Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old
- Registration Number
- NCT04918771
- Lead Sponsor
- Materia Medica Holding
- 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".
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 435
- Patients of either gender aged 12 to 18 years.
- 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.
- The first 24 hours after ARVI onset.
- Contraceptive measures by sexually active adolescents of both genders during the study.
- 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.
- Clinical symptoms of severe influenza/ARVI requiring hospitalization.
- Positive SARS-CoV-2 (COVID-19/Coronavirusdisease2019) antigen test.
- Suspected pneumonia, bacterial infection (including otitis media, sinusitis, urinary tract infection, meningitis, sepsis, etc.) requiring administration of antibiotics from the first day of illness.
- 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).
- Patients requiring antiviral medication prohibited within the study.
- Medical history of primary and secondary immunodeficiency.
- Medical history/suspicion of oncology of any localization (except for benign neoplasms).
- 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.
- Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
- Allergy/ hypersensitivity to any component of the study drugs used in the treatment.
- Pregnancy. Breast-feeding.
- Use of medications specified in the section "Prohibited Concomitant Therapy" within two weeks prior to inclusion in the study.
- 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.
- Medical history of mental diseases of the patient or their parent(s)/adoptive parents.
- Participation in other clinical trials for 3 months prior to enrollment in this study.
- 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).
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Raphamin Raphamin Tablet for oral use. Placebo Placebo Tablet for oral use.
- Primary Outcome Measures
Name Time Method Time to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms (ARVI, Confirmed by Polymerase Chain Reaction (PCR)). 14 days of observation 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.
- Secondary Outcome Measures
Name Time Method Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed). Day1 through Day6 of the treatment and observation 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.Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed). 14 days of observation 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 to Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed). 14 days of observation 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.
Percentage of Patients With Resolution of ARVI Symptoms (PCR-confirmed). 14 days of observation Outcome Measure is based on the Percentage of Patients With Resolution 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.Dosing Frequency of Antipyretics. 3 days of therapy Outcome Measure is based on the rates of antipyretic use per patient during days 1 to 3 of therapy according to the electronic patient diary.
Percentage of Patients Reporting Worsening of Illness. Day 4 through day 14 of the treatment and observation period Outcome Measure is based on the rates of Complications that require the use of antibiotics or hospitalization.
Occurrence and Type of Adverse Events (AE) During the Treatment. AE Severity. 14 days of observation 1. The intensity (severity) of adverse events.
2. Causal relationship of AEs to the sudy drug.
3. Outcome of AEs. Based on medical records.Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm). Day 1 through day 7 of the treatment and observation period. The outcome measure is based on the medical records. The patient's heart rate (heart rate) is measured by the physician in every visit (on days 1, 5, and 7).
Changes in Vital Signs: Respiration Rate/Breathing Rate in Breaths Per Minute. Day 1 through day 7 of the treatment and observation period. Outcome Measure is based on the medical records. The patient's respiration rate (breathing rate) is measured by physician in every visit (on days 1, 5, and 7).
Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg). Day 1 through day 7 of the treatment and observation period. Outcome Measure is based on the medical records. The patient's blood pressure is measured by the physician in every visit (on days 1, 5, and 7).
Percentage of Patients With Clinically Relevant Abnormal Laboratory Findings. Day 1 through day 7 of the treatment and observation period. Outcome Measure is based on the Hematology, blood chemistry, and urinalysis parameters, which are beyond the reference values at the end of treatment.
Trial Locations
- Locations (29)
LLC "European Medical Center "UMMC-Health"
🇷🇺Ekaterinburg, Russian Federation
Kazan State Medical University
🇷🇺Kazan, Russian Federation
Llc "Medlight"
🇷🇺Kazan, Russian Federation
Specialized Clinical Hospital for Infectious Diseases
🇷🇺Krasnodar, Russian Federation
Llc "Olla-Med"
🇷🇺Moscow, Russian Federation
Russian National Research Medical University named after N.I. Pirogov
🇷🇺Moscow, Russian Federation
Morozovskaya Children's City Clinical Hospital of the Moscow Department of Health
🇷🇺Moscow, Russian Federation
Federal Scientific and Clinical Center for Physical and Chemical Medicine of the Federal Medical and Biological Agency
🇷🇺Moscow, Russian Federation
Llc "Diagnostics and Vaccines"
🇷🇺Moscow, Russian Federation
Novosibirsk State Medical University
🇷🇺Novosibirsk, Russian Federation
Scroll for more (19 remaining)LLC "European Medical Center "UMMC-Health"🇷🇺Ekaterinburg, Russian Federation