Efficacy of Anaferon for Children in the Treatment of Influenza and Acute Respiratory Viral Infections in Children

Phase 4

Completed

Conditions: Influenza and Acute Respiratory Viral Infections

Interventions: Drug: Anaferon for Children

Registration Number: NCT02072174

Lead Sponsor: Materia Medica Holding

Brief Summary: The purpose of this study is:

• To obtain additional data on therapeutic efficacy of Anaferon for children in the treatment of influenza and acute respiratory viral infections in children

Detailed Description: The study will enroll outpatient subjects of both sexes aged 3-12 years with clinical manifestations of influenza/Acute Respiratory Viral Infections (ARVI), including fever

≥ 38.0°С having an appointment with a doctor within the first day after the illness onset.

Тhe physician will collect medical history information, perform an objective examination, record the concomitant therapy, and obtain nasal swab specimens for a rapid diagnostic influenza test. If the swab is positive, the doctor shall obtain swab specimens from the nasal cavity and oropharynx (nasopharyngeal swab) for a subsequent real time reverse transcription-polymerase chain reaction (RT-PCR) to determine the viral load of influenza A and/or B virus. If the swab is negative for influenza the doctor shall collect a nasopharyngeal swab for a subsequent PCR test for other respiratory viruses.

If inclusion criteria are met and exclusion criteria are absent at visit 1 (Day 1), the patient will be enrolled in the trial and randomized into one of the two groups: group 1 patients will take Anaferon for children following a 5-day regimen; group 2 patients will receive Placebo using the Anaferon for children 5-day regimen. The parent/adopter of patient will receive a diary where they should record the child's axillary temperature data in the morning and evening, and score the severity of symptoms.

The subject will be monitored for 14 days (screening, randomization - 1 day, treatment - 5 days, follow-up - 1 day; late-scheduled phone "visit" - day 14).

At Visits 2-4, the physician will document objective examination data; obtain nasopharyngeal swabs from subjects with positive influenza tests for subsequent RT-PCR to determine the viral load and its reduction in the course of treatment; monitor the prescribed and concomitant therapy, and check the patient's diary data. The phone "visit" will be made to elicit information from the parents regarding the patient's general health, presence/absence of secondary bacterial/viral complications, and use of antibacterial drugs.

Interim statistical analysis is stipulated by the study protocol. Interim analysis will be performed using the data obtained from the examination and treatment of the protocol-defined number of patients who completed the study. Based on the expected effect, the minimum required Particular Per Protocol (pPP) sample size will be 254 patients (127 subjects in each group - Anaferon for children and Placebo).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 569

Inclusion Criteria

Patients of both sexes aged 3-12 years inclusively.
Diagnosis of influenza/ARVI according to physician's examination: body temperature ≥ 38.0°C at the time of examination + symptom score ≥ 4 (at least 1 systemic symptom ≥2 and 1 nasal/throat/chest symptom ≥2 or several symptoms ≥ 1 score).
The first 24 hours from the beginning of manifestations of influenza/ARVI.
The possibility to start therapy within 24 hours from the first symptoms of ARVI.
Availability of a patient information sheet (Informed Consent form) for parents/adoptive parents for participation in the study signed by one of the parents/adoptive parents.

Exclusion Criteria

Suspected pneumonia, bacterial infection or severe disease requiring antibacterial products (including sulfanilamides) starting from the first day of the disease.
Clinical symptoms of severe influenza/ARVI requiring hospitalization.
Suspected initial manifestations of the diseases having the symptoms similar to the ones of influenza/ARVI (other infectious diseases, influenza-like syndrome at debut of systemic connective tissue diseases, oncohematological and other diseases).
Medical history of primary and secondary immunodeficiencies: а) lymphoid system immunodeficiencies (Т-cell and/or B-cell, immunodeficiencies with predominant antibody deficiency); b) phagocytic deficiencies; c) complement factor deficiency; d) combined immunodeficiencies including AIDS secondary to HIV-infection; toxic, autoimmune, infectious, radiation panleukopenic syndrome; systemic lymphocytopenic syndrome; polyclonal lymphocytic activation syndrome; postsplenectomic syndrome; congenital asplenia; immune complex pathological syndrome associated with infectious, autoimmune and allergic diseases.
Medical history of sarcoidosis.
Oncology.
Exacerbation or decompensation of chronic diseases affecting ability to participate in the clinical study.
Medical history of polyvalent allergy.
Allergy/intolerance to any of the components of medications used in the treatment.
Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
Intake of medicines listed in the section "Prohibited concomitant therapy" within 1 month prior to the inclusion in the study.
Drug addiction, alcohol consumption at more than 2 alcohol units per day by the subject's parents/adoptive parents.
Mental diseases of the subject, parents/adoptive parents.
Subjects whose parents/adoptive parents, according to the investigator's point of view, will not follow the observation requirements during the study or study product dosing regimen.
Participation in other clinical studies within 3 months prior to the inclusion in the study.
Parent/adoptive parent of the subject is related to the investigator team of medical facility directly involved in the study or is a close relative of the investigator. Close relatives include spouse, parents, children or brothers (sisters) regardless of whether they are biological or adoptive ones.
Parent/adoptive parent of the subject is working in OOO "NPF "Materia Medica Holding", i.e. is the company official, temporary contract worker or an appointed official responsible for the study or their close relatives.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anaferon for Children	Anaferon for Children	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. From day 2 through 5, one tablet is administered three times daily.
Placebo	Anaferon for Children	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. From day 2 through 5, one tablet is administered three times daily.

Primary Outcome Measures

Name	Time	Method
Average Illness Duration	From the time of randomization until the time of recovery/improvement (days 1-14)	Disease duration is assessed until recovery or significant improvement. Average illness duration is defined as the interval between the start of the trial treatment and the start of the first 24-hour period in which the non-specific symptoms and nasal/ throat/ chest symptoms improve to "absent" or "mild" (Total Symptom Score of severity had decreased to ≤2 points) and body temperature returns to 37.2°C or below. Based on patient diary data.

Secondary Outcome Measures

Name	Time	Method
Number of Intakes of Antipyretics	on days 1-5 of therapy	Number of Intakes of Antipyretics based on patient diary data
Percentage of Patients With Recovery/Improvement in Health	on days 2, 3, 4 and 5 of the treatment	Based on Days 2, 3, 4 and 5 of observation treatment (according to the patient's diary), on days 3 and 5 of therapy (according to physician's objective examination).
Changes in Body Temperature	baseline and days 2, 3, 4 and 5 of observation treatment	Changes in Body Temperature Based on Patient Diary Data
Percentage of Patients With Normal Body Temperature (≤37.0ºС)	on days 2, 3, 4 and 5 of observation treatment	Based on the patient diary data. Axillary temperature (morning and evening) decline to or below 37.0 ºС.
Percentage of Patients With Exacerbation of the Disease Course	14 days of observation treatment	The development of disease complications requiring antibiotics drugs or hospitalization
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score.	on days 2-6 of observation treatment	Total Symptom Score is based on the severity of each Influenza / Acute Respiratory Viral Infection symptom. Total Symptom Score includes 13 symptoms: body temperature, non-specific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), nasal/throat/chest symptoms. The severity of non-specific and nasal/throat/chest symptom is scored on a symptom severity scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). Minimum score=0; maximum score=39. The severity of symptoms is recorded by the doctors on the case record form on days 3, 5 and by parents/adopter on a diary card twice a day on days 2-6.
Assessment of the Severity of Influenza Virus / Acute Respiratory Viral Infection Using the "Area Under the Curve" for an Overall Symptom Assessment	on days 1-7 of observation (based on days 1-7 on the patient diary data; on days 1, 3, 5 and 7 of observation - according to physician's objective examination)	Total Symptom Score is based on the severity of each disease symptom. The TSS includes 13 symptoms: body temperature/fever, non-specific 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). Minimum score=0; maximum score=39. The area under the curve 1 = on days 1, 3, 5 and 7 on the results of doctor's examination The area under the curve 2 = based on days 1-7 on the patient diary data
Change in Viral Load During the Treatment and Follow-up Periods	on days 1, 3, 5, 7 of observation treatment	Viral load is evaluated in subjects with positive influenza A and B tests. Virus load \[log10 copies influenza А/В RNA per 1 mL\] in nasal and pharyngeal swabs is determined using real-time PCR on days 1, 3, 5 and 7.

Trial Locations

Locations (27): State Budgetary Educational Institution of Higher Professional Education "Yaroslavl State Medical Academy"
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Yaroslavl, Russian Federation
Municipal Health Care Institution "City Child Health Clinical Polyclinic №10"
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Minsk, Belarus
State Budgetary Educational Institution of Higher Professional Education "St. Petersburg State Pediatric Medical Academy" of Ministry of Health of Russian Federation
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St. Petersburg, Russian Federation
City Child Health Clinical Polyclinic №17
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Minsk, Belarus
State Budgetary Educational Institution of Higher Professional Education ''Novosibirsk State Medical University'' of Ministry of Health of Russian Federation
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Novosibirsk, Russian Federation
Clinic of State Budgetary Institution "Research Institute of nutrition" of the Russian Academy of Medical Sciences
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Moscow, Russian Federation
State Health Care Institution "Child Health City Hospital №22"
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St. Petersburg, Russian Federation
Yaroslavl State Medical Academy
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Yaroslavl, Russian Federation
Public institution "Zaporizhzhya city multidisciplinary children's hospital №5"
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Zaporozh'ye, Ukraine
City Child Health Clinical Polyclinic №13
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Minsk, Belarus
State Budgetary Educational Institution of Higher Professional Education " Nizhny Novgorod State Medical Academy" of Ministry of Health of Russian Federation
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Nizhnij Novgorod, Russian Federation
State Budgetary Educational Institution of Higher Professional Education "Rostov State Medical University"
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Rostov-na-Donu, Russian Federation
Co.Ltd "Clinic Allergomed"
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St. Petersburg, Russian Federation
State Budgetary Educational Institution of Higher Professional Education " Yaroslavl State Medical Academy" of Ministry of Health of Russian Federation
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Yaroslavl, Russian Federation
St. Petersburg State Budgetary Health Care Institution "Сity Polyclinic №44"
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St. Petersburg, Russian Federation
Limited Liability Company "Alliance Biomedical-Russian group"
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St.Petersburg, Russian Federation
Municipal Health Care Institution "City Child Health Clinical Polyclinic №5"
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Perm, Russian Federation
Bashkir State Medical University of Ministry of Health of Russian Federation
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Ufa, Russian Federation
Vinnytsya M.I. Pyrogov National Medical University
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Vinnytsya, Ukraine
Russian National Research Pirogov Medical University
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Moscow, Russian Federation
State Budgetary Institution of Health, "Children's City Hospital № 9 named after G.N. Speranskii"
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Moscow, Russian Federation
State Budgetary Educational Institution of Additional Professional Education "Russian Russian Medical Academy of Postgraduate Education" of Ministry of Health of Russian Federation
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Moscow, Russian Federation
State Educational Institution of Higher Professional Education "Moscow State Medical Academy named after I.M. Sechenov"
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Moscow, Russian Federation
St. Petersburg State health institution " City Child Health Polyclinic № 45"
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St. Petersburg, Russian Federation
State Budgetary Educational Institution of Higher Professional Education "Yaroslavl State Medical Academy
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Yaroslavl, Russian Federation
Russian National Research Medical University named after N.I. Pirogov
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Moscow, Russian Federation
Russian National Research Medical University
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Moscow, Russian Federation