[Ergoferon liquid dosage form--efficacious and safe treatment for childhood acute respiratory infections. Interim outcomes of a multi-center, randomized, double-blind, placebo-controlled clinical trial].

The pediatric dosage form of Egroferon--a drug indicated for the treatment of influenza and acute respiratory infections (ARIs)--is developed taking in account the broad range of pathogens (most of which are viruses), and age-dependent features of immune system reactions (absence of specific immunity and immunological memory, relative "immaturity" of immune reactions, reduced interferon production by immunocompetent cells, etc.). Ergoferon interferes with the non-specific mechanisms of antiviral defence that ensure eliciting of an immune response, regardless of the virus type (the interferon system and CD4+cells), and influences virus-induced histamine release and histamine-mediated inflammatory reactions. Used over four years in clinical practice, the drug has shown a high efficacy and safety profile for the treatment of influenza and ARIs in adult patients. The purpose of the multi-center, randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and safety of a new ergoferon liquid dosage form in the treatment of ARIs in children. The publication contains the results of the fist study stage completed as per the study plan and data from the interim analysis. METHODS. The screening involved a total of 162 subjects, aged 3 to 17 years (average, 8.2 ± 3.9 years), that had presented to 13 research centers based in Russia with common signs and symptoms of ARI (body temperature ≥ 38.0 degrees C, as measured with a digital infrared temporal artery thermometer; symptom severity score ≥ 4) during seasonal morbidity. Ergoferon was administered in 82 subjects receiving the therapeutic regimen of the drug for 5 days; 80 children received placebo. The subjects were monitored for 6 days. Treatment efficacy was assessed on the basis of morning, evening and total daily ARI symptom scores, including scoring estimates of fever, general symptoms and symptoms affecting the nose, throat and chest. Along with this, calculations were performed to obtain the Total Index (TI) of ARI; illness severity was evaluated using a mathematical "area under the curve" model. RESULTS. Starting from Day 2, the percentage of convalescents was observed to increase--from 6% (morning) and 14% (evening) to 20% and 29% on Day 3, respectively, and 58% and 61% on Day 4. The results suggested a substantially higher efficacy of Ergoferon as compared to placebo treatment (the Cochran-Mantel-Haenszel χ2 test: χ2 = 21.7; p < 0.0001). Ergoferon had a marked effect on fever and other signs of intoxication. In Ergoferon group, the percentage of non-fever subjects, with the endpoint defined at ≤ 37.2 degrees C, was 43% on Day 2, as estimated in the morning and the evening (vs 25% and 19% in the placebo group, respectively; χ2 = 10.6; p = 0.012), and 83% in the morning and 84% in the evening on Day 3 (vs 60% and 54% in the placebo group, respectively; χ2 = 16.7; p = 0.001). The Generalized Linear Model (GENMOD) procedure confirmed the significance of differences between the Ergoferon and placebo groups according to the following parameters: 1) Ergoferon was significantly more effective in reducing body temperature (to lower values) than the placebo; 2) Ergoferon had an earlier effect on fever (main marker of viremia), as compared to placebo; 3) The significant Ergoferon's superiority over placebo was also evident by the morning and evening measurements throughout the five-day therapy. The TI was observed to significantly decrease starting from Day 2 of Ergoferon administration: from 13.0 ± 4.5 to 7.9 ± 4.8 on Day 2 and 4.5 ± 2.9 on Day 3 (based on the patient's diary data); from 14.3 ± 4.2 to 4.9 ± 3.0 on Day 3 (based on the doctor's assessment). The severity of ARI-related intoxication signs was reduced most significantly, in particular as indicated by the results of doctor's objective examination on Day 3 (GENMOD: factor "Treatment"--χ2 = 147.8; p < 0.0001; factor "Day of administration"--X>=6.1; p = 0.013; Tukey-Kramer post hoc analysis: z = -3.09; p = 0.024). The average fever duration in ergoferon-treated subjects was 1.9 ± 0.8 days (p < 0.0001). The overall duration of ARI was much shorter in Ergoferon group than in the group of placebo (p = 0.021). The "area under the curve" measure of TI in Ergoferon group was significantly lower as compared to Placebo group, both according to the patient's diary records (21.9 ± 10.9 TI x Days vs 28.0 ± 13.0 TI x Days; p < 0.002) and the doctor's examination (12.4 ± 4.7 vs 14.2 ± 5.2 TI x Days; p = 0.023). Ergoferon treatment was associated with a lower frequency of using antipyretics (χ2 = 4.1; p = 0.043), particularly on the first day of illness. The monitoring of adverse events as well as the haematology, biochemistry and urinalysis findings were indicative of Ergoferon's safety. No signs of drug incompatibility were observed as a result of ergoferon administration in combination with antipyretics, decongestants, expectorants, inhaled corticosteroids, cromoglicic acid derivatives, leukotriene receptor antagonists, short-acting beta2 agonists and topical anti-septics. There were also no cases of bacterial complications, worsening of illness severity, or acute exacerbations of coexisting allergy or chronic ENT pathology. The children demonstrated good drug tolerance and 100% treatment compliance. CONCLUSIONS. Ergoferon liquid dosage form is an efficacious and safe treatment for ARIs in children. The study results demonstrated the drug's efficacy against the major syndromes associated and caused by viremia--fever and general intoxication. The early onset of the drug's effect was shown to result in a shorter time to convalescence and reduced ARI severity, particularly during the initial days of illness.

[Rengalin, a novel drug for treatment of cough in children. Intermediate data on multicentre, comparative randomized clinical trial].

UNLABELLED: Rengalin liquid formulation on the basis of antibodies to bradikinin histamine and morphine was specially designed for the treatment of cough in children. The three-component combination in therapeutically active against both dry and wet cough due to effect on diverse pathogenetic aspects of the cough reflex. The aim of the multicenter, comparative, randomized clinical trial was to estimate the efficacy and safety of rengalin in the treatment of cough in patients with acute respiratory infection (ARI) of the upper respiratory tract. METHODS: One hundred forty six patients at the age of 3 to 17 years (the average age of 8.2 ± 3.6 years) from 14 medical centres of Russia were observed. The patients suffered from dry/nonproductive, frequent, sore cough preventing from day-time activity and/or night sleep (≥ 4 by the Cough Severity Scale). The cough duration ranged from 12 hours to 3 days. For 3 days the patients of group 1 (n = 71) and group 2 (n = 75) were treated with rengalin and sinekod (butamirate) respectively. For the following 4 days the patients (in case of viscid expectoration were treated with ambroxole in the age doses. The results of the Per Protokol Analysis (n = 67 rengalin group and n = 73 sinekod group) with an account of the Non-Infectiority Design are presented. RESULTS: In 3 days the number of the group 1 patients with significant improvement/recovery by the day and night estimates amounted to 90% and 88% respectively (vs. 81% and 88% in the group 2 patients, no night opisodes of cough after 3-days rengalin use being recorded in 52% of the patients vs. 34% in the sinekod group patients (p = 0.0003). On the 7th day of the treatment with rengalin the number of the children with significant improvement of or recovery from day-time cought amounted to 99%and that of the patients with significant improvement of or recovery from night-time cough amounted to 93%, in 90% of them no night-time cough being recorded (p = 0.0008). As for the patients of the reference group, the respective values were 93% and 90%, no night-time cough being recorded in 81% of the patients. The time required for development of productive/moist cough during the 3-day treatment course in the patients of both the group was the same (2.9 ± 0.3 days in the patients of group 1 and 2.9 ± 0.4 days in the group 2 patients. Moreover, in 34% of the rengalin dry cough became residual (as rare episode of tussiculation with scantly exudation). After 3-day course of the rengalin therapy, 66% of the patients was treated with ambroxole (versus 95% in sinecod group (p < 0.0001) based on comparative analysis and χ2 = 17.7, p > 0.0001 by the results of the frequency analysis). The total duration of cough in the patients of groups 1 and 2 was 6.5 ± 0.8 and 6.7 ± 0.7 days respectively (the comparability truth, p = 0.0001). The severity of the day-time cough by the area under the curve estimates for 7 days of the treatment in the rengalin group patients was equel to 14.3 ± 5.6 numbers--days and that of the patients of the sinekod? group was equal to 15.9?6.1 numbers - days. The severity of the night-time cough was equal to 4.2 ± 2.7 number--days respectively. In 2 patients (3%) treated with sinekod signs of ARI generalization was observed after the 3-day treatment (p > 0.0001). The research physicians-investigators (CGI-EL Scale) the combination of the anti- and protussive activities in one drug to be efficient and absolutely safe for the chilgren. The therapeutic efficacy in the patients of the rengalin group was higher in 3 days (2.1 ± 0.5 numbers) and even in 7 days (2.7 ± 0.5 numbers). The results value in the patients of the sinekod group being 1.8 ± 0.4 and 2.5 ± 0.6 numbers (one-wayANOVA for repeated estimates ANOVA: Visit - F(1/138) = 146, p < 0.0001, TREATMENT--F(1/138) = 9.0, p = 0.003). The factor of the side effects in the patients of the rengalin group was zero (no side effects due to the treatment were recorded in the patients), whereas in the patients treated with sinekod for 3 days the respective value was 0.1 ± 0.3 (true superiority of rengalin by the ANOVA data. TREATMENT--F(1/138) = 4.7, p = 0.03). The efficacy factor of the rengalin was also in its favour (ANOVA: Visit--F(1/138) = 182, p < 0.0001, TREATMENT--F(1y138) = 7.3, p = 0.008). In the patients treated with rengalin there were defected no deviations in the biochemical and general clinical analyses of blood and urine, no adverse reactions characteristic of antitussive drugs of the action. 100-percent adherence to the therapy was stated. CONCLUSION: He antitussive effect of rengalin in the treatment of frequent dry day-time and night-time cough was observed earlier and proved to be comparable with that of butamirate (sinekod). Rengalin prevented significant exudation and viscid expectoration in many patients, promoted rapid residual in the patients with dry cough and the patients recovery. The use of rengalin for 3 days significantly lowered the percentage of the patients requiring treatment with mucolytics at the subsequent stages of ARI.

[Assessment of equivalence of the original tamsulosin and its generics].

Generics constitute a significant part of the modern pharmaceutical market. The use of generics in the case of their equivalence to the original drug allows to reduce the burden of health care costs. Often, however, the quality of generics does not match that of the original drug. The results of study suggest that the investigated generics of tamsulosin may not be fully recognized as pharmaceutically equivalent to the original drug.