Table 2 Summary of the key results

Ivermectin s.c. vs. placebo

298 mixed-breed dogs, housed in 12 pens containing 10 to 60 dogs; 70% severe form; 25% moderate form; 5% mild form.

Diagnostic method: skin scrapes and/or clinical.

Ivermectin, 200 μg/kg:

Group A (n=20), Group D (n=256): D0; D14

Group B (n=12), Group C (n=10): D14.

Vehicle/Sterile solution 0.9% NaCl:

Group B (n=12), Group C (n=10): D0.

% efficacy D14: Group A=95%; Group B=42%; Group C=30%.

Group A, B, C: parasitological cure D14 following the 2^nd ivermectin treatment.

Group D: D42 clinically similar to Group A.

Major improvement in skin lesions and

pruritus in all groups.

Animals enrolled only based on clinically compatible signs.

Out of the total number of enrolled animals (n=298), only a medium number of animals (n=42) were monitored systematically.

D42 data refers to 5 dogs in group A and B and 3 dogs in group C.

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Oral milbemycin oxime

Phase one: 27 owned dogs, 3 mongrels and 24 pure breeds.

Diagnostic method: skin scrapes (n=22) and/or clinical (n=5).

Milbemycin oxime, 2 mg/kg: D0, D7, D14.

All in-contact dogs were treated.

50% to 75% reduction in pruritus after the 3rd dose.

Two dogs relapsed after 2.5 months.

D28: clinical cure.

Uncontrolled study

Animals enrolled only based on clinical compatible signs.

Medium or small number of animals.

No control test for parasites during and/or at the end of the study.

Lack of quantitative outcome.

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Phase two: 14 dogs, Beagle, housed in the same facility in groups of 4.

Diagnostic method: skin scrapes (performed randomly) and/or clinical.

D0, D14, milbemycin oxime, 2 mg/kg.

All dogs were clinically normal at the end of the study and 10 months after.

One dog died due to events unrelated to the therapy.

Topical ivermectin 0.5%

120 dogs, 118 mixed-breed, housed into 35 pens containing from 2 to 5 dogs/pen; severe in 15 dogs; moderate in 70 dogs; mild in 35 dogs.

Diagnostic method: skin scrapes (performed randomly) and/or clinical and/or fecal flotations (performed randomly)

0.5% pour-on ivermectin, 500 μg/kg: D1 and D15

Ivermectin, s.c., 300 μg/kg on D1 and D15 to all animals entering or departing the shelter

90 of the 120 dogs present on D1 were still at the shelter on D150.

D15: Major improvement in skin lesions and pruritus in all dogs.

D30: clinical remission observed in all but 2 dogs.

D150: clinical remission in all dogs (n=90)

Uncontrolled study

Animals enrolled only based on clinically compatible signs.

Control tests were conducted randomly and irregularly.

Lack of quantitative outcome.

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Topical spot-on selamectin 12% vs. placebo

30 dogs, 17 mixed-breed and 13 purebreds from kennels (USA), 12 purebred dogs from hunting kennels (Italy).

Dogs were housed in purpose-designed buildings in a single site in each country.

Diagnostic method: skin scrapes.

Selamectin, min. 6 mg/kg or vehicle: D0 and D30

Dogs were randomly allocated to vehicle (15 dogs in USA; 6 in Italy) or selamectin (15 dogs in USA; 6 in Italy) group.

3 dogs were withdrawn from the study (2 from vehicle group Italy and 1 from selamectin group USA).

Parasitological cure in selamectin group: D29/30, Italy and D44, USA.

The mean count mite in the selamectin treatment was significantly lower than that in the vehicle treatment in both studies on all evaluation days.

Major improvement in skin lesions and pruritus in both selamectin groups.

Medium or small number of animals.

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Topical spot-on 12% selamectin vs. N-(mercaptomethyl) phthalimide S-(0,0-dimethyl phosphorodithioate), dip solution, in USA; vs. phosmet, sponge-on, in UK; vs. amitraz, body-wash solution, in Italy.

207 dogs, purebred and mix-breed, housed both indoors and outdoors, in USA and Europe (UK and Italy)

Diagnostic method: skin scrapes.

Selamectin, min. 6 mg/kg^: D0 and D30; N-(mercaptomethyl) phthalimide S-(0,0-dimethyl phosphorodithioate), 7.8 mL l-1, 1 to 8 doses, D0, D14, D21, D28, D35, D42, D49, D56; phosmet 0.09%, 1 to 4 doses, every 14 days; amitraz 0.025%, 2 to 4 doses, D0, D7, D30, D37.

Animal allocation:

USA: Selamectin n=54; positive control (PC) =19. Europe: Selamectin n=68; positive control (PC) =37.

29 dogs did not complete the study.

The efficacy of selamectin was >95% by day 30, and 100% by day 60.

Improvement in skin lesions and pruritus in all treatment groups.

The reason for the withdrawal from the study was not given for all the animals.

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Oral or s.c. moxidectin.

41 owned dogs of various breeds

Diagnostic method: skin scrapes (n=3) or serological (n=17) or therapeutical (n=21).

0.2–0.25 mg/kg moxidectin, administrated once / week until clinical signs were gone (3-6 weeks):

orally (n=4) or subcutaneously (n=31), the first dose was given subcutaneously and the following orally (n=6).

All in-contact dogs were treated.

4 dogs were withdrawn from the study (3 because of side effects).

7 dogs treated s.c. showed side effects.

Clinical cure in all remaining 37 dogs.

Uncontrolled study.

Lack of quantitative outcome.

Small or medium number of animals.

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Topical spot on: imidacloprid 10% + moxidectin 2.5% vs. 12% selamectin.

58 owned dogs

Diagnostic method: skin scrapes and clinical criteria.

Imidacloprid 10% + moxidectin 2.5% (n=27) and 12% selamectin (n=26): D0 and D28.

Five dogs were withdrawn due to events unrelated to treatment.

Parasitological cure rate on D56 was 100% in both study groups and

>96% of the dogs in both groups were clinically cured or improved.

One dog treated with selamectin showed side effects.

Medium number of animals.

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Topical spot on: imidacloprid 10% + moxidectin 2.5% vs. 12% selamectin.

30 owned mixed-breed dogs, housed individually

Diagnostic method: skin scrapes.

Imidacloprid 10% + moxidectin 2.5% (n=15) and 12% selamectin (n=15): D0 and D28.

One dog treated with Imidacloprid 10% + moxidectin 2.5% was withdrawn due to events unrelated to treatment.

Parasitological cure starting from D22 in both groups.

Marked improvement in skin lesions and pruritus in both treatment groups by D36.

Three dogs in the selamectin group had concurrent demodicosis.

Medium number of animals.

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Ivermectin s.c. vs. ivermectin s.c. + vitamin E + selenium.

31 dogs (9 healthy and 22 dogs infested with sarcoptic mites)

Diagnostic method: skin scrapes.

Collection of blood samples to estimate oxidative stress indices, hematology, and biochemical panels: D0 and D28.

1% ivermectin s.c. 0.2 mg/kg (n=11, Group 2), 1% ivermectin s.c. 0.2 mg/kg + (tocopherol 50 mg + Se 1.5 mg/mL) 0.5 mL/20 kg i.m. (n=11, Group 3): weekly, three times.

Antihistamines: 5-7 days for all infested dogs.

Parasitological cure rate D28: Group 2 = 82%; Group 3 = 100%.

Marked improvement in skin lesions

in both treatment groups by D28, with maximum recovery in Group 3.

D28: significantly alleviated malonyldialdehyde in Group 2 and 3; CAT and SOD were significantly elevated in both groups; GSH was significantly elevated in group 3.

Small number of animals.

No data provided on the animals’ housing.

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Oral sarolaner vs. placebo.

Study 1: 44 owned mixed breed dogs, individually housed.

Diagnostic method: skin scrapes.

Sarolaner, 2 mg/kg (n=22), Placebo (n=22): D0 and D30.

I.m. or s.c. dexamethasone (0.4 mg/kg, 3 adm. /week for two weeks) in 10 dogs from each group, before or after the first treatment.

2 dogs in the sarolaner group and 4 in the placebo group were withdrawn due to events unrelated to treatment.

The efficacy in the sarolaner group compared to the placebo group or relative to the pre-treatment mean was >99% in all post treatment evaluations.

Parasitological cure for sarolaner group vs. placebo group on D30: 100% vs 65%.

Immunosuppression therapy during the study.

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Oral sarolaner vs spot-on imidacloprid + moxidectin.

Study 2: 79 primary and 45 supplementary (in-contact) owned dogs.

Diagnostic method: skin scrapes.

Sarolaner, 2mg/kg (n=53), imidacloprid/moxidectin group (n=26): D0 and D30.

All in-contact (supplementary) dogs were treated with the same molecule and frequency as the primary dog: Sarolaner, 2 mg/kg (n=26), imidacloprid/moxidectin group (n=19): D0 and D30.

Parasitological cure in the sarolaner group vs. imidacloprid + moxidectin group, on D60: 100% vs. 96%.

Marked improvement in skin lesions and

pruritus in both treatment groups

One dog in the imidacloprid/moxidectin group was under-dosed at D30.

7 dogs in the sarolaner group received concomitant antimicrobial and/or anti-inflammatory treatment, due to various medical events.

Oral afoxolaner.

20 owned mixed-breed dogs.

Diagnostic method: skin scrapes.

Afoxolaner, min. 2.5 mg/kg (n=11): D0 and D28.

Control group (n=11): not treated.

Parasitological cure, by day 28: afoxolaner group, efficacy 100%, Control group 10%.

Significant improvement in skin lesions and pruritus in the afoxolaner group by day 56.

Small number of animals.

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Oral fluralaner.

17 owned dogs.

Diagnostic method: skin scrapes.

Fluralaner, min. 25 mg/kg: D0.

Parasitological cure by day 14.

Significant reduction in lesions by day 14.

Significant reduction in pruritus by days 14 to 21.

Uncontrolled study

Medium number of animals.

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Oral and topical spot-on fluralaner vs. placebo.

29 owned mixed-breed dogs.

Diagnostic method: skin scrapes.

Oral fluralaner min. 25 mg/kg (n=9), topical fluralaner 25 mg/kg (n=11), topical saline solution (n=9): D0.

All the dogs from the same household were enrolled in the same treatment group.

3 dogs in the topical fluralaner group did not complete the study due to events unrelated to treatment.

Parasitological cure by D28: 100% in treated groups, 33.3% in placebo group.

Improvement in skin lesions and pruritus in both treated groups by D28.

Small number of animals.

No post-treatment clinical evaluation of the control group.

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Oral afoxolaner and oral afoxolaner + milbemycin oxime.

80 owned, mixed-breed and purebred dogs.

Diagnostic method: skin scrapes.

Oral afoxolaner (n=38) and oral afoxolaner + milbemycin oxime (n=27), 2 administrations: D0 and D26-D30.

14 dogs were excluded due to non-compliance and 1 was erroneously enrolled.

Parasitological cure by two months after the first treatment: 99.7% afoxolaner group, 100% afoxolaner + milbemycin oxime group.

Significant improvement in pruritus and skin lesions two months after the first treatment

Uncontrolled study

No data provided regarding the group assignment of excluded animals.

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Oral and topical spot-on fluralaner and oral sarolaner.

Owned, mixed-breed and purebred dogs: 135 primary and 19 supplementary (in-contact) dogs.

Diagnostic method: skin scrapes.

Oral and topical spot-on fluralaner, min. 25 mg/kg: D0, and oral sarolaner, min. 2 mg/kg: D0 and D28.

All the dogs from the same household were enrolled in the same treatment group.

9 dogs were excluded due to non-compliance (3 dogs in the topical fluralaner group, 1 dog in the oral fluralaner group, and 5 dogs in the oral sarolaner group).

Parasitological cure, efficacy 100% by D56 in all groups.

Substantial improvement in pruritus and skin lesions in all groups by D56.

Clinical and parasitological cure in all groups by D84.

2 dogs, 1 in the sarolaner group, and 1 in the fluralaner spot-on group, received oral antibiotics.

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Oral afoxolaner and oral afoxolaner + milbemycin oxime.

142 owned dogs.

Diagnostic method: skin scrapes.

Oral afoxolaner + milbemycin oxime (n=96) and oral afoxolaner (n=46): D0.

Clinical cure in both groups by D56.

Absence of pruritus in the afoxolaner + milbemycin oxime group by D28 and in the afoxolaner group by D56.

No data provided on parasitological cure.

No data provided on group allocation.

Not mentioned if it is a blind study.

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