Clinical trial NCT02072174: Efficacy of Anaferon for Children in the Treatment of Influenza and Acute Respiratory Viral Infections in Children
Official title: International Multicenter Double-blind Placebo-controlled Randomized Parallel Group Clinical Trial of Efficacy of Anaferon for Children in the Treatment of Influenza and Acute Respiratory Viral Infections in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza and Acute Respiratory Viral Infections
Lead sponsor: Materia Medica Holding
Sponsor class: INDUSTRY
First posted: 2014-02-26
Enrollment: 569
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Patients of both sexes aged 3-12 years inclusively.
2. 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).
3. The first 24 hours from the beginning of manifestations of influenza/ARVI.
4. The possibility to start therapy within 24 hours from the first symptoms of ARVI.
5. 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:

1. Suspected pneumonia, bacterial infection or severe disease requiring antibacterial products (including sulfanilamides) starting from the first day of the disease.
2. Clinical symptoms of severe influenza/ARVI requiring hospitalization.
3. 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).
4. 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.
5. Medical history of sarcoidosis.
6. Oncology.
7. Exacerbation or decompensation of chronic diseases affecting ability to participate in the clinical study.
8. Medical history of polyvalent allergy.
9. Allergy/intolerance to any of the components of medications used in the treatment.
10. Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
11. Intake of medicines listed in the section "Prohibited concomitant therapy" within 1 month prior to the inclusion in the study.
12. Drug addiction, alcohol consumption at more than 2 alcohol units per day by the subject's parents/adoptive parents.
13. Mental diseases of the subject, parents/adoptive parents.
14. 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.
15. Participation in other clinical studies within 3 months prior to the inclusion in the study.
16. 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.
17. 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.

Primary outcomes:
measure: Average Illness Duration
timeFrame: From the time of randomization until the time of recovery/improvement (days 1-14)
Secondary outcomes:
measure: Percentage of Patients With Recovery/Improvement in Health
timeFrame: on days 2, 3, 4 and 5 of the treatment
measure: Changes in Body Temperature
timeFrame: baseline and days 2, 3, 4 and 5 of observation treatment
measure: Percentage of Patients With Normal Body Temperature (≤37.0ºС)
timeFrame: on days 2, 3, 4 and 5 of observation treatment
measure: Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score.
timeFrame: on days 2-6 of observation treatment
measure: Assessment of the Severity of Influenza Virus / Acute Respiratory Viral Infection Using the "Area Under the Curve" for an Overall Symptom Assessment
timeFrame: 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)
measure: Number of Intakes of Antipyretics
timeFrame: on days 1-5 of therapy
measure: Change in Viral Load During the Treatment and Follow-up Periods
timeFrame: on days 1, 3, 5, 7 of observation treatment
measure: Percentage of Patients With Exacerbation of the Disease Course
timeFrame: 14 days of observation treatment
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: City Child Health Clinical Polyclinic №13
city: Minsk
country: Belarus
facility: Municipal Health Care Institution "City Child Health Clinical Polyclinic №10"
city: Minsk
country: Belarus
facility: City Child Health Clinical Polyclinic №17
city: Moscow
country: Russian Federation
facility: Clinic of State Budgetary Institution "Research Institute of nutrition" of the Russian Academy of Medical Sciences
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University named after N.I. Pirogov
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University
city: Moscow
country: Russian Federation
facility: Russian National Research Pirogov Medical University
city: Moscow
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Moscow State Medical Academy named after I.M. Sechenov"
city: Moscow
country: Russian Federation
facility: State Budgetary Institution of Health, "Children's City Hospital № 9 named after G.N. Speranskii"
city: Moscow
country: Russian Federation
facility: State Budgetary Educational Institution of Additional Professional Education "Russian Russian Medical Academy of Postgraduate Education" of Ministry of Health of Russian Federation
city: Nizhnij Novgorod
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education " Nizhny Novgorod State Medical Academy" of Ministry of Health of Russian Federation
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education ''Novosibirsk State Medical University'' of Ministry of Health of Russian Federation
city: Perm
country: Russian Federation
facility: Municipal Health Care Institution "City Child Health Clinical Polyclinic №5"
city: Rostov-na-Donu
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "Rostov State Medical University"
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Health Care Institution "Сity Polyclinic №44"
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State health institution " City Child Health Polyclinic № 45"
city: St. Petersburg
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "St. Petersburg State Pediatric Medical Academy" of Ministry of Health of Russian Federation
city: St. Petersburg
country: Russian Federation
facility: Co.Ltd "Clinic Allergomed"
city: St. Petersburg
country: Russian Federation
facility: State Health Care Institution "Child Health City Hospital №22"
city: St.Petersburg
country: Russian Federation
facility: Limited Liability Company "Alliance Biomedical-Russian group"
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University of Ministry of Health of Russian Federation
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education " Yaroslavl State Medical Academy" of Ministry of Health of Russian Federation
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "Yaroslavl State Medical Academy"
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "Yaroslavl State Medical Academy
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl State Medical Academy
city: Vinnytsya
country: Ukraine
facility: Vinnytsya M.I. Pyrogov National Medical University
city: Zaporozh'ye
country: Ukraine
facility: Public institution "Zaporizhzhya city multidisciplinary children's hospital №5"
Study officials:
affiliation: Materia Medica Holding
name: Elena Andrianova, Professor
role: STUDY_DIRECTOR
References: