RESUMO
A prospective, two-center, open-label, randomised clinical trial assessing the efficacy and tolerability of treatment strategies involving the administration of Ergoferon and Kagocel in paediatric outpatients aged over 3 years was carried out. The study was conducted with the objective of obtaining a comprehensive evaluation of drug-based therapy options used in routine paediatric practice to treat acute respiratory infections (ARI) during the 2012-2013 epidemic season. A total of 90 ARI-diagnosed child-age patients able to initiate treatment within 48 hours of infection onset entered the trial. Nine participants were excluded from final analysis due to protocol violation. The patients were randomised into 2 groups (Ergoferon (group 1): 41 subjects and Kagocel (group 2): 40 subjects) with similar distribution of sex, age, baseline clinical data, and time of treatment initiation. The study involved clinical assessment including daily body temperature monitoring (morning/evening measurements) and three PCR assays of nasal swabs. At visits 2 and 3, the number of patients achieving normal body temperature (primary endpoint) was estimated and severity of intoxication and catarrhal syndromes and individual symptoms as well as the rate of virus elimination were evaluated. In addition, visit 3 included the assessment of the volume and cost of treatment in conjunction with clinical benefit and treatment safety/tolerability (as judged by the physicians and parents). By the end of the first day of treatment, the number of children with body temperature of above 38 C was significantly decreased as compared to the morning baseline (p=0.008) and respective values in group 2 (p=0.02). At visit 2 (treatment day 4), the state of 80% of patients in either group was assessed as satisfactory and over 70%, respectively, could maintain normal body temperature throughout the day. Total intoxication scores were reduced by 7-10 points and were less than 9 in 100% of patients. The overall scores of catarrhal symptoms were 2.5-3 points lower than the baseline levels and were less or equal to 9 in 80-90% of children in either group. By visit 3, 'satisfactory' health assessments were reported for 95% of patients in respective groups. Signs of catarrh were completely resolved in 37% of participants in group 1 and 15% in group 2 (p=0.03). At the same point, 66% of patients in group 1 and 55% in group 2 were observed to have no (or isolated or negligible) signs of infection which did not require continuation of treatment (p>0.05). The percentage of children achieving recovery was 3 times greater in group 1 than in group 2 (p=0.01). No bacterial complications were presented by any of the study subjects. The severity of individual symptoms of catarrh varied significantly between the groups as observed at visits-2 and 3. At visit 2, 92% of subjects in group 1 had no or only minor (requiring no drug intervention) obstruction breathing through the nose and 26.8% reported no nasal blockage (p=0.04), while the latter was observed to persist in 60% of children in group 2 (p<0.001). By the time of visit 2, the number of patients attaining complete resolution of serous nasal discharge was increased by more than 2.5 in group 1 - up to 31.7% (p=0.01), while this number in group 2 was 17.5% and did not significantly differ from the baseline level (visit 1, p=0.4). There were also differences in cough pattern changes between the groups, i.e. the dry cough was converted into a productive cough in 44% of subjects in group 1 vs. 20% in group 2 (p=0.06). As reported at visit 3, the number of patients having no difficulty breathing nasally was 88% in group 1 vs. 38% in group 2 (p=0.008). The percentage of children exhibiting complete resolution of cough as observed at visit 3 was 2 times higher in group 1 then in group 2 (respectively, 24% vs.12%; p>0.05). No adverse events related to medications used as part of the treatments administered were reported during the study. The mean CGI scores (overall safety and efficacy index) were similar between the groups: 3.5±0.6 in group 1 vs. 3.3±0.6 in group 2 (p=0.25). The percent of maximum scores was 51% and 38% in groups 1 and 2, respectively. Mean efficacy scores in patient groups were 3.9±0.6 and 3.6±0.6, respectively (p=0,036), with respective tolerability ratings represented by scores of 4.3±0.7 and 3.8±0.5 (p=0,002). The mean number of drugs prescribed was 4.7±1.0 in group 1 vs. 6.0±1.3 in group 2 (p<0.001). The percent of cases where not more than 4 medications were administered to a subject and the number of occasions when a child was prescribed to receive 6 drugs or over varied significantly between the groups and were 46% vs.10% and 27% vs. 70% , respectively (p<0.001). Similarly, there were differences in the duration of treatment with drugs belonging to distinct pharmacological groups: 6.0±1.4 vs.8.8±1.5 days (p<0.05) for antihistamines; 6.1±2.0 vs. 7.1±2.4 days (p=0.15) for decongestants; 6.0±1.1 vs.7.1±2.4 days (p=0.07) for mucolytics; and 6.9±1.4 vs. 8.4±2.3 days (p=0.04) for locally-acting anti-inflammatory and antiseptic agents, as reported for group 1 vs. group 2, respectively. The mean treatment cost per ARI case was 1353±320.2 rubles in group 1 compared to 1768±491.0 rubles in group 2 (p=0.008). Swab specimens from 76 children (41 subjects from groupl and 35 from group 2) were tested using PCR. Baseline specimens were mostly positive for rhinoviruses, influenza A(H3N2) virus, and parainfluenza virus types 2 and 3. By visit 2, virus elimination was demonstrated for 46% of cases in group 1 and 23% in group 2 (p<0.03). By the time of visit 3, the tests were indicative of virus removal for 66% of children in group 1 and 49% in group 2. Thus the antiviral drugs used as part of combination treatment of ARIs were shown to enable fast recovery and prevent the development of bacterial complications, proving to be well-tolerated. Patients in the Ergoferon group demonstrated faster resolution of ARI symptoms and shorter elimination of respiratory viruses, had less need for additional medications, and.required 23% less spending on treatment, resulting in a greater number of favorable assessments of.Ergoferon by both the physicians and parents.
RESUMO
A randomized double-blind controlled study was carried out to evaluate changes in the clinical presentation of acute obstructive bronchitis in preschool children using antiviral, anti-inflammatory therapy. The study enrolled 54 subjects'(aged 3-6 years old) hospitalized with verified diagnosis of acute obstructive bronchitis. Their parents had given their informed consent for participation. Group 1 (n=26) received etiotropic therapy with the drug having complex antiviral, anti-inflammatory and antihistamine effect (Ergoferon), group 2 (n=28) received placebo. Meanwhile all children received complex therapy of ARI. To evaluate therapeutic efficacy the following parameters were compared: time to elimination of the clinical manifestations of the disease; extent of alleviation of the key symptoms, incidence of wheezing episodes and complications. RESULTS: According to PCR, rhinoviruses prevailed in both groups in oropharyngeal swabs (31% in.group 1 and 57% in group 2); furthermore, RNA of influenza B virus, respiratory syncytial virus, parainfluenza virus types 2 and 4 and metapneumovirus were also detected; 3 children in each group simultaneously had RNA of various viruses; no differences between the groups were observed. In group 1 average duration of increased body temperature (morning measurement) was 1.6 (1.4-1.9)±0.6 days, respectively, and all children reached normal values of morning and evening body temperature by the end of 3-day therapy. In group 2 morning body temperature reached normal values on types 2.7 (2.1-3.3)±1.2 days, respectively (U-test, P==0.002), while complete normalization in all children took place on day 6 of the follow-up. Area under curve for daily body temperature was statistically lower in group 1: 514.3 (513.8-514.9)±1.4 ('C X days) vs. 516.3 (515.1-517.5)±2.5(*C X days) in group 2 (U-test, P=0.002). Intoxication in group 1 was eliminated within 2.8 (2.5-3.1)±0.80 days on average, in group 2 - within 4.5 (4.1-4.8)±0.96 days (P<0.001). Intensity of catarrhal symptoms (nasal congestion, rhinitis, cough) resolved faster in group 1 (P<0.05). Average elimination term for catarrhal symptoms was 6.0 (5.7-6.3)±0.8 days vs. 9.0 days for groups 1 and 2 (P<0.001), respectively. Wheezing resolved within 4.1 (4.0-4.2)±0.3 days on average in group 1 and within 6.9 (6.7-7.0)±0.4 days in group 2 (P<0.001). Despite the treatment, eight children in group 2 showed moderate reinforcement of wheezing within the first 3-4 days of therapy, 3 of them had body temperature increased to subfebrile values requiring antibacterial treatment. Neither of children in group 1 had any bacterial complications or reinforced wheezing. All children from group 1 had complete recovery on day 8. Neither of subjects recovered completely on day 9 in group 2. Average recovery term in group 1 was 6.0 (5.7- 6.3)±0.8 days vs. 9.0 days in group 2 (P<0.001). No adverse effects associated with the medicinal products were recorded during the study. Average rating of therapeutic efficacy by the investigator using CGI scale was 3.7 (3.5-3.8)±0.49 scores in group 1 vs. 2.6 (2.3-2.9)±0.69 scores in group 2 (P<0.005). Rating of wheezing therapy efficacy was similar: 3.7 (3.4- 3.9)±0.57 and 2.2 (1.7-2.7)±1.29 for groups 1 and 2, respectively. Safety of the products according to CGI scale reached maximum in both groups. Parents' rating of the treatment in group 1 was 50% higher as compared to group 2: 3.6 (3.4- 3.8)±0.57 scores and-2.5 (1.8-2.9)±1.31 scores (P<0.005). CONCLUSION: Ergoferon in complex therapy of acute obstructive bronchitis in preschool children ensures rapid therapeutic effect including elimination of wheezing symptoms, prevention of bacterial complications, wheezing progression and is well tolerated by the subjects.
RESUMO
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.
