This multi-center, positive-controlled field study was conducted in alignment with the Good Clinical Practice, VICH Guideline 9 [15], Guideline on Statistical Principles for Veterinary Clinical Trials (EMA/CVMP/EWP/81976/2010) [16] and with the Guideline for the Demonstration of Efficacy of Ectoparasiticides (7AE17a, Sep 1994) [17] at 9 veterinary clinics across Albania, France, Italy and Portugal. At each site, the study activities were distributed between an unmasked Dispenser, who was responsible for treatment assignments and administrations, but took no part in clinical assessments, and an Examiner who was masked and made all treatment-related observations, including skin scrapings and skin lesion evaluation.
Enrolment of dogs
Dogs with clinical signs of sarcoptic mange (pruritus, papules, crusts, erythema) and at least one live S. scabiei mite (larva, nymph, adult) found in at least one deep skin scraping qualified for the study [13]. Any dogs sharing a household with an enrolled dog were treated with the same product, regardless of the presence or absence of a positive skin scraping or clinical signs. Every household dog with at least one live S. scabiei mite before treatment was evaluated for efficacy, but mite-negative dogs were not monitored for infestation status and were included in the safety evaluation only (additional dogs).
Dogs remained at home during the study. Grooming and bathing were not permitted within 3 days after the initial treatment (Day 0) but were allowed for all groups on all subsequent study days. Dogs were not included if they received any medication, such as macrocyclic lactones, that might interfere with the efficacy assessment. During the study, dog treatment with any products with insecticidal/acaricidal or insect growth regulator activity was not permitted. No premises sanitation with products having acaricidal or insecticidal activity was allowed within 2 months before study start or during the study.
Treatments
Each dog was allocated randomly to one of three treatment groups, in a ratio of 2:2:1, to receive oral fluralaner (Bravecto® chewable tablets, MSD Animal Health, Schwabenheim, Germany), topical fluralaner (Bravecto® Spot-on, MSD Animal Health), or oral sarolaner (Simparica®, Zoetis, Louvain-la-Neuve, Belgium), respectively. All treatments were administered in accordance with label directions, and all dogs within a study household were treated on the same day. Fluralaner was administered once at the approved dose rate of 25–56 mg/kg on Day 0, while sarolaner was administered at 2–4 mg/kg on Days 0 and 28 (4 weeks later) according to its approved label in Europe against S. scabiei. Dogs showing clinical signs of bacterial pyoderma received oral antibiotic treatment where recommended by the Examiner (two dogs, one in the sarolaner group, and one in the fluralaner spot-on group, required this treatment). Owners were instructed to carefully observe their dog(s) and advise the clinic of any unfavorable events between each scheduled visit.
Assessments of sarcoptic mange
At the enrolment visit (Day 0) and at subsequent visits on Days 28, 56 and 84, deep skin scrapings were taken from at least five different body areas that showed the most severe lesions (crusts, alopecia, erythema, papules) suggesting the likely presence of local mite infestation. Each scraping, taken over an area of approximately 2.5 cm2, was made in the direction of hair growth with a blade or spatula coated with mineral oil, to an approximately constant depth so that capillary oozing was evident. When obtaining a scraping was difficult (area difficult to access), hairs were plucked from an affected area and placed in mineral oil. The scraping was examined for the presence of live mites under a stereomicroscope and the assessment of the scraping results was based on mite counts and clinical signs. If no mites were detected in five scrapings in a dog showing clinical signs, then additional scrapings were made until live mites were found, or until the maximum of 10 scrapings was reached. If no mites were detected in the first five scrapings in dogs without clinical signs, then no additional scrapings were made. The total number of mites counted in all scrapings was recorded. If needed, dogs could be sedated to allow effective skin scraping. Subsequent to Day 0, the same affected area was scraped on each visit if possible. However, if the area of the previous scraping appeared normal and other lesions were present, then the new lesions were scraped. When there were no observed lesions, the previous lesional areas were scraped.
At each scheduled visit, and before skin scraping (and treatment), the presence and severity of skin lesions, i.e. erythema, pustules/papules, crusts/scales, alopecia and any other dermatological signs, were recorded. The Examiner also scored each dog’s level of pruritus using a scale of 0 (no pruritus) to 10 (extreme pruritus).
Assessing results
Primary efficacy was determined from the percentage of dogs free of live mites at the last evaluation (Day 84, week 12) for each study group [17]. Secondary efficacy parameters were determined from the percentage of dogs free of live mites on Days 28 and 56, and the regression of pruritus, alopecia and other skin lesions was evaluated.