Clinical Trial of Efficacy and Safety of Rengalin in the Treatment of Cough in Patients With Chronic Obstructive Pulmonary Disease

Multicenter Double-blind Placebo-controlled Parallel-group Randomized Clinical Trial of Efficacy and Safety of Rengalin in the Treatment of Cough in Patients With Chronic Obstructive Pulmonary Disease

The purpose of this study is to obtain additional data on efficacy and safety of Rengalin in the treatment of cough in patients with stable obstructive pulmonary disease

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Rengalin; Drug: Placebo

Detailed Description

Design: multicenter, double-blind, randomized, parallel group placebo-controlled study.

The study will enroll men and women (aged 40 to 80 years) with cough associated with stable chronic obstructive pulmonary disease (COPD). Subjects with COPD diagnosed more than 12 months earlier obtaining allowed basic therapy and retaining cough ≥2 points (according to cough severity scale [CSS]) despite their therapy should be considered as the study candidates.

After signing patient information leaflet (informed consent form) to participate in the clinical study, collection of medical history and objective examination are performed, cough severity is assessed (using CSS; at baseline evaluation of diurnal and nocturnal cough the number of episodes and cough severity in the preceding day is taken into account) as well as intensity of COPD effect on the subject (САТ test), concomitant therapy is recorded, computer spirometry with evaluation of baseline FEV1/FVC and post-bronchodilator FEV1 (where respiratory function cannot be assessed, the results of the previous examination dating no more than 3 months earlier may be used). Females of childbearing potential will undergo pregnancy test.

If a patient meets the inclusion criteria and does not demonstrate any of the exclusion criteria at Visit 1 (Day 1), he/she is randomized to one of 2 groups: group 1 patients will receive Rengalin at 2 tablets 3 times a day for 4 weeks; group 2 patients will receive placebo using Rengalin dosing regimen for 4 weeks.

The patient will be monitored for 4 weeks (screening, randomization - before day 1, treatment - 4 weeks). During follow-up period two visits are scheduled (Visit 1 (Day 1) and Visit 2 (Week 4) at which objective examination, recording cough severity (using CSS) will be carried out, COPD effect on the subjects (САТ test) and concomitant therapy will be evaluated. At Visit 2 (after 4-week treatment period) compliance will be additionally assessed.

At one of the clinical sites (Research Institute of Pulmonology, Russian FMBA), patients will be monitored for cough on a daily basis (using the WHolter™ monitor), with the data used as an additional measure to evaluate efficacy.

Subjects are allowed to take basic COPD therapy and medications for their co-morbidities in the course of the study, except for the medicines listed in "Prohibited concomitant treatment".

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Barnaul, Russian Federation, 656024
    • Regional state budgetary health care institution "Regional Clinical Hospital"
  • Barnaul, Russian Federation, 656045
    • Regional state budget health care institution "City Hospital No. 5, Barnaul"
  • Chelyabinsk, Russian Federation, 454000
    • NUZ "Road Clinical Hospital at the station Chelyabinsk JSC" RZhD "
  • Chelyabinsk, Russian Federation, 454021
    • The State Budget Health Institution "Regional Clinical Hospital No. 4"
  • Kazan, Russian Federation, 420012
    • Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University"/Central City Clinical Hospital and Clinic #18
  • Kazan, Russian Federation, 420012
    • Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University"/Professor's Clinic
  • Moscow, Russian Federation, 117997
    • Pirogov Russian National Research Medical University
  • Nizhny Novgorod, Russian Federation, 603011
    • State Budgetary Institution of Health Care of the Nizhny Novgorod Region "City Clinical Hospital No. 10"
  • Ryazan, Russian Federation, 390026
    • Ryazan State Medical University named after academician I.P. Pavlov
  • Saint Petersburg, Russian Federation, 191015
    • North-Western state Medical University named after I.I. Mechnikov
  • Saint Petersburg, Russian Federation, 191015
    • North-Western State Medical University named after I.I.Mechnikov
  • Saint Petersburg, Russian Federation, 191180
    • St. Petersburg State Budgetary Public Health Institution "Vvedensky City Clinical Hospital"
  • Saint Petersburg, Russian Federation, 194044
    • The Federal State Institute of Public Health 'The Nikiforov Russian Center of Emergency and Radiation Medicine'
  • Saint Petersburg, Russian Federation, 197022
    • The First Pavlov State Medical University of St. Petersburg
  • Saint Petersburg, Russian Federation, 198328
    • St. Petersburg State Budgetary Institution of Health "City Polyclinic No. 106"
  • Samara, Russian Federation, 443056
    • Samara City Hospital №4
  • Sestroretsk, Russian Federation, 197706
    • St. Petersburg State Budgetary Institution "City Hospital No. 40 in the Kurortny District"
  • Voronezh, Russian Federation, 394066
    • Voronezh Regional Clinical Hospital №1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients of both sexes aged from 40 to 80 years old.
2. COPD diagnosed (in accordance with the GOLD-2014 guidelines) ≥12 months before inclusion.
3. Stable course of COPD (≥ 6 weeks free of disease progression).
4. Mild, moderate or severe degree of bronchial obstruction (FEV1/FVC < 0.7; post-bronchodilator FEV1 ≥30% of predicted value).
5. CSS score ≥2.
6. Stable dose of standard therapy within the preceding 4 weeks.
7. Use of and adherence to contraceptive methods by fertile-age patients of both sexes during the study.
8. Availability of a signed patient information sheet (Informed Consent form) for participation in the trial.

Exclusion Criteria:

1. Earlier diagnosis of intra- or extrathoracic causes of cough (e.g., asthma, malignant neoplasm of lung, tuberculosis, sarcoidosis, α1-antitrypsin deficiency, bronchiectasis, cystic fibrosis, interstitial pulmonary diseases, perennial allergic rhinitis, gastro-oesophageal reflux disease, use of ACE inhibitors, disease of upper respiratory tract, etc.).
2. Cough associated with eating.
3. An exacerbation of COPD, acute upper and/or lower respiratory infection at inclusion or in the previous 4 weeks.
4. Modifications to standard drug therapy (dose escalation, replacement of medicines prescribed or addition of new medications) in the previous 4 weeks.
5. Very severe degree of bronchial obstruction (post-bronchodilator FEV1 <30% pred or < 50% and chronic respiratory failure).
6. Haemoptysis.
7. Stroke in the preceding 3 months or stroke with long-term residual neurological deficit within 6 months before study entry.
8. Acute coronary syndrome, myocardial infarction within 6 months before study enrollment.
9. Unstable or life-threatening arrhythmia in the previous 3 months.
10. Acute or chronic heart failure (NYHA (1964) Class III or IV).
11. Presence or suspicion of oncological disease.
12. Body Mass Index (BMI) ≤18 kg/m2 or ≥40 kg/m2.
13. Chronic kidney disease (categories С3-5 А3).
14. Hepatic failure (Child-Pugh class C)
15. Exacerbation or decompensation of a chronic disease that would affect the patient's ability to participate in the clinical trial.
16. For smokers - intention to quit smoking in the next 4 weeks.
17. Allergy/intolerance to any of the components of medications used in the treatment.
18. Course intake of medicines listed in the section 'Prohibited concomitant treatment' for 4 weeks prior to the enrollment in the trial.
19. Participation in other clinical trials within 3 months prior to the enrollment in this study.
20. Patients who, from investigator's point of view, will fail to comply with the observation requirements of the trial or with the dosing regimen of the investigational drug.
21. Other conditions preventing the patient from normal participation (e.g., planned business or other trips).
22. Drug addiction, alcohol use in the amount over 2 units of alcohol a day, mental diseases.
23. Pregnancy, breast-feeding, unwillingness to use contraception during the study.
24. Patient is related to the research staff of the clinical investigative site who are directly involved in the trial or is the immediate family member of the investigator. The immediate family members include husband/wife, parents, children or brothers (or sisters), regardless of whether they are natural or adopted.
25. Patient works for MATERIA MEDICA HOLDING company (i.e., is the company's employee, temporary contract worker or appointed official responsible for carrying out the research or their immediate family).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rengalin; Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal).	Drug: Rengalin; Oral administration.
Placebo Comparator: Placebo; Oral administration. Two tablets per intake. The tablet should be held in the mouth until complete dissolution. 2 tablets 3 times a day without food (i.e. 15-30 min prior to meal or 15-30 min after meal).	Drug: Placebo; Oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With a Positive Treatment Response	Cough Severity Scale (CSS) total score. Cough intensity according to the scale is assessed in daytime and at night in points where 0 - no cough, 5 - continuous exhausting cough in daytime and at night. Response criterion: ≥1 lower total CSS score compared to baseline.	in 4 weeks of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Cough After 4 Weeks Compared to Baseline	Cough Severity Scale (CSS) total score. Cough intensity according to the scale is assessed in the daytime and at night in points, where 0 - no cough, 5 - continuous exhausting cough in the daytime, and at night.	Baseline and 4 weeks after the treatment
Percentage of Patients With ≥50% Lesser Cough Severity at 4 Weeks	Number of Participants with a Decrease from Baseline of ≥50% in Cough Severity at 4 weeks. Based on the total Cough Severity Scale (CSS) score. Cough intensity according to the scale is assessed in the daytime and at night in points, where 0 - no cough, 5 - continuous exhausting cough in the daytime and at night.	in 4 weeks of the treatment
Changes in Clinical Symptoms of Chronic Obstructive Pulmonary Disease (COPD)	Based on the total COPD Assessment Test (CAT) score. CAT consists of 8 items. Each item ranges from "0" to "5" balls. The total score ranges from minimum "0" to maximum "40" points. Higher values represent a worse outcome.	in 4 weeks of the treatment
Percentage of Patients With no Exacerbation of COPD	COPD exacerbation is defined as an acute event characterized by aggravation of the event within 2-3 or more days. Exacerbation manifests in intensification of respiratory disorders beyond their regular daily fluctuations and require administration of products in addition to the previously prescribed basic therapy as well as a rescue drug for symptom relief (salbutamol). Additional products include antibacterial drugs, systemic corticosteroids and/or emergency therapy (ambulance call) or hospitalization for COPD exacerbation. COPD exacerbation is recorded as an adverse event. If a COPD exacerbation develops within the first week of the subject participation in the study, it will not be considered as a secondary inefficacy criterion	in 4 weeks of the treatment

Collaborators and Investigators

• Sponsor: Materia Medica Holding

Publications and helpful links

General Publications

• Avdeev SN, Vizel AA, Abrosimov VN, Zaicev AA, Ignatova GL, Khamitov RF, Mikhaylusova MP, Shapovalova JS, Pavlysh EF, Trofimov BI, Emelyanov AV, Martynenko TI, Martynenko VA, Kostina NE, Chizhov DA, Chizhova OY, Kuzubova NA, Makova EV, Makarova EV. Management of Cough in Patients with Chronic Obstructive Pulmonary Disease: Results of the Multicenter Randomized Placebo-Controlled Clinical Trial. Int J Chron Obstruct Pulmon Dis. 2021 May 5;16:1243-1253. doi: 10.2147/COPD.S292109. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2017
• Primary Completion (Actual): April 25, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (Actual): May 18, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: MMH-RN-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No