The Efficacy and Safety of Raphamin in the Treatment of Acute Rhinosinusitis in Adult Patients

Official title

Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-group Clinical Trial of the Efficacy and Safety of Raphamin in the Treatment of Acute Rhinosinusitis in Adult Patients

Overview

Multicenter double-blind placebo-controlled randomized in parallel groups clinical trial of the efficacy and safety of Raphamin in the treatment of acute rhinosinusitis in adult patients.

Detailed description

A multicenter, double-blind, placebo-controlled, randomized, parallel-group clinical trial.

The trial will enroll outpatients of either gender aged 18 to 75 years with clinical manifestations of acute rhinosinusitis (ARS) within the first 48 hours after the disease onset. Patient recruitment will be conducted during the seasonal incidence of acute respiratory viral infection (ARVI). After the patient signs the information sheet and informed consent form for participation in the clinical trial, the medical history will be collected, thermometry, objective examination, laboratory tests will be performed, concomitant diseases and concomitant therapy will be recorded. The severity of ARS symptoms will be assessed using Major Symptom Score (MSS). Initially (Day 1) and on Visits 2 (Day 4) and 3 (Day 7), the patient together with the investigator, fills in the MSS scale and completes the Sino-Nasal Outcome Test questionnaire for assessing the quality of life of patients with diseases of the nose and paranasal sinuses (SNOT-22).

If all inclusion criteria are met and there no any exclusion criteria, at Visit 1 (Day 1), the patient is 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 uses an electronic patient diary (EPD) where the patient daily morning and evening will make records axillary body temperature (measured with a classic mercury-free thermometer) and symptoms of the disease (according to the MSS). In addition, administration of basic therapy drugs (if applicable) as well as any possible worsening of the patient's condition (if applicable, to assess safety / to record adverse events) should also be recorded in the patient diary. The investigator will instruct the patient on how to complete the diary. At Visit 1, the patient will record the severity of ARS symptoms and body temperature in the diary together with the physician.

The patient will be observed for 14 days (screening, randomization - up to 1 day, treatment - 5 days, follow-up - up to 14 days).

During the treatment and follow-up period, patients/physicians will pay 3 visits, on days 1, 4 and 7 (Visits 1, 2 and 3) - at a medical center or at home; a phone visit (Visit 4) will be on day 14.

At Visits 2 and 3, the investigator performs objective examination, records changes in the disease symptoms, concomitant therapy, and controls the filling of the diary, evaluates the patient's compliance (Visit 3). At Visit 4 (a phone visit), the investigator evaluates safety, collects information about the patient's condition, the presence/absence of complications, the use of antibiotics, and the presence/absence of hospitalization of the patient.

Symptomatic therapy and therapy for concomitant diseases will be permitted during the trial except for the drugs listed under "Prohibited Concomitant Treatment".

Interventions

• Drug Raphamin
  Oral administration
• Drug Placebo
  Oral administration

Primary outcome measures

• Percentage of patients with improvement of acute rhinosinusitis symptoms on day 4 [Time frame: On 4 day]

Secondary outcome measures (12)

• Percentage of patients with improvement of acute rhinosinusitis symptoms on day 7 [Time frame: On 7 day of observation]
• Change in SNOT-22 total score [Time frame: On days 1, 4 and 7]
• Change in MSS total score [Time frame: From day 1 to day 14]
• Change in the SNOT-22 nasal domain score [Time frame: On days 1, 4 and 7]
• Percentage of patients with worsening of rhinosinusitis requiring systemic/topical antibiotics [Time frame: On 14 day]
• Proportion of patients hospitalized due to worsening rhinosinusitis [Time frame: On 14 day]
• Percentage of patients with prolonged rhinosinusitis [Time frame: On 14 day]
• Number of Participants With Adverse Events (AEs) [Time frame: From day 1 to day 14]
• Severity of AEs [Time frame: From day 1 to day 6]
• Causal Relationship of AEs to the Sudy Drug [Time frame: From day 1 to day 6]
• Outcome of AEs [Time frame: From day 1 to day 6]
• Changes in Vital Signs (Blood Pressure) [Time frame: On days 1, 4 and 7]

Eligibility criteria

Inclusion criteria

• Male and female aged 18 - 75 years.
• Diagnosis of acute rhinosinusitis:

• 8-12 points on MSS scale;
• no more than 3 severe symptoms (3 points on the MSS scale)
• facial pain/heaviness in the facial area 1-2 points on the MSS scale.
• Disease duration up to 48 hours (from the onset of the first symptoms of the disease).
• Availability of a patient information sheet and an informed consent form for participation in the clinical trial signed by the patient.
• Patients who agreed to use a reliable method of contraception during the study (for men and women of reproductive potential).

Exclusion criteria

• Symptoms of acute bacterial rhinosinusitis (three or more of those below):

• fever of ≥ 38.0°C;
• the second wave of ARS symptoms;
• one-sided process;
• facial pain/pressure of 3 points (on the MSS scale).
• Recurrent ARS (≥4 episodes of ARS per year with complete resolution of symptoms between episodes).
• Odontogenic rhinosinusitis.
• Allergic (seasonal or year-round) rhinitis.
• Nasal polyps or clinically significant nasal septum deviation.
• Concomitant otitis.
• Use of intranasal or systemic corticosteroids for 30 days prior to the screening visit.
• Use of intranasal or systemic antibiotics for 30 days prior to the screening visit.
• Surgery for the nasal cavity and paranasal sinuses during the last 6 months before the screening visit.
• Any other surgery during the last 3 months.
• Clinical symptoms of severe influenza/ARVI requiring hospitalization.
• Suspected bacterial infection of any localization requiring the administration of antibiotics from the first day of disease.
• History/suspicion of oncology of any localization (except for benign neoplasms).
• Exacerbation or decompensation of chronic diseases (diabetes mellitus, bronchial asthma, chronic bronchitis, chronic obstructive pulmonary disease, 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.
• Previously diagnosed immunodeficiency of any etiology.
• Unstable angina or myocardial infarction during the last 6 months.
• Class III and IV chronic heart failure (according to the classification of the New York Heart Association, 1964).
• History of chronic kidney disease (classes C3-5 A3).
• History of liver failure (class C according to Child-Pugh).
• Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
• Pregnancy, breast-feeding, and childbirth less than 3 months before inclusion in the trial.
• Hypersensitivity to any component of the medicines used in the treatment.
• Patients who used medications listed under "Prohibited Concomitant Treatment" within 1 month prior to inclusion in the trial or need medications prohibited for use in the trial.
• Patients who, from the investigator's point of view, will not comply with the observation requirements during the trial or follow the procedure for taking the test drugs.
• History of mental illness, alcoholism, drug abuse, which, from the investigator's point of view, will prevent the patient from following the trial procedures.
• Participation in other clinical trials within 3 months prior to inclusion in this trial.
• Patient is related to on-site research personnel directly involved in the trial, or is the immediate family member of the investigator. 'Immediate family members' mean spouses, parents, children, or siblings, whether related or adopted.
• Patient is employed by OOO "NPF "MATERIA MEDICA HOLDING", i.e., is an employee of the company, a temporary contract employee, or a designated official responsible for conducting the trial or their immediate family member.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Russia · 44 centers

• Aramil city hospital — Aramil
• Gatchina Clinical Interdistrict Hospital — Gatchina
• Baltic Federal University named after Immanuel Kant — Kaliningrad
• Kazan State Medical University/Department of Infectious Diseases — Kazan'
• Kuban State Medical University/Department of Infectious Diseases and Phthisiopulmonology — Krasnodar
• City Polyclinic # 2 of the Moscow City Department of Health — Moscow
• First Moscow State Medical University named after I.M. Sechenov/Department of Ear, Nose an — Moscow
• National Medical Research Center of Otolaryngology — Moscow
• … and 36 more centers

Identifiers

NCT: NCT06901297 · MMH-407-011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗