Clinical Trial of Safety and Clinical Efficacy of Ergoferon in Liquid Dosage Form in Treatment of Acute Upper Respiratory Tract Infections in Children

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is: to assess safety of the liquid dosage form of Ergoferon for treatment of acute upper respiratory tract infections in children; to assess clinical efficacy of the liquid dosage form of Ergoferon for treatment acute upper respiratory tract infections in children.

Detailed Description
-----------------
The overall duration of a patient's participation in the trial is 6 days (screening/randomization, therapy onset - day 1; study therapy period - 5 days; follow-up period-1 day).

Official Title
-----------------
Multicentre Double-blind Placebo-controlled Parallel-group Randomized Clinical Trial of Safety and Clinical Efficacy of Ergoferon in Liquid Dosage Form in Treatment of Acute Upper Respiratory Tract Infections in Children

Conditions
-----------------
Acute Upper Respiratory Tract Infections

Intervention / Treatment
-----------------
* Drug: Ergoferon
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of both sexes aged over 3 years and under 18 years. Patients who consulted a doctor within 24 hours after the onset of acute respiratory infection (body temperature no less than 38.0°C when visiting a doctor + intensity of symptoms ≥ 4 scores (presence of at least 1 general symptom ≥ 2 scores and 1 nasal/ throat/ chest symptom ≥ 2 scores or greater number of symptoms with the intensity≥1 score) during seasonal morbidity. The possibility to start therapy within 24 hours after the onset of the first symptoms of acute respiratory infection. Usage of contraceptive methods by sexually active teenagers of both sexes during the trial and within 30 days after ending of the participation in the trial. Availability of information sheet (Informed Consent form) for parents/adopters of patient for participation in the clinical trial, Version 2.1 or Version 2.2, signed by one parent/adopter of patient. For patients over 14 years - availability of information sheet (Informed Consent form) for participation in the clinical trial, Version 2.1 or Version 2.2, signed by a patient and one parent/adopter of patient. Exclusion Criteria: Suspected bacterial infection or presence of a severe disease requiring use of antibacterial drugs (including sulfanilamides). Suspected initial manifestations of diseases that have symptoms similar to acute respiratory infection (other infectious diseases, influenza-like syndrome at the onset of systemic connective tissue disorders, oncohematology and other pathology). Medical history of primary and secondary immune deficiency: a) lymphoid system immunodeficiency (T-cell and /or B-cell immunity chain, immunodeficiency with predominant antibody deficiency); b) phagocyte deficiency; c) complement factors deficiency; d ) combined immunodeficiency including AIDS induced by HIV infection; toxic, autoimmune, infectious, radial panleukopenia syndrome; general lymphocytopenia syndrome; syndrome of lymphocyte polyclonal activation; postsplenectomia syndrome; congenital asplenia; syndrome of immune complexes pathology associated with infectious, allergic and autoimmune diseases. Medical history of sarcoidosis. Oncological diseases. Exacebration or decompensation of chronic diseases affecting the patient's ability to participate in the clinical trial. Medical history of polyvalent allergy. Allergy/ intolerance to any of the components of medications used in the treatment. Impaired glucose tolerance, diabetes mellitus. Hereditary fructose intolerance (as the study drug contains maltitol). Intake of medicines listed in the section Prohibited concomitant treatment for 1 month prior to the inclusion in the trial. Pregnancy, unwillingness of sexually active female patients to use of contraceptive methods during the study. Drug addiction, alcohol usage in the amount 2 units of alcohol per day on the part of patient's parents/adopters. Mental disorders of patient or of patient's parents/adopters. Patient's parents/ adopters, who from investigator's point of view, will fail to comply with the observation requirements of the trial or with the intake regimen of the investigated medicines. Participation in other clinical trials in the course of 3 months prior to the inclusion in the trial. Patient's parent/adopter is related to the research personnel of the investigative site, who are directly involved in the trial or are the immediate relative of the researcher. The immediate relatives includes husband/wife, parents, children or brothers (or sisters), regardless of whether they are natural or adopted. Patient's parent/adopter works for OOO NPF Materia Medica Holding (i.e. is the company's employee, temporary contract worker or appointed official responsible for the carrying out the research) or the immediate relative.

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ergoferon (5 ml 3 times a day)<br> | Drug: Ergoferon<br>* Safety and Efficiency of liquid dosage form<br>|
| Placebo Comparator: Placebo (5 ml 3 times a day)<br> | Drug: Placebo<br>* Safety and Efficiency of liquid dosage form<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Recovery/Improvement in Health on Days 2, 3 and 4 of Observation (Based on Patient Diary Data) | Based on the data mentioned in a patient's diary | On day 2, 3 and 4 of observation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dynamics of Fever (Changes in Body Temperature on 2, 3, 4, 5 Days of Observation in Comparison With the Baseline) |  | baseline and days 2, 3, 4 and 5 of observation | 
| Percentage of Patients With Normal Body Temperature (≤37.0ºС) | Axillary temperature (morning and evening) decline to or below 37.0 ºС | On day 2, 3, 4, 5 of observation | 
| Severity of Clinical Manifestations of Acute Respiratory Infection (ARI) by Total Symptom Score on Day 3 of Observation (Based on the Results of Pediatrician's Examination) and on Days 2, 3, 4 and 5 of Observation (Based on Patient Diary Data) | The Total Symptom Score (TSS) was based on the severity of each of acute respiratory infection (ARI) symptom. The TSS includes 13 symptoms: Body temperature / fever, Non-specific ARI symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), Nasal/Throat/Chest symptoms (Runny nose, Nasal congestion, Sneezing, Sore throat, Hoarseness, Cough, Chest pain/Tightness of the chest). The severity of Non-specific and Nasal/Throat/Chest symptom was scored on a symptom severity scale (0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). The Fever was scored on a symptom severity scale 0 = no symptom (≤37,30С); 1 = mild symptom (37,4-38,00С); 2 = moderate symptom (38,1-39,00); 3 = severe symptom (≥39,10С). Minimum score=0; maximum score=39. The severity of ARI symptoms was recorded: 1) by the doctors on the case record form on Day 3; 2) by one of the patient's parents/adopter on a diary card twice a day (morning and evening) on Days 2-5. | on Days 2, 3, 4, 5 of Observation | 
| Duration of Acute Respiratory Infection Symptoms (Fever, Non-specific Symptoms and Nasal/ Throat/ Chest Symptoms) Based on Patient Diary Data | Acute respiratory infection (ARI) symptoms include 13 symptoms: Body temperature / fever, Non-specific ARI symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), Nasal/Throat/Chest symptoms (Runny nose, Nasal congestion, Sneezing, Sore throat, Hoarseness, Cough, Chest pain/Tightness of the chest). The ARI symptoms was recorded by one of the patient's parents/adopter on a diary card twice a day (morning and evening) on Days 1-5. | baseline and days 2, 3, 4 and 5 of observation | 
| Severity of the Disease Within 6 Days Was Assessed Using the Area Under the Curve for the Total Symptom Score (TSS) | The Total Symptom Score (TSS) was based on the severity of each of acute respiratory infection (ARI) symptom. The TSS includes 13 symptoms: Body temperature / fever, Non-specific ARI symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), Nasal/Throat/Chest symptoms (Runny nose, Nasal congestion, Sneezing, Sore throat, Hoarseness, Cough, Chest pain/Tightness of the chest). The severity of Non-specific and Nasal/Throat/Chest symptom was scored on a symptom severity scale (0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). The Fever was scored on a symptom severity scale 0 = no symptom (≤37,30С); 1 = mild symptom (37,4-38,00С); 2 = moderate symptom (38,1-39,00); 3 = severe symptom (≥39,10С). Minimum score=0; maximum score=39. The severity of ARI symptoms was recorded: 1) by the doctors on the case record form on Days 1, 3, 6; 2) by one of the patient's parents/adopter on a diary card twice a day (morning and evening) on Days 1-5. | On days 1-6 of observation | 
| Number of Intakes of Antipyretics if Indicated | Based on data mentioned in a patient's diary | On day 1, 2, 3, 4 and 5 of the treatment | 
| Percentage of Patients With Exacerbation of the Disease Course | The development of disease complications requiring antibiotics administration or hospitalization | On days 1-6 of observation |