Clinical Trial of the Efficacy and Safety of Raphamin in the Treatment of Acute Bronchitis 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 Bronchitis in Adult Patients

Overview

The goal of this clinical trial is to learn if Raphamin works to treat acute bronchitis in adults. It will also learn about the efficacy and the safety of Raphamin. The main questions it aims to answer are: Will treatment with Rafamine contribute to a faster resolution of acute bronchitis symptoms, reduce the severity of the disease, and prevent the development of complications requiring antibacterial therapy compared to placebo therapy? Investigators will compare Raphamin to a placebo (a look-alike substance that contains no drug) to see if Raphamin works to treat acute bronchitis. Participants will: Take Raphamin or a placebo for 5 days. On the first day of treatment 8 tablets of Raphamin or a placebo 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. Face-to-face visits are planned in the trial: Visit 1 (Day 1), Visit 2 (Day 4±1), Visit 3 (Day 7±1), and a phone Visit 4 (day 14±1). The study uses an electronic patient diary (EPD) in which symptoms of acute bronchitis (cough, sputum, chest pain during coughing) are assessed daily.

Detailed description

The design is a multi-center, double-blind, placebo-controlled, randomized parallel-group clinical trial.

The trial will include outpatients of both sexes aged 18 to 64 years with clinical manifestations of acute bronchitis (AB) with a duration of symptoms (productive cough + one or more symptoms: dry wheezing in the lungs, "discomfort" in the chest, shortness of breath, fever) of less than 72 hours. Patients will be enrolled during the period of seasonal incidence of acute respiratory viral infections (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, pulse oximetry, objective examination, laboratory tests (complete blood count and blood biochemistry, quantification of C-reactive protein ) will be performed. Associated diseases and concomitant therapy are recorded. Before the start of therapy, a nasopharyngeal swab is taken for subsequent PCR test and verification of respiratory viruses.

If there are indications (detecting an increased heart rate of more than 100 bpm, tachypnea with a rate of more than 24 breaths per minute, or body temperature \>38˚C, or auscultation of moist rales on the affected side during examination of the patient), a posteroanterior and lateral X-ray examination of the chest organs or CT of the chest organs are performed to exclude pneumonia. It is allowed to use data from X-Ray/CT examination of the patient obtained no later than 72 hours before their inclusion in the trial.

Based on complaints, physical and instrumental examination, chronic pathology of the bronchopulmonary system and acute infectious process with lesion of the pulmonary tissue are excluded. In the presence of characteristic clinical symptoms of acute lesion of the bronchial tree and data obtained during examination, this allows a diagnosis of acute bronchitis to be made. Prior to the start of therapy, a nasopharyngeal swab is taken for subsequent PCR test and verification of respiratory viruses.

The severity of AB symptoms is assessed using the Bronchitis Severity Scale (BSS), Appendix 1.

If a patient meets the inclusion criteria are does not meet the exclusion criteria at Visit 1 (Day 1), they will be randomized to one of two groups: patients in Group 1 will receive Raphamin according to the regimen for 5 days; patients in Group 2 will receive Placebo according to the Raphamin administration regimen for 5 days.

The trial uses an electronic patient diary (EPD) where the symptoms of acute bronchitis (cough, sputum, chest pain during coughing) are assessed daily, and the Integrative Medicine Outcome Scale (IMOS), Appendix 4 is completed. Additionally, any possible deterioration in the patient's clinical condition is recorded in the diary (if applicable, for safety assessment / recording of adverse events). The investigator provides instructions to the patient on completing the diary at Visit 1.

Face-to-face visits are planned in the trial: Visit 1 (Day 1), Visit 2 (Day 4±1), Visit 3 (Day 7±1), and a phone Visit 4 (day 14±1). Patients visit the physician, or the physician visits patients, at a medical center or at home. In case of deterioration in the patient's condition or at the physician's decision, an unscheduled visit may be conducted throughout the trial.

During Visits 1-3, the physician performs a physical examination, records vital signs (RR, HR, BP, body temperature), performs pulse oximetry, records the dynamics of disease symptoms (according to the BSS), completes the European Quality of Life Instrument (EQ-5D) (Appendix 3), records the administration of basic and concomitant medications. At Visits 2 and 3, the physician monitors the completion of the EPD. At Visit 3, compliance is assessed. At Visit 4 (telephone visit), the physician assesses safety, collects information about the patient's condition, the presence/absence of complications, the use of antibacterial drugs, and the presence/absence of patient's hospitalization.

During the trial, patients may receive baseline therapy as indicated: a mucolytic for tight productive cough (Lazolvan® MAX, 1 capsule of 75 mg once daily for tight productive cough), analgesics and antipyretics for hyperthermia above 38°C (ibuprofen and/or paracetamol), therapy for concomitant diseases, excluding medications specified in the "Prohibited concomitant therapy" section.

Interventions

• Drug Raphamin
  Oral administration
• Drug Placebo
  Oral administration

Primary outcome measures

• Proportion of patients with the Bronchitis Severity Scale, (BSS) score of 4 points or less [Time frame: On day 4]

Secondary outcome measures (12)

• Change in the total Bronchitis Severity Scale, (BSS) score [Time frame: 7 days]
• Proportion of patients with the BSS score of 4 points or less [Time frame: On day 7]
• Proportion of patients with a decrease in the BSS score by 5 points or more [Time frame: On 4 and 7 days]
• Change in the severity of acute bronchitis symptoms (cough, sputum, and chest pain) [Time frame: 14 days]
• Proportion of patients with no individual symptoms (cough, sputum, wheezing, chest pain during cough, shortness of breath) according to the BSS [Time frame: On 4 and 7 days]
• Time to effect of therapy according to the IMOS [Time frame: 14 days]
• European Quality of Life Instrument (EQ-5D) total score [Time frame: On 4 and 7 days]
• Proportion of patients with worsening of bronchitis requiring systemic antibacterial therapy [Time frame: 14 days]
• Proportion of patients hospitalized due to worsening of acute bronchitis [Time frame: 14 days]
• Number of participants with AEs [Time frame: 14 days]
• The intensity (severity) ofAEs [Time frame: 14 days]
• Causal relationship of AEs to the sudy drug [Time frame: 14 days]

Eligibility criteria

Inclusion criteria

• Male and female patients aged 18 to 64 years, inclusive.
• Confirmed diagnosis of acute bronchitis (AB) based on the presence of productive cough and one or more symptoms (wheezing in the lungs, chest "discomfort", shortness of breath, fever).
• The BSS score of at least 5 and no more than 15 points.
• Duration of AB symptoms does no more than 72 hours.
• Seasonal incidence of acute respiratory viral infections.
• Availability of a patient information sheet and an informed consent form for participation in the clinical trial signed by the patient.
• Patients who have agreed to use a reliable method of contraception during the study (for men and women of reproductive potential).

Exclusion criteria

• History of chronic obstructive pulmonary disease, chronic bronchitis, asthma, bronchiectasis, or pulmonary emphysema.
• Suspected pneumonia or bacterial infection (including otitis media, sinusitis, urinary tract infection, meningitis, sepsis, etc.) requiring antibiotics, starting on the first day of illness.
• Suspected infiltrative pulmonary tuberculosis, pulmonary embolism, pulmonary infarction, drug-induced (toxic) pneumopathy, foreign body aspiration, sarcoidosis, pulmonary alveolar proteinosis, lipoid pneumonia, or atelectasis.
• History of immunopathological diseases: systemic vasculitis, lupus pneumonitis, allergic bronchopulmonary aspergillosis, obliterating bronchiolitis, idiopathic pulmonary fibrosis, eosinophilic pneumonia, bronchocentric granulomatosis.
• Chronic heart failure with functional classes III and IV (according to the classification of the New York Heart Association, 1964).
• Metabolic disorders (obesity grades 2-3).
• History of chronic kidney disease (classes C3-5 A3); liver failure (class C according to Child-Pugh); neurological conditions (neuromuscular, neurocognitive disorders, epilepsy); hemoglobinopathy.
• Primary and/or secondary immunodeficiency (HIV infection, administration of immunosuppressive drugs, etc.).
• Surgery of any localization within the last 3 months.
• Clinical symptoms of severe influenza/ARI requiring hospitalization .
• Acute respiratory failure.
• History/suspected oncological disease of any location (except for benign neoplasms).
• Exacerbation or decompensation of chronic diseases that affect the patient's ability to participate in the clinical trial, including diabetes mellitus.
• Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia.
• Pregnancy, breastfeeding, and childbirth less than 3 months prior to study inclusion.
• Hypersensitivity to any component of the medications used in the treatment.
• Patients who have taken medications listed in the "Prohibited Concomitant Medication" section in the previous 1 month prior to study inclusion or who require medications prohibited for use in this study.
• Patients who, in the investigator's opinion, will not comply with study monitoring requirements or with the study drugs administration schedule.
• History of mental illness, alcoholism, or drug abuse that, in the investigator's opinion, will interfere with successful compliance with study procedures.
• Participation in other clinical trials within 3 months prior to study inclusion.
• The patient is a member of the center's research staff directly involved in the study and is an immediate family member of the investigator. Immediate family members are defined as spouses, parents, children, or siblings, regardless of whether they are biological or adopted.
• The patient is employed by NPF MATERIA MEDICA HOLDING LLC, i.e., is an employee of the company, a temporary contract worker, or a designated official responsible for the study, or is an immediate family member of one of these individuals..

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 · 33 centers

• Aramil City Hospital — Aramil
• Gatchina Clinical Interdistrict Hospital — Gatchina
• City Clinical Hospital No # 9 of the Ministry of Health of the Udmurt Republic — Izhevsk
• Kazan State Medical University/Department of Infectious Diseases — Kazan'
• Kazan State Medical University/Department of Internal Medicine — Kazan'
• Main Military Clinical Hospital named after Academician N.N. Burdenko/Therapeutic departme — Moscow
• First Moscow State Medical University named after I.M. Sechenov/University Clinical Hospit — Moscow
• LLC "Persona Group of Companies" — Nizhny Novgorod
• … and 25 more centers

Identifiers

NCT: NCT07650227 · MMH-407-012

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗