A Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-group Clinical Trial of the Efficacy and Safety of Raphamin in the Treatment of Acute Respiratory Viral Infection in Children Aged 3-12 Years
Overview
- Phase
- Phase 3
- Intervention
- Raphamin
- Conditions
- Acute Respiratory Viral Infection
- Sponsor
- Materia Medica Holding
- Enrollment
- 374
- Locations
- 63
- Primary Endpoint
- Time to resolution of ARVI symptoms (PCR-confirmed)
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
Multicenter double-blind placebo-controlled randomized in parallel groups clinical trial.
Detailed Description
Design: a multicenter, double-blind, placebo-controlled, randomized, parallel-group clinical trial. The trial will enroll outpatients of either gender aged 3 to 12 years with clinical manifestations of acute respiratory viral infection (ARVI) within the first 24 hours after the disease onset. Patient enrollment will be conducted in 2 stages during the seasonal incidence of ARVI. First, children aged 6-12 years will be enrolled in the trial. Once the required number of patients is reached, an "unblinded" interim analysis with the primary efficacy endpoint assessment and safety analysis will be performed. Based on the data from the unblinded interim analysis, a decision will be made whether the age range of enrollment can be expanded from 3 to 12 years. Patient enrollment will not be stopped until the results of the "unblinded" interim analysis are available. After the parent/adopter signs the information sheet and informed consent form for the patient's parents/adopters to participate in the clinical trial, the medical history will be collected, thermometry, objective examination, laboratory tests will be performed, and concomitant therapy will be recorded. The severity of ARVI symptoms will be assessed using 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. If a patient meets all inclusion criteria and does not have any exclusion criteria, at Visit 1 (Day 1), they will be randomized into one of two groups: Group 1 patients will receive Raphamin according to the dosage regimen for 5 days; Group 2 patients will receive Placebo using the Raphamin dosage regimen for 5 days. The trial will utilize an electronic patient diary (EPD) where the patient will make daily records of morning and evening axillary body temperature (measured with a classic mercury-free thermometer) and symptoms of the disease (ARVI Symptom Severity Score). In addition, antipyretic dosing (if applicable) as well as any possible worsening of the patient's condition (if applicable, to assess safety / to record adverse events) will also be recorded in the patient diary. The investigator will instruct the parent/adopter on how to complete the diary. At Visit 1, the parent/adopter together with the physician will record the severity of ARVI symptoms and body temperature in the diary. The patient will be observed for 14 days (screening, randomization - up to 1 day, treatment - 5 days, follow-up - up to 2 days; deferred "phone visit" - day 14). During the treatment and follow-up period, patients/physicians will pay 3 visits, and the fourth "phone visit" will be scheduled additionally: 1) physician/patient visits - on days 1, 5 and 7 (Visits 1, 2 and 3) - at the health center or at home; 2) a phone "visit" by the physician (Visit 4) - on day 14. During Visits 2 and 3, the physician will perform objective examination, record changes in the disease symptoms, concomitant therapy, and monitor the completion of the diary. During Visit 3, compliance will be assessed and laboratory tests will be performed. A phone "visit" will be performed to interview the parent/adopter about the patient's condition, presence/absence of secondary bacterial/viral complications, and use of antibiotics. Symptomatic therapy and therapy for concomitant diseases will be permitted during the trial except for the drugs listed under "Prohibited Concomitant Treatment".
Investigators
Eligibility Criteria
Inclusion Criteria
- •Children of either gender aged 3 to12 years .
- •Diagnosis of ARVI based on the medical examination: axillary temperature ≥37.8°C at the time of examination + total severity of general symptom score ≥4 points, nasal/throat/chest symptoms ≥2 points (ARVI Symptom Severity Score).
- •24 hours from the ARVI onset .
- •Availability of a patient information sheet and an informed consent form for the patient's parents/adopters for patient participation in the clinical trial signed by one parent/adopter of the patient.
Exclusion Criteria
- •Clinical symptoms of severe influenza/ARVI requiring hospitalization.
- •Suspected pneumonia, bacterial infection (including otitis media, sinusitis, urinary tract infection, meningitis, sepsis, etc.) requiring the administration of antibiotics from the first day of disease.
- •Suspected early manifestations of diseases that have onset symptoms similar to those of ARVI (other infectious diseases, influenza-like syndrome at the onset of systemic connective tissue diseases and other pathologies).
- •Patients who require administration of antiviral medications that are prohibited for use in this trial.
- •History or prior diagnosis of primary and secondary immunodeficiency.
- •History/suspicion of oncology of any localization (except for benign neoplasms).
- •Exacerbation or decompensation of chronic diseases (diabetes mellitus, cerebral palsy, cystic fibrosis, primary ciliary dyskinesia, bronchopulmonary dysplasia, malformations of the respiratory and ENT organs, etc.) affecting the patient's ability to participate in the clinical trial.
- •Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
- •Allergy/hypersensitivity to any component of the medicines used in the treatment.
- •Use of medications listed under "Prohibited Concomitant Treatment" within 2 weeks prior to inclusion in the trial.
Arms & Interventions
Raphamin
Per os without food. The tablet should be kept in mouth until completely dissolved. On day 1 of treatment, 8 tablets should be taken using the following regimen: 1 tablet every 30 minutes for the first 2 hours (5 tablets in total for 2 hours), then 1 more tablet 3 times at equal intervals during the same day. On day 2 and onwards, 1 tablet should be taken 3 times a day. The duration of treatment is 5 days.
Intervention: Raphamin
Placebo
Placebo using the Raphamin dosage regimen.
Intervention: Placebo
Outcomes
Primary Outcomes
Time to resolution of ARVI symptoms (PCR-confirmed)
Time Frame: 14 days
Time from recording the disease symptoms at Visit 1 until resolution of the disease symptoms. Resolution of ARVI symptoms will be defined if axillary temperature is ≤37.3°C for 24 hours (without further increase during observation period) + lack/presence of ARVI general symptoms ≤2 points. Based on the patient's diary.
Secondary Outcomes
- Percentage of patients with resolution of ARVI symptoms (PCR-confirmed)(14 days)
- Dosing frequency of antipyretics(From day 1 to day 3)
- Percentage of patients with worsening of the disease(From day 4 to day 14)
- Number of Participants With Adverse Events (AEs)(From day 1 to day 6)
- Severity of AEs(From day 1 to day 6)
- Causal Relationship of AEs to the Sudy Drug(From day 1 to day 6)
- Outcome of AEs(From day 1 to day 6)
- Changes in Vital Signs (Blood Pressure) measured in mm Hg(On Visit 1 (day 1), Visit 2 (day 5) and Visit 3 (day 7))
- Changes in Vital Signs (Heart Rate)(On Visit 1 (day 1), Visit 2 (day 5) and Visit 3 (day 7))
- Changes in Vital Signs (Breathing Rate)(On Visit 1 (day 1), Visit 2 (day 5) and Visit 3 (day 7))
- Changes in Vital Signs (Axillary temperature)(On Visit 1 (day 1), Visit 2 (day 5) and Visit 3 (day 7))
- Percentage of Patients With Clinically Significant Abnormal Laboratory Tests(On Visit 1 (day 1) and Visit 2 (day 5))
- ARVI severity (clinically diagnosed, including PCR-confirmed)(From day 1 to day 6)
- Percentage of patients with resolution of ARVI symptoms(14 days)
- Time to resolution of ARVI symptoms(14 days)