Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled,randomized, double-blinded,prospective clinical trial

Background

The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD) refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation. The aim of our trial was to assess the effect of tylosin on fecal consistency compared with a placebo treatment in dogs with suspected TRD and additionally to establish whether tylosin in dogs with recurrent diarrhea is as effective as empirical studies and anecdotal reports suggest.

Methods

Subjects comprised 71 client-owned dogs that, according to the owners, had previously been treated successfully with tylosin due to recurrent diarrhea of unknown etiology. At the initial examination, where there were no signs of diarrhea, the dogs were randomly assigned in a 2:1 ratio to a tylosin or placebo group. During a two-month follow-up the owners evaluated the fecal consistency according to previously published guidelines. When diarrhea recurred, either tylosin (25 mg/kg q 24 h, 7 days) or placebo treatment was initiated orally. Treatment outcome was evaluated as the mean of fecal consistency scores assigned during the last three days of the treatment period. To test for differences between the tylosin and placebo group in the proportion of responders, Pearson''s Chi-squared test and Fisher''s exact test were applied.

Results

Sixty-one dogs met the selection criteria and were followed for two months. During the follow-up 27 dogs developed diarrhea and either tylosin or placebo treatment was started. The proportion of dogs with normal fecal consistency at the end of treatment was 85% (17/20) in the tylosin group and 29% (2/7) in the placebo group (Pearson''s Chi-squared test p = 0.0049 and Fisher''s exact test two-sided, p = 0.0114).

Conclusions

Our findings indicate that tylosin is effective in treating recurrent diarrhea in dogs. The dose of 25 mg/kg once daily appears sufficient. No changes specific to TRD were detected in the examinations.     

The effects of capsaicin topical therapy in dogs with atopic dermatitis: a randomized,double-blinded,placebo-controlled,cross-over clinical trial

Abstract The efficacy of twice daily topical application of capsaicin (0.025%) for the management of pruritus in dogs with atopic dermatitis (AD) was evaluated in double-blinded, placebo-controlled study. Twelve dogs with AD were randomly assigned to either 0.025% capsaicin or vehicle lotion applied twice daily for 6 weeks. After a 4-week wash-out period, treatments were switched. Significant improvement was reported by owners ( P  = 0.0006), but not by investigators. Owners noted temporary worsening of pruritus after the first week of capsaicin therapy. Overall capsaicin was well tolerated. Substance P (SP) concentrations in the skin did not correlate with the severity of the pruritus and did not change significantly over time and between treatments. Lesional skin had less SP than nonlesional skin ( P  = 0.03). These observations suggest that topical capsaicin should be further evaluated as an adjunctive antipruritic agent in dogs with AD.     

Eprinomectin treatment of psoroptic mange in hunter/jumper and dressage horses: a prospective, randomized, double-blinded, placebo-controlled clinical trial

The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of topical eprinomectin for the treatment of psoroptic mange infestation in horses. 24 privately owned hunter/jumper and dressage horses were diagnosed with psoroptic mange infestation based on physical findings and skin scraping results were enrolled and randomly assigned to either topical eprinomectin pour-on solution (at a dose of 500mug/kg body weight weekly once for four applications) treatment group or a placebo group (purified water). Clinical evaluations and skin scrapings were done by the same veterinary investigator at the beginning, during and at the end of the treatment. Both owners and veterinary investigator were blinded to the allocation to the groups. The efficacy of eprinomectin was assessed both clinically and parasitologically by the presence or absence of viable mites. Horses were scraped for psoroptic mites on days 7, 14, 21, 28 and 40 for follow-up. Fisher's exact test was used to assess differences between the eprinomectin treatment and placebo in the number of horses without mites (cure rates) on each assessment date. It was found that significantly fewer eprinomectin treated horses had P. equi mites detected on skin scrapings (p<0.01) than the placebo group. In conclusion, eprinomectin was effective and safe therapy against natural infestations of P. equi in the horses included in this study.     

The clinical and histopathological effects of prednisone on acute radiation-induced dermatitis in dogs: a placebo-controlled, randomized, double-blind, prospective clinical trial

This study evaluated and compared the clinical and histopathological effects of prednisone on acute radiation-induced dermatitis (ARID) in dogs treated with 48 Gray of fractionated irradiation targeted to the skin surface. The study was designed as a double-blind, randomized, placebo-controlled prospective clinical trial. Twenty-two otherwise healthy companion dogs completed the clinical study. Three dogs were excluded from complete histopathological analysis because the owner declined one (one dog) or both (two dogs) biopsies. The study duration for each dog was 36 days from the start of radiation therapy (RT) to the first re-examination post RT. Dogs were treated with either oral prednisone at 0.5 mg kg(-1) or sugar pill, daily. All dogs received 48 Gray of fractionated, standardized RT, beginning 2 weeks after tumour excision. Acute Radiation Morbidity Scores, Cutaneous Toxicity Extent and Severity scores, digital images, and impression cytology were carried out on days 1, 8, 15, 22 and 36. Four-millimetre skin specimens from days 15 (RT-11) and 36 (2 weeks after the last RT dose) were scored by a pathologist and a dermatologist, blind to specimen identity. A one-way analysis of variance for longitudinal data was used to compare scores between groups. Spearman's rho correlation coefficient was used to measure strength of association between clinical and histopathology scores (HPS). There was no significant difference in CUTES, AMS or HPS scores between groups. There was a strong correlation between clinical and HPS scores. Prednisone did not decrease ARID severity clinically or histopathologically.     

Tepoxalin reduces pruritus and modified CADESI-01 scores in dogs with atopic dermatitis: a prospective, randomized, double-blinded, placebo-controlled, cross-over study

Thirty dogs with atopic dermatitis were given tepoxalin (Zubrin®, Intervet/Schering-Plough Animal Health, Boxmeer, the Netherlands) or placebo once daily for 4 weeks, followed by a wash-out period of 1 week before reversing the treatments. Pruritus was scored by the owners using the Edinburgh Pruritus Scale and one investigator employed a modification of the Canine Atopic Dermatitis Extent and Severity Index-01 (mCADESI-01) to score the physical lesions. After administration of tepoxalin there was a ≥ 50% reduction in pruritus and mCADESI-01 scores in 36% and 25% of the dogs, respectively, whereas following administration of the placebo there was a ≥ 50% reduction in pruritus and mCADESI-01 scores in only 25% and 16% of the dogs, respectively. Analysis of pooled data indicated that tepoxalin resulted in a significant reduction in pruritus ( P  = 0.012) and mCADESI-01 ( P  = 0.002) scores but there was no significant change after placebo. The median pruritus scores before and after tepoxalin were 2 (range 1–5) and 1 (range 0–5), respectively, and before and after placebo were 2 (range 0–4) and 2 (range 0–4), respectively. The median mCADESI scores before and after tepoxalin were 23 (range 0–68) and 16 (range 0–72), respectively, and before and after placebo were 18 (range 3–79) and 24 (range 0–65), respectively. At the dose used in this study (10.0–19.1 mg kg⁻¹), tepoxalin was well-tolerated and no adverse effects were noted.     

Evaluation of S-adenosyl l-methionine in a double-blinded, randomized, placebo-controlled, clinical trial for treatment of presumptive osteoarthritis in the dog

Objective: To evaluate the efficacy of S‐adenosyl l ‐methionine (SAMe) in the treatment of clinically inferred canine osteoarthritis (OA). Study Design: Six weeks, double‐blinded, placebo‐controlled, clinical trial. Animals: Dogs (n=33) with clinical signs, history, and orthopedic exams consistent with OA. Methods: Dogs were block randomized by body condition score (<6/9, or ≥6/9) into either the placebo or SAMe group. Outcome was assessed using pressure platform gait analysis, examination score, goniometry, and the Canine Brief Pain Inventory (CBPI) at the time of study entrance and at 3 and 6 weeks after entry. Groups were compared using parametric and nonparametric paired tests as appropriate, and numbers needed to treat (NNT) were calculated for the CBPI and peak vertical force (PVF). Results: Both groups (n=15 placebo, n=18 SAMe) had a reduction in mean PVF (P=.02) and vertical impulse (VI; P=.06) from the 1st to 3rd visit. There was no significant difference between the placebo group and SAMe group for PVF, VI, or either part of the CBPI (Severity or Impact). The NNT at 6 weeks for the Severity score was 3, Impact score was 25, and PVF was 45. Conclusions: These data do not support the use of SAMe as an effective stand alone treatment for reducing clinical signs of OA, as measured by PVF, VI, goniometry, CBPI (both Severity and Impact), and examination score within 6 weeks of treatment.     

Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial

Oral S-adenosylmethionine (SAMe) tosylate supplementation (Novifit tablets, Virbac) was evaluated as a dietary aid for the management of age-related mental impairment in dogs. Thirty-six dogs older than 8 years that had displayed signs of cognitive dysfunction for at least 1 month were selected for the study. The dogs were administered 18 mg/kg SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months. Concurrent behavioral treatment was forbidden. A 14-item standardized questionnaire evaluated behavior and locomotion difficulties. Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01). The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs.     

Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate injury in dogs: a randomized, placebo-controlled clinical trial

OBJECTIVE: To evaluate the efficacy of pentosan polysulfate (PPS) for improving the recovery period and mitigate the progression of osteoarthritis (OA) of the canine stifle after extracapsular stabilization of cranial cruciate ligament (CCL) injuries. STUDY DESIGN: Randomized, blinded, placebo-controlled clinical trial. ANIMALS: Dogs (n=40) with unilateral CCL instability. METHODS: Each dog had an extracapsular stabilization of the stifle with or without partial meniscectomy. Dogs were divided into 4 groups based on preoperative radiographic assessment and whether a partial meniscectomy was performed. Dogs were randomly assigned to either (3 mg/kg) PPS or placebo treatment in each group, and then injected subcutaneously weekly for 4 weeks. Lameness, radiographic changes, biological marker concentration in blood and urine, and ground reaction forces (GRFs) were collected preoperatively, and at 6, 12, 24, and 48 weeks. Data were analyzed within and between groups using repeated measures ANOVA; P<.05 was considered significant. RESULTS: No adverse reactions to PPS were reported. Thirty-nine dogs completed a minimum of 24-weeks follow-up and 33 dogs completed 48 weeks. All dogs clinically improved after surgery without differences in lameness score, vertical GRFs, or radiographic progression. Grouped and evaluated only by initial radiographic score, PPS-treated dogs improved significantly faster in braking GRFs than placebo-treated dogs. In dogs with partial meniscectomies, urine deoxypyridinoline, and serum carboxy-propeptide of type II collagen were significantly increased at 6 weeks in placebo-treated dogs compared with PPS-treated dogs. CONCLUSIONS: PPS administered after stabilization of the cruciate deficient stifle may prove to be a useful adjunctive treatment option, although further studies are necessary to substantiate this claim.     

Investigation on the clinical efficacy and tolerability of a 0.4% topical stannous fluoride preparation (MedEquine Gel) for the treatment of bacterial skin infections in horses: a prospective, randomized, double-blinded, placebo-controlled clinical trial

The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy and tolerability of a novel gel containing 0.4% stannous fluoride (MedEquine) for the treatment of cutaneous bacterial infections in horses. Twenty privately owned horses diagnosed with bacterial skin infections based on physical findings and cytology results were enrolled and randomly assigned to either a placebo or an active ingredient treatment group. The product was applied on affected areas daily for 4 weeks. Cytology and clinical evaluations were done by the same investigator at the beginning and at the end of the treatment. Owners scored pruritus weekly. Both owners and investigators were blinded to the allocation to the groups. At the end of the study, stannous fluoride gel treatment significantly decreased the investigator's clinical scores and owners' pruritus scores while no significant changes were detected in the vehicle treatment group. At the end of the trial, none of the horses in the stannous fluoride group required additional therapy while four of ten horses in the vehicle group required systemic therapy to resolve the infection. No adverse effects were detected in any of the groups. The gel formulation made compliance easier for owners compared to the traditional bathing regimen and allowed spot treatment, which was particularly helpful in animals with localized infections. These favourable aspects of the treatment were highlighted by the owners of the horses enrolled in the study. In conclusion, 0.4% stannous fluoride gel (MedEquine) was an effective and safe therapy for the topical management of bacterial skin infections in the horses included in the study.     

Recombinant bactericidal/permeability-increasing protein (rBPI21) for treatment of parvovirus enteritis: a randomized, double-blinded, placebo-controlled trial

We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent, the recombinant amino terminal fragment of bactericidal permeability-increasing protein (rBPI21), to decrease plasma endotoxin concentration and severity of clinical signs of canine parvovirus and to improve survival. This randomized, double-blinded, placebo-controlled clinical trial included 40 client-owned dogs and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb) with fecal antigen-confirmed parvovirus and clinical signs of vomiting and diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6 hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of infusion. Owners chose continued medical care with either the Veterinary Hospital of the University of Pennsylvania Internal Medicine Service or a local veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were reevaluated at >30 days (recovered group), at which time plasma samples for measurement of endotoxin concentration were obtained. Plasma endotoxin concentrations were significantly higher in dogs with parvovirus than in normal or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a significant effect on outcome, duration of hospitalization, or plasma endotoxin concentrations. Treatment in a tertiary care hospital, however, significantly improved survival but resulted in a significantly increased duration of hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21 is not associated with improved survival.     

The effect of thyroid replacement in dogs with suboptimal thyroid function on owner-directed aggression: A randomized,double-blind,placebo-controlled clinical trial

The efficacy of thyroid hormone replacement therapy (THRT) as treatment for owner-directed aggression in client-owned dogs with borderline low thyroid hormone levels was evaluated by means of a 6-week-long, parallel design, double-blind placebo-controlled study. The designation of “borderline hypothyroid” was made if the dog's free normal thyroxine (T4) value was frankly low or in the bottom 20th percentile of the normal range and either total T4, total triiodothyronine (T3), or free T3 was frankly low or in the bottom 30th percentile of the normal range. The presence of thyroid autoantibodies also qualified a dog for enrollment. Owners recorded the number of aggressive episodes directed toward family members on a daily basis for 8 weeks (2-week baseline phase and 6-week study phase). Twenty-nine dogs completed the study; 14 in a treatment group and 15 in a placebo group. The median number of aggressive episodes per day decreased significantly from baseline in both treated and placebo group dogs in weeks 1-2, 3-4, 5-6, and week 6 (treatment, χ² = 24.8, P < 0.001; placebo, χ² = 20.2, P < 0.001), however the median frequency of aggression was significantly lower in the treatment group (1.21 episodes/day) than in the placebo group (1.71 episodes/day) during week 6 of the study (χ² = 4.047, P = 0.044). Three thyroxine-treated dogs had borderline-low thyroid levels on the final day of the study (day 42). When aggression frequency was compared between the treatment and placebo groups after the removal of 3 thyroxine-treated dogs, the treatment group did not have a significantly lower aggression frequency than the placebo group during week 6 (Kruskal–Wallis statistic: χ² = 3.035, n = 26, P = 0.08). The authors discuss the role of thyroid hormones in the regulation of aggression and other cognitive issues and provide rationale for using THRT in dogs exhibiting owner-directed aggression that also have low normal or baseline thyroid hormone levels.     

Stratification, blinding and placebo effect in a randomized, double blind placebo-controlled clinical trial of gold bead implantation in dogs with hip dysplasia

The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore detected. CONCLUSION AND CLINICAL RELEVANCE: The age of the dogs influenced the outcome of the CHD treatment, and is recommended as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary in similar clinical studies.     

A prospective,randomized, blinded,placebo-controlled multisite clinical study of bedinvetmab,a canine monoclonal antibody targeting nerve growth factor,in dogs with osteoarthritis

ObjectiveBedinvetmab is a canine monoclonal antibody targeting nerve growth factor. This study evaluated the efficacy and safety of bedinvetmab for alleviation of pain associated with osteoarthritis in dogs.Study designDouble-blind, randomized, multicentre, placebo-controlled study.AnimalsClient-owned dogs (n = 287) with osteoarthritis.MethodsDogs were randomized (1:1) to subcutaneous injection with placebo (saline, n = 146) or bedinvetmab (0.5–1.0 mg kg^–1, n = 141) administered monthly. After 3 months, 89 bedinvetmab-treated dogs that responded positively based on owner and veterinarian assessments were administered up to six additional doses of bedinvetmab in a single-armed open-label continuation phase. The primary efficacy end point was treatment success based on the owner-assessed canine brief pain inventory (CBPI) on day 28. Treatment success was defined as ≥ 1 reduction in pain severity score (0–10) and ≥ 2 in pain interference score (0–10).ResultsPercentage treatment success was significantly greater in the bedinvetmab group than in the placebo group from day 7 through all assessed time points (p ≤ 0.0025). On day 28, 43.5% of dogs achieved treatment success with bedinvetmab compared with placebo (16.9%) (p = 0.0017). Treatment success continued through days 56 (50.8%) and 84 (48.2%) in the bedinvetmab group and was < 25% in the placebo group at all time points. Sustained efficacy was demonstrated in the continuation phase. Adverse health events occurred at similar frequencies in both groups. They were considered typical for a population of dogs with osteoarthritis and not related to study treatment. Treatment with bedinvetmab demonstrated a significant effect on all three components of CBPI—pain interference, pain severity, quality of life.Conclusions and clinical relevanceThis study demonstrated the effectiveness and safety of bedinvetmab administered monthly for up to 9 months at 0.5–1.0 mg kg^–1 for alleviation of pain associated with canine osteoarthritis.     

Failure of terfenadine as an antipruritic agent in atopic dogs: results of a double-blinded, placebo-controlled study.

Terfenadine (5 mg/kg body weight, q12h) and placebo (0.5 grain/dog q12h) were both administered orally as individual agents to 18 dogs with atopy in a double-blinded study. No dog improved. Hyperactivity, polyphagia, lethargy, anorexia, increased pruritus, or ocular discharge were seen in three dogs treated with terfenadine. Under the conditions of the study, terfenadine was not a useful antipruritic agent for the atopic dog.     

Failure of cyproheptadine hydrochloride as an antipruritic agent in allergic dogs: results of a double-blinded, placebo-controlled study.

Cyproheptadine hydrochloride was administered orally at 0.1 to 0.2 mg/kg/day to 16 dogs with allergic pruritus. No dog improved. Polyphagia was observed in 4 dogs (25%).