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Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage<jats:italic>D. immitis<\/jats:italic>larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24\u00a0\u00b5g\/kg moxidectin, 2\u00a0mg\/kg sarolaner and 5\u00a0mg\/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24\u00a0\u00b5g\/kg) or sarolaner-alone (2\u00a0mg\/kg). Efficacy was evaluated ~\u20095\u00a0months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs \u2265\u20098 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24\u201348\u00a0\u00b5g\/kg moxidectin, 2\u20134\u00a0mg\/kg sarolaner and 5\u201310\u00a0mg\/kg pyrantel (<jats:italic>n<\/jats:italic>\u2009=\u2009272) or Heartgard\u00ae Plus (ivermectin\/pyrantel) at the label recommended dose rate (<jats:italic>n<\/jats:italic>\u2009=\u2009138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20\u201344 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard\u00ae Plus tested positive. The Heartgard\u00ae Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard\u00ae Plus tested positive.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13071-019-3702-6","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T23:04:57Z","timestamp":1568156697000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Laboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs"],"prefix":"10.1186","volume":"12","author":[{"given":"Kristina","family":"Kryda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Six","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly F.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Holzmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Chapin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Mahabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Inskeep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jady","family":"Rugg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair","family":"Cundiff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleah","family":"Pullins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ulrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"McCall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom L.","family":"McTier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Maeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,11]]},"reference":[{"key":"3702_CR1","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1128\/CMR.00012-12","volume":"25","author":"F Sim\u00f3n","year":"2012","unstructured":"Sim\u00f3n F, Siles-Lucas M, Morch\u00f3n R, Gonz\u00e1lez-Miguel J, Mellado I, Carret\u00f3n E, et al. 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The clinical field study protocol was reviewed and approved by the Zoetis Ethical Review Board and owner consent to participate was obtained prior to patient enrolment.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"These studies were funded by Zoetis. KK, RHS, KFW, SJH, SC, SPM, MM, TI, JR, BC, AP, TLM and SJM were employees of Zoetis. MU and JWM were contracted study investigators.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"445"}}