Heartworm Treatment Trial Compares Two and Three Melarsomine Doses

What happened

• A randomized clinical trial of 168 dogs compared a compressed two-dose melarsomine heartworm treatment with the three-dose protocol. It was published online in the Journal of the American Veterinary Medical Association on September 2, 2026, and dvm360 reported on it in late October ^1,2.
• The dogs were treated at a rescue campus in South Carolina, and PetSmart Charities funded the work ¹.

What the researchers did

Of 170 dogs enrolled, 168 were analyzed: 85 in the two-dose group and 83 in the three-dose group ¹. Both groups also received moxidectin, doxycycline and prednisone. Only dogs aged at least 12 months with class 1 or class 2 heartworm disease were included, and dogs with more severe disease were not enrolled ¹.

What they found

• Safety: all 168 dogs survived, and none needed intensive management or hospitalization ¹.
• Side effects: stomach and intestinal signs after melarsomine were less common with two doses (31.8%) than with three (48.2%) ¹.
• Efficacy: 95.3% of dogs in the two-dose group and 98.8% in the three-dose group tested antigen-negative at the final test. The difference was not statistically significant, but the researchers’ formal test of whether two doses were “non-inferior” was inconclusive ¹.

What this does and doesn’t mean

The American Heartworm Society has recommended the three-dose protocol for all dogs since 2005 ¹. This trial was aimed at shelter and rescue settings, where the three-dose approach can be hard to deliver, and it does not show that two doses are as good. Safety in dogs with more severe disease is unknown ¹.

Do not change a heartworm treatment plan on your own. If your dog has heartworm, your vet will choose the protocol. Prevention is far simpler than treatment, and our dog health guide explains year-round prevention and annual testing.

We read this trial through dvm360’s summary, not the full paper. The authors’ claims, such as it being the largest randomized heartworm trial, are theirs.