Clinical trial NCT04918771: Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old
Official title: Multicenter Double Blind Placebo-controlled Parallel-group Randomized Clinical Study of Efficacy and Safety of Raphamin in the Treatment of Acute Respiratory Viral Infection in Children Aged 12-18 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Respiratory Viral Infection
Lead sponsor: Materia Medica Holding
Sponsor class: INDUSTRY
First posted: 2021-06-09
Enrollment: 435
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The multicenter double-blind placebo-controlled randomized in parallel-group. The objective of this study is to evaluate efficacy and safety of Raphamin in the treatment of acute respiratory viral infection (ARVI) in children aged 12-18 years old.

Detailed description: Design: a multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial.

The study will enroll outpatient subjects of either gender aged 12-18 old years with clinical manifestations of acute respiratory viral infection (ARVI) within the first days after the onset of the disease. The patients will be recruited during seasonal ARVI morbidity. Collection of history, thermometry, objective examination, laboratory tests, recording concomitant therapy will be made after parent/adoptive parent signing information sheet and informed consent form for the child participation in the clinical study, for children ≥14 years old after signing patient information sheet and informed consent form for children ≥14 years old to participate in the clinical study. The severity of ARVI symptoms will be evaluated with a 4-point scale.

The nasopharyngeal swabs for PCR diagnosis and verification of respiratory viruses will be performed prior to therapy to confirm the viral etiology of ARVI. To rule out the infection caused by the new coronavirus COVID-19 (Coronavirus disease 2019), a rapid test for SARS-CoV-2 antigen will be made. In case of a positive SARS-CoV-2 test, the physician will act in accordance with the current version of the RF MoH Temporary methodological recommendations "Prevention, diagnosis, and therapy of new coronavirus infection (COVID-19)".

If a patient meets all inclusion criteria and does not have any exclusion criteria, at Visit 1 (Day 1), he/she will be randomized into one of two groups: patients of group 1 will take Raphamin according to the dosage regimen for 5 days; patients of group 2 will take Placebo using Raphamin 5-day regimen.

The study will use an electronic patient diary (EPD) for recording morning and evening axillary body temperature (using a classic mercury-free thermometer) and disease symptoms (Symptom Severity Score). Besides, antipyretic dosing (if applicable) and any deterioration in a patient's condition (if applicable, for safety evaluation/AE documentation) will also be recorded in a patient diary. The investigator will provide instructions on filling the diary. At Visit 1 the parent/adoptive parent together with an investigator will record ARVI symptom severity and body temperature in the diary.

Patients will be observed for 14 days (screening, randomization - up to 1 day, treatment period - 5 days, follow-up - up to 2 days; deferred "phone visit" - day 14).

During the treatment and follow-up period the patients/physicians will make 3 visits and the fourth "phone visit" will be scheduled additionally: 1) visits by physician/patient - on Days 1, 5, and 7 (Visits 1, 2, and 3) - in a study center or at home; 2) "phone visit" (Visit 4) - on Day 14.

At Visits 2 and 3, the investigator will perform an objective examination, document changes in the symptoms and concomitant medications, and check patient diaries. At Visit 3 laboratory tests will be performed and compliance will be checked.

"Phone visit" will be performed to interview parents/adoptive parents about the patient's condition, presence/absence of secondary bacterial/viral complications, and use of antibiotics.

During the study, symptomatic therapy and therapy for their co-morbidities are allowed with the exception of the drugs indicated in the section "Prohibited Concomitant Treatment".

Eligibility criteria: Inclusion Criteria:

1. Patients of either gender aged 12 to 18 years.
2. Diagnosis of ARVI based on medical examination: axillary temperature ≥ 37.8°C at examination + non-specific flu-like symptoms score ≥4, nasal/throat/chest symptom score ≥2.
3. The first 24 hours after ARVI onset.
4. Contraceptive measures by sexually active adolescents of both genders during the study.
5. Patient information sheet (informed consent form) signed by one parent/adoptive parent of the patient and there is also a signed patient information sheet (informed consent form) for children aged 14 and over.

Exclusion Criteria:

1. Clinical symptoms of severe influenza/ARVI requiring hospitalization.
2. Positive SARS-CoV-2 (COVID-19/Coronavirusdisease2019) antigen test.
3. Suspected pneumonia, bacterial infection (including otitis media, sinusitis, urinary tract infection, meningitis, sepsis, etc.) requiring administration of antibiotics from the first day of illness.
4. Suspected initial manifestations of diseases with symptoms similar to ARVI at onset (other infectious diseases, flu-like syndrome at the onset of systemic connective tissue diseases, and other pathology).
5. Patients requiring antiviral medication prohibited within the study.
6. Medical history of primary and secondary immunodeficiency.
7. Medical history/suspicion of oncology of any localization (except for benign neoplasms).
8. Aggravation or decompensation of chronic diseases (diabetes mellitus, infantile cerebral paralysis, cystic fibrosis, primary ciliary dyskinesia, bronchopulmonary dysplasia, respiratory and ENT congenital defects, etc.) affecting a patient's ability to participate in the clinical trial.
9. Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
10. Allergy/ hypersensitivity to any component of the study drugs used in the treatment.
11. Pregnancy. Breast-feeding.
12. Use of medications specified in the section "Prohibited Concomitant Therapy" within two weeks prior to inclusion in the study.
13. Patients whose parents/adopters, from the investigator's point of view, will not comply with the observation requirements during the study or follow the procedure for taking the study drugs.
14. Medical history of mental diseases of the patient or their parent(s)/adoptive parents.
15. Participation in other clinical trials for 3 months prior to enrollment in this study.
16. Patient's parents/adopters who are related to any of the on-site research personnel directly involved in the study or are an immediate relative of the investigator. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted).
17. The patient's parent/adopter who work for OOO "NPF "MATERIA MEDICA HOLDING" (i.e. the company's employees, temporary contract workers, designated officials responsible for carrying out the research or any immediate relatives of the aforementioned).

Primary outcomes:
measure: Time to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms (ARVI, Confirmed by Polymerase Chain Reaction (PCR)).
timeFrame: 14 days of observation
Secondary outcomes:
measure: Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed).
timeFrame: Day1 through Day6 of the treatment and observation
measure: Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed).
timeFrame: 14 days of observation
measure: Time to Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed).
timeFrame: 14 days of observation
measure: Percentage of Patients With Resolution of ARVI Symptoms (PCR-confirmed).
timeFrame: 14 days of observation
measure: Dosing Frequency of Antipyretics.
timeFrame: 3 days of therapy
measure: Percentage of Patients Reporting Worsening of Illness.
timeFrame: Day 4 through day 14 of the treatment and observation period
measure: Occurrence and Type of Adverse Events (AE) During the Treatment. AE Severity.
timeFrame: 14 days of observation
measure: Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm).
timeFrame: Day 1 through day 7 of the treatment and observation period.
measure: Changes in Vital Signs: Respiration Rate/Breathing Rate in Breaths Per Minute.
timeFrame: Day 1 through day 7 of the treatment and observation period.
measure: Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg).
timeFrame: Day 1 through day 7 of the treatment and observation period.
measure: Percentage of Patients With Clinically Relevant Abnormal Laboratory Findings.
timeFrame: Day 1 through day 7 of the treatment and observation period.
Other outcomes:
Locations:
city: Ekaterinburg
country: Russian Federation
facility: LLC "European Medical Center "UMMC-Health"
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Kazan
country: Russian Federation
facility: Llc "Medlight"
city: Krasnodar
country: Russian Federation
facility: Specialized Clinical Hospital for Infectious Diseases
city: Moscow
country: Russian Federation
facility: Llc "Olla-Med"
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University named after N.I. Pirogov
city: Moscow
country: Russian Federation
facility: Morozovskaya Children's City Clinical Hospital of the Moscow Department of Health
city: Moscow
country: Russian Federation
facility: Federal Scientific and Clinical Center for Physical and Chemical Medicine of the Federal Medical and Biological Agency
city: Moscow
country: Russian Federation
facility: Llc "Diagnostics and Vaccines"
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Medical University
city: Perm
country: Russian Federation
facility: City Children's Clinical Polyclinic # 5
city: Perm
country: Russian Federation
facility: LLC "Professorial Clinic"
city: Rostov-on-Don
country: Russian Federation
facility: Clinical and diagnostic center "Health" of the city of Rostov-on-Don
city: Rostov-on-Don
country: Russian Federation
facility: Children's City Hospital #1 of Rostov-on-Don city
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University named after academician I.P. Pavlov
city: Saint Petersburg
country: Russian Federation
facility: Children's city polyclinic # 44
city: Saint Petersburg
country: Russian Federation
facility: LLC "Energy of health"
city: Saint Petersburg
country: Russian Federation
facility: Children's city polyclinic # 35
city: Saint Petersburg
country: Russian Federation
facility: Research Institute of Influenza named after A.A. Smorodintsev
city: Samara
country: Russian Federation
facility: Samara Regional Children's Clinical Hospital named after N.N. Ivanova
city: Saransk
country: Russian Federation
facility: National Research Mordovian State University named after N.P. Ogarev
city: Saratov
country: Russian Federation
facility: LLC "DNA Research Center"
city: Smolensk
country: Russian Federation
facility: Smolensk State Medical University
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University/Department of Outpatient and Emergency Pediatrics
city: Volgograd
country: Russian Federation
facility: Volgograd State Medical University/Department of Pediatrics and Neonatology
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl State Medical University/Department of Pediatrics IPGE
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl State Medical University/Department of Pediatrics № 2
city: Yaroslavl
country: Russian Federation
facility: Clinical Hospital # 2
Study officials:
References: