Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children

Study Overview
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Brief Summary
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The international multicenter double-blind placebo-controlled randomized clinical study in parallel groups.The objective of this study is to obtain additional data on the efficacy and safety of Ergoferon in the treatment of acute respiratory viral infections (ARVI) in children aged from 6 months to 6 years old.

Detailed Description
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Study design: international, multicenter double-blind placebo-controlled randomized clinical study in parallel groups. The study will enroll patients of either gender aged from 6 months to 6 years old with clinical manifestations of ARVI within the first days after the onset of the disease. Patients will be included evenly (1:1 ratio) in accordance with the age group: 6 months - 3 years 11 months 29 days; 4 years - 6 years 11 months 29 days. Signed information sheet for parents/adopters (inform consent form) will be obtained from all participant's parents/ adopters prior to the screening procedures. Medical history, thermometry, patient examination by the doctor, assesment of ARVI symptoms severity and nasopharyngeal swabswill be performed at screening visit (Day 1). If the inclusion criteria are met and exclusion criteria are absent, the patient is included in the study. Nasopharyngeal swabs will be analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) to identify the most common respiratory viruses, including (1) Influenza A virus; (2) Influenza B virus; (3) Influenza A (H1N1)pdm; (4) Human metapneumovirus; (5) Human respiratory syncytial virus; (6) Human rhinovirus; (7) Human adenovirus; (8) Human bocavirus; (9) Human parainfluenza virus 1; (10) Human parainfluenza virus 2; (11) Human parainfluenza virus 3; (12) Human parainfluenza virus 4; (13) Human coronavirus OC43; (14) Human coronavirus 229E; (15) Human coronavirus HKU1; (16) Human coronavirus NL63. The patients are randomized into one of two groups: the 1st group patients will take Ergoferon according to the dosage regimen for 5 days; the 2nd group patients will take Placebo according to the dosage regimen of Ergoferon for 5 days. Patient's parents/ adoptive parents are provided with diares, where daily in the morning and at hight they record oral temperature (measured by a digital thermometer provided by Sponsor), symptoms of ARVI (according to the 4-points scale), administered drug and concomitant therapy. The doctors instruct parents/ adoptive parents how to fill in the diaries; the first scores of ARVI symptoms severity and oral temperature are made by doctors together with the parents/adoptive parents. Patients are observed up for 14 days (screening and randomization - up to 1 day, therapy for 5 days, follow-up from 6 to 10 days; delayed telephone visit - on day 14). During the observation period, two visits are planned (at home or at the medical center) on day 3 (Visit 2) and day 6 (Visit 3). If patients still have any symptoms of ARVI/ complications of ARVI, then an additional (unscheduled) Visit 4 is provided on Day 10 of the observation (at the medical center). During Visits 2, 3 (4), doctors carry out an physical examination, record dynamics of ARVI symptoms and concomitant therapy, check patient's diaries, which parents/adoptive parents return back at Visit 3 or 4. At Visit 3 (after 5 days of therapy) compliance with the treatment is additionally assessed. A telephone visit (Visit 5, Day 14 ± 1) is carried out to interview parents about the patient's condition, presence/ absence of complications, and possible use of antibiotics. During the study, symptomatic therapy and therapy for underlying chronic conditions are allowed with the exception of the drugs indicated in the section Prohibited Concomitant Therapy.

Official Title
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International Multicenter Double-blind Placebo-Controlled Parallel-Group Randomized Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children

Conditions
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Acute Respiratory Viral Infections

Intervention / Treatment
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* Drug: Ergoferon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both genders aged from 6 months to 6 years old. ARVI based on medical examination: oral temperature of at least 38.0°C at examination + total symptom severity ≥5. The first 24 hours after ARVI onset. Seasonal raise in ARVI incidence. Availability of signed information sheet for parents/adopters(Informed Consent Form) for participation in the clinical trial. Exclusion Criteria: Suspected pneumonia or bacterial infection (e.g. meningitis, sepsis, otitis media, urinary tract infection, etc.) requiring a prescription of antibacterial product from the first day of the disease. Suspected initial manifestations of diseases with symptoms similar to ARVI at onset (other infectious diseases, flu-like syndrome at the onset of systemic diseases of connective tissue, oncohaematological and other diseases). Clinical symptoms of severe influenza infection/ARVI requiring hospitalization. Medical history of primary and secondary immunodeficiency; oncologic conditions. Aggravation or decompensation of chronic disease (diabetes mellitus, cerebral palsy, cystic fibrosis, primary ciliary dyskinesia, bronchopulmonary dysplasia, malformations of the respiratory and ETN organs/ear, throat, mouth, tongue, larynx, trachea, neck and salivary and thyroid glands, etc.) which affect the patient's ability to participate in the clinical study. Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia. Allergy/hypersensitivity to any components of the drug product used in the therapy. Course administration of the drug products specified in the section Prohibited Concomitant Therapy within two weeks prior to inclusion in the study. Patients whose parents/adoptive parents will not fulfil the requirements during the study or follow the order of administration of the studied drug products from the investigator's point of view. Participation in other clinical trials within 3 months prior to the enrollment in this study. The patient's parent/adoptive parent is a study specialist at the centre and is directly involved in the study or is an immediate family member of the investigator. Spouses parents, children or siblings, regardless of whether they are siblings or adopted are considered immediate family members. The patient's parent/adoptive parent works at OOO NPF MATERIA MEDICA HOLDING, i.e. they are employees of the Company, temporary employees on a contract basis or appointed official responsible for conduction of the study or their immediate family members.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ergoferon<br>Tablet for oral use, 1 tablet per intake (outside a meal/feeding). On day 1, five tablets are taken in the first 2 hours (one tablet every 30 min), followed by three more tablets regularly spaced during the rest of the day (total 8 tablets). From day 2, one tablet is taken every 8 hours. The drug is administered outside a meal (in the interval between meals or 15 minutes before meal or fluid intake). Keep the tablet in the mouth, without swallowing, until completely dissolved. For young children (aged 6 months to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature. The therapy lasts for 5 days. | Drug: Ergoferon<br>* For oral use.<br>|
| Placebo Comparator: Placebo<br>Placebo using Ergoferon scheme. | Drug: Placebo<br>* For oral use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Alleviation of All ARVI Symptoms. | Based on patient diary data. Criteria of alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome. | 14 days of observation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Normalization of Body Temperature. | Based on patient diary data. Oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period). | 14 days of observation. | 
| Time to Alleviation of Flu-like Nonspecific Symptoms. | Based on patient diary data. Absence of flu-like nonspecific symptoms/presence of one mild flu-like nonspecific symptom. | 14 days of observation. | 
| Time to Alleviation of Respiratory Symptoms. | Based on patient diary data. Absence of respiratory symptoms/presence of one mild respiratory symptom. | 14 days of observation. | 
| Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. | Based on patient diary data. The total score (TS) ranges from 0 to 30 consisting of 4 flu-like nonspecific (decreased activity/weakness, poor appetite/refusal to eat, sick appearance, sleep disturbance) and 6 respiratory (runny nose, stuffy nose/nasal congestion, sneezing, hoarseness, sore throat, cough) symptoms according to the 4-point scale for each symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome. | On days 2-6 of the observation period. | 
| ARVI Severity. | Based on the area under the curve of TS for days 2-6, according to the patient diary. The total score (TS) will be calculated based on the severity of each ARVI symptom (sum of 11 symptoms = body temperature, flu-like nonspecific symptoms (4 symptoms) and respiratory symptoms (6 symptoms) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TS the absolute oral temperature values, measured in degrees Celsius, will be converted into relative units (or points), given the following gradations: ≤37.5С = 0 point; 37.6-38.1C = 1 point; 38.2-38.8C = 2 points; ≥38.90С = 3 points. For total score minimum and maximum scores are 0 and 33, where higher values represent a worse outcome. | On days 2-6 of the observation period. | 
| Percentage of Recovered Patients. | Based on patient diary data. Criteria of recovery/alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale for each flu-like nonspecific and respiratory symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom). | On days 2-6 of the observation period. | 
| Rates of Antipyretics Use Per Patient. | Based on patient diary data. The number of intakes of prescribed antipyretics. | On days 1- 5 of the treatment period. | 
| Percentage of Patients With Worsening of Illness. | Based on patient diary data. The disease worsening: ARVI complications, including those requiring antibiotics; hospitalization). | 14 days of observation peiod. |