trio had detectable microfilariae in their blood at the end of the study. Microfilariae were detected in 1 of 8 dogs in the NexGard Plus group.

No treatment-related adverse events were recorded in any dog.

Study examines moxidectin dosage

Both products contain moxidectin, which kills heartworm larvae before they develop into adult worms.

Simparica Trio delivers a minimum moxidectin dosage of 24 µg/kg per dose, while NexGard Plus provides a minimum of 12 µg/kg per dose.

In the ZoeLA study, adult heartworms were found in 75% of NexGard Plus-treated dogs compared with 25% of Simparica Trio-treated dogs.

Jessica Rodriguez, therapeutic area lead for companion animal parasiticides, Veterinary Medicine Research and Development at Zoetis, said the findings demonstrate the importance of moxidectin dosage when veterinarians are considering prevention in areas where macrocyclic lactone-resistant heartworm is circulating.

Lindsay Starkey, veterinary parasitologist at Oklahoma State University’s College of Veterinary Medicine and a board member of the American Heartworm Society, said differences in active ingredient, dosage and formulation can affect efficacy and compliance, emphasizing on-label dosing and consistent year-round administration.

Second head-to-head study of the products

According to the release, this is the second controlled head-to-head study comparing Simparica Trio and NexGard Plus against a macrocyclic lactone-resistant heartworm isolate.

An earlier study evaluated the JYD-34 isolate. In both studies, fewer Simparica Trio-treated dogs became infected with adult heartworms than NexGard Plus-treated dogs.

The ZoeLA study was published as Rodriguez J, Jones S, Mahabir S, DiCosty U, Mansour A, Fricks C, McCall JW, Geurden T. “Comparative efficacy of six monthly doses of Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets) versus NexGard® Plus (afoxolaner, moxidectin, and pyrantel chewable tablets) against a macrocyclic lactone-resistant Dirofilaria immitis isolate in dogs.” Parasites & Vectors (2026) 19:259.

The study was funded by Zoetis.

Simparica Trio safety information

Simparica Trio should be used with caution in dogs with a history of seizures. The product contains sarolaner, a member of the isoxazoline class, which has been associated with neurologic adverse reactions including tremors, ataxia and seizures in dogs with or without a history of neurologic disorders.

The safe use of Simparica Trio has not been evaluated in breeding, pregnant or lactating dogs. The most frequently reported adverse reactions in clinical trials were vomiting and diarrhea.

NexGard and NexGard Plus are registered trademarks of Boehringer Ingelheim Animal Health USA Inc. Simparica Trio is a registered trademark of Zoetis Services LLC.

Information sourced from the company’s press release.

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