Efficacy and Safety of Rengalin in the Treatment of ARVI Cough in Children

Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-group Clinical Trial of the Efficacy and Safety of Rengalin in the Treatment of Cough in Acute Viral Upper Respiratory Tract Infections Tract Infections in Children During the Epidemic Growth of Influenza and ARVI

The goal of this clinical trial is to evaluate the efficacy and safety of liquid dosage form of Rengalin in the treatment of cough in acute viral upper respiratory tract infections infections in children in during the epidemic growth of influenza and ARVI. The main questions it aims to answer are:

Investigators will compare the liquid dosage form of Rengalin to a placebo (a look-alike substance that contains no drug) to see if Rengalin in the liquid dosage form works for cough in acute viral upper respiratory tract infections in children.

Participants will:

Take the liquid dosage form of Rengalin or placebo per os 5 ml per administration 3 times a day for 7 days.

The design is a multicenter, double-blind, placebo-controlled, randomized, parallel-group clinical trial evaluating the efficacy and safety of the study therapy.

The trial will enroll children of either gender aged 6 months to 3 years, who consulted a physician for dry/non-productive cough caused by acute viral upper respiratory tract infections during the seasonal growth of influenza and ARVI.

The duration of cough at inclusion in the trial should be at least 24 hours but not more than 72 hours; cough severity - 6 or more points (according to the Cough Severity Score (CSS)).

After one of the parents/adoptive parents signs the patient information leaflet (PIL) and the informed consent form (ICF) (two versions are used - with the consent of the parent/adoptive parent to take blood and urine samples for the purpose of conducting laboratory tests or without consent) for participation in the clinical trial at Visit 1, complaints and anamnesis are collected, vital signs are assessed, a physical examination is performed, concomitant therapy is recorded, and laboratory tests are conducted.

It is planned to conduct a general urine analysis, general and biochemical blood tests in at least 50% of patients.

At Visit 1, the physician together with the parent/adoptive parent fills out the CSS scale.

If inclusion criteria are met and there are no any exclusion criteria at Visit 1 (Day 1), the patient is enrolled in the study and randomized to one of two groups: Group 1 patients will receive Rengalin; Group 2 patients will receive Placebo.

After three days of the study therapy, at Visit 2 (Day 4), the physician evaluates the patient's condition and adjusts the therapy. If there are indications (secretion of viscous sputum), the physician prescribes the mucolytic ambroxol; at the same time, patients of group 1 continue taking Rengalin, and patients of group 2 continue taking Placebo.

The study will use an electronic patient diary (EPD) in which the parent/adoptive parent will record the severity of daytime and nighttime cough as measured by the CSS during the 7 days the patient is in the study. In addition, any possible worsening of the patient's condition (if applicable) will be recorded in the EPD for safety assessment and recording of adverse events.The investigator will instruct parents/adoptive parents will instruct parents/adoptive parents on how to fill out the diary.

The parent/adoptive parent will make the first marks on the cough severity scale in the EDS together with the physician at Visit 1. The EPD will be available for completion throughout the patient's participation in the study. Twice a day, the parent/adoptive parent will receive an SMS reminder: "Please mark the severity of daytime and nighttime cough in the diary. Do not forget to take the medication given to you." The patient treatment continues for 7 days, observation - for 14 days (screening, randomization - 1 day, treatment - 7 days, follow-up - up to 14 days; delayed "phone visit" - 14 days).

On days 4 (Visit 2) and 8 (Visit 3), two visits are planned (at home or at a medical center), during which the physician collects complaints, records medical examination data, identifies possible bacterial complications of acute respiratory infections, monitors prescribed and concomitant therapy, evaluates the safety of the treatment, and checks the filling of the CSS in the EPD.

At Visit 3 (Day 8), samples are collected for laboratory testing. The study drug that the parent/adopter received at Visit 1 must be returned at Visit 3 to assess compliance with the study therapy.

If the patient's condition worsens, the doctor make an unscheduled visit. "Telephone visit" (Visit 4, Day 14±1) is conducted to interview parents/adoptive parents about the patient's condition, presence/absence of cough, bacterial complications of acute respiratory viral infections, and the possible use of antibacterial drugs.

During the study, the use of antiviral drugs, symptomatic agents, and drugs for the treatment of concomitant diseases is permitted, with the exception of drugs listed in the section "Prohibited concomitant therapy".

Inclusion Criteria:

1. Outpatients of both genders aged over 6 months and under 3 years.
2. Clinically confirmed diagnosis of acute viral upper respiratory tract infections (acute pharyngitis, nasopharyngitis, tonsillitis, laryngitis, laryngotracheitis, tracheitis, acute viral respiratory infection of multiple and unspecified localization) during the epidemic growth of influenza and ARVI.
3. Dry (non-productive) cough lasting at least 24 hours but not more than 72 hours.
4. Total (day and night) cough severity score of 6 or more.
5. Availability of a patient information sheet and an informed consent form for participation in the clinical trial signed by one of the patient's parents/adoptive parents.

Exclusion Criteria:

1. Presence of the following diseases at the time of inclusion in the clinical trial:

   1.1 Inflammatory processes in the lower respiratory tract. 1.2 Grade III adenoid hypertrophy. 1.3 Chronic adenoiditis. 1.4 Postnasal drip syndrome. 1.5 Gastroesophageal reflux. 1.6 Bronchial asthma. 1.7 Cystic fibrosis. 1.8 Primary ciliary dyskinesia 1.9 Bronchopulmonary dysplasia 1.10 Malformations of the respiratory and ENT organs 1.11 Other chronic lung diseases. 1.12 Primary/secondary immunodeficiency. 1.13 Oncological disease of any localization.

2. Suspected bacterial infection of any localization, including pneumonia, sinusitis, otitis media.

3. Allergic rhinitis.

4. Bronchial obstruction syndrome.

5. Acute obstructive laryngitis [croup] and epiglottitis.

6. Congenital heart defects with hypervolemia in pulmonary circulation.

7. Acute respiratory failure.

8. Inflammatory, degenerative, demyelinating diseases of the central nervous system, polyneuropathies, epilepsy.

9. Exacerbation or decompensation of chronic diseases affecting the patient's ability to participate in a clinical trial.

10. Presence of allergy/hypersensitivity to any components of the medicines used in the treatment.

11. Taking medications listed in the section "Prohibited Concomitant Therapy" within 4 weeks prior to inclusion in the study.

12. Patients whose parents/adoptive parents, from the investigator's point of view, will not comply with observation requirements during the study or with the administration of study drugs.

13. Participation in other clinical trials within 3 months prior to inclusion in this trial.

14. A patient's parent/adoptive parent 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.

15. The patient's parent/adoptive parent 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.