Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old

Materia Medica Holding435 enrolled

Overview

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.

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".

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

435

Conditions

Acute Respiratory Viral Infection

Interventions

RaphaminDRUG

Oral administration - not with food. Keep the tablet in the mouth until it is completely dissolved. On the 1st day of treatment, 8 tablets are taken according to the following scheme: 1 tablet every 30 minutes in the first 2 hours (a total of 5 tablets in 2 hours), then during the same day, take another 1 tablet 3 times at regular intervals. On the 2nd day and then take 1 tablet 3 times a day. The duration of treatment is 5 days.

PlaceboDRUG

Oral administration - not with food. Placebo using Raphamin scheme.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 18 Years

Medical Language ↔ Plain English

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).

Locations (29)

Outcomes

Primary Outcomes

Time to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms (ARVI, Confirmed by Polymerase Chain Reaction (PCR)).

Outcome Measure is evaluated on the basis of ARVI, confirmed by Polymerase chain reaction (PCR), i.e virus detection. ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 7 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough, pain/heaviness in chest) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the following scale: ≤37.3 С=0 points; 37.4-38.0 С=1 point; 38.1-39.0 С=2 points; ≥39.1 С=3 points. So the range of TSS was from "0" to "42". The TSS higher score is the worse outcome.

Time frame: 14 days of observation

Secondary Outcomes

Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed).

The outcome measure is based on the area under the curve (AUC) for the TSS (Total symptoms score). TSS is calculated as a sum of scores for 14 different symptoms. 13 of them are different ARVI manifestations, each of them is evaluated on a scale: 0 (none), 1 (mild), 2 (moderate), 3 (severe). 14th symptom is body temperature (temp) which is converted to its score using following rules: if temp \<= 37.3 then score = 0 (none) if 37.3 \< temp \<= 38.0 then score = 1 (mild) if 38.0 \< temp \<= 39.0 then score = 2 (moderate) if 39.0 \< temp then score = 3 (severe) So it is 14 symptoms and the score for each of them varies between 0 and 3. Minimum TSS is 0, maximum is 42 (higher TSS score is worse). AUC is calculated for all timepoints available for patient.

Time frame: Day1 through Day6 of the treatment and observation

Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed).

ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 7 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough, pain/heaviness in chest) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the following scale: ≤37.3 С=0 points; 37.4-38.0 С=1 point; 38.1-39.0 С=2 points; ≥39.1 С=3 points. So the range of TSS was from "0" to "42". The TSS higher score is the worse outcome.

Data from ClinicalTrials.gov

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