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 Randomized Clinical Trial Evaluating Metabolism of Colostral and Plasma Derived Immunoglobulin G in Jersey Bull Calves

Background

Intravenous plasma administration has been recommended in healthy or sick calves with failure of passive immunity.

Hypothesis

IV administered plasma‐derived immunoglobulin G (IgG) undergoes increased catabolism as reflected by a rapid decrease in serum IgG concentration with an increase in fecal IgG concentrations within 48 h.

Animals

Thirty newborn Jersey calves. Fifteen were fed colostrum (CL group) and 15 were given bovine plasma IV (PL group).

Materials and Methods

Randomized clinical trial. Calves in the CL group were fed 3 L of colostrum once, by oroesophageal tubing. Calves in the PL group were given plasma IV at a dosage of 34 mL/kg. Serum and fecal samples were collected at 0 h, 6 h, 12 h, 48 h, 5 d, and 7 d. Serum and fecal IgG concentrations were determined by radial immunodiffusion.

Results

Calves in the CL group maintained serum IgG concentrations consistent with adequate transfer of immunity (≥1,000 mg/dL) throughout the study period. Calves in the PL group achieved median IgG concentrations of ≥1,000 mg/dL at 6 h but the concentrations were <1,000 mg/dL by 12 h. Calves in the PL group were 5 times more likely to experience mortality compared to the CL group (hazard ratio = 5.01). Fecal IgG concentrations were not different between the 2 groups during the first 48 h (P > .05).

Conclusions and Clinical Importance

Catabolism of plasma derived IgG occurs rapidly during the first 12 h after transfusion. Fecal excretion did not explain the fate of the plasma derived IgG.     

Efficacy and Toxicity of Doxorubicin/Cyclophosphamide Maintenance Therapy in Dogs with Multicentric Lymphosarcoma

Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P less than 0.04). Nineteen dogs were evaluable for toxicity. Dose-limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol.     

The Use of Hetastarch as Adjunct Therapy in 26 Dogs With Hypoalbuminemia: A Phase Two Clinical Trial

The purpose of this study was to evaluate the safety and efficacy of the synthetic colloid hetastarch in dogs with hypoalbuminemia. Individual doses of hetastarch ranged from 9 to 27 mL/kg, and multiple doses were used frequently. Total doses ranged from 9 to 59 mL/kg. Colloid oncotic pressure was measured in 13 dogs before and after treatment. Mean colloid oncotic pressure ± SD was 9.32 ± 2.35 mm Hg before treatment and 16.41 ±1.61 mm Hg in 8 healthy pet dogs used as controls. The difference in these values was significant ( P < .001). There was a significant increase in mean colloid oncotic pressure after the first dose of hetastarch, but there was no relationship between the dose of hetastarch and the magnitude of increase in colloid oncotic pressure. Peripheral edema or body cavity transudates resolved or decreased in 83% of the dogs despite concurrent use of crystalloid fluid therapy. There was also no relationship between the dose of hetastarch and resolution of edema. Worsening of the results from coagulograms occurred in 5 of 18 dogs, and included increased prothrombin time (n = 1), increased partial thromboplastin time (n = 5), and decreased platelet count (n = 3). Bleeding that occurred in 3 dogs could not be directly attributed to the hetastarch. There was no relationship between the dose of hetastarch and worsening of the values in the coagulograms.     

Amlodipine: A Randomized, Blinded Clinical Trial in 9 Cats with Systemic Hypertension

The efficacy of amlodipine (AML) was tested in hypertensive cats in a placebo-controlled, randomized, blinded clinical trial. Five cats were randomized to receive 0.625 mg AML once daily and 4 cats to receive placebo (PLA) once daily. The average systolic blood pressure (SBP) recorded by the Doppler method on day 0 was 212 ± 21 mm Hg in the AML group and 216 ± 32 mm Hg in the PLA group. On day 7, the cats receiving AML had a significantly lower average daily SBP (160 ± 30 mm Hg) but SBP in the PLA group was unchanged (207 ± 31 mm Hg). On day 7, all cats receiving PLA and one cat receiving AML were crossed over to the other group because of inadequate response. Blood pressure did not decrease adequately in 3 cats by day 14 (7 days of PLA and 7 days AML) and the treatment code was broken. Each of these cats was subsequently administered 1.25 mg AML daily. Cats requiring 1.25 mg AML once daily (6.1 kg ± 0.7 kg) weighed significantly more than cats that responded to 0.625 mg AML once daily (4.1 ± 0.7 kg). The average daily SBP recorded in the 6 cats that completed the study was significantly lower after 16 weeks of treatment (152 ± 14 mm Hg) compared to day 0 (221 ± 24 mm Hg). Three cats were euthanized before completion of the study. All 3 cats were responders to AML on day 7. SBPs measured 24 hours after AML administration were similar to the average daily SBP, suggesting that AML effectively controlled SBP for a 24-hour period. AML was shown to be an effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 ± 0.03 mg/kg sid.     

Intermittent and Continuous Enteral Nutrition in Critically Ill Dogs: A Prospective Randomized Trial

Background: Malnutrition is a common problem in critically ill dogs and is associated with increased morbidity and mortality in human medicine. Enteral nutrition (EN) delivery methods have been evaluated in humans to determine which is most effective in achieving caloric goals. Objectives: To compare continuous infusion and intermittent bolus feeding of EN in dogs admitted to a critical care unit. Animals: Fifty‐four dogs admitted to the critical care unit and requiring nutritional support with a nasoenteric feeding tube. Methods: Prospective randomized clinical trial. Dogs were randomized to receive either continuous infusion (Group C) or intermittent bolus feeding (Group I) of liquid EN. The percentage of prescribed nutrition delivered (PPND) was calculated every 24 hours. Frequencies of gastrointestinal (GI), mechanical, and technical complications were recorded and gastric residual volumes (GRVs) were measured. Results: PPND was significantly lower in Group C (98.4%) than Group I (100%). There was no significant difference in GI or mechanical complications, although Group C had a significantly higher rate of technical complications. GRVs did not differ significantly between Group C (3.1 mL/kg) and Group I (6.3 mL/kg) and were not correlated with the incidence of vomiting or regurgitation. Conclusions and Clinical Importance: There was a statistically significant difference in the PPND between continuously and intermittently fed dogs, but this difference is unlikely to be clinically relevant. Critically ill dogs can be successfully supported with either continuous infusion or intermittent bolus feeding of EN with few complications. Increased GRVs may not warrant termination of enteral feeding.