Clinical trial NCT03159091: Clinical Trial of Efficacy and Safety of Rengalin in the Treatment of Cough in Patients With Chronic Obstructive Pulmonary Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Materia Medica Holding
Sponsor class: INDUSTRY
First posted: 2017-05-18
Enrollment: 238
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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".

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of Patients With a Positive Treatment Response
timeFrame: in 4 weeks of the treatment
Secondary outcomes:
measure: Severity of Cough After 4 Weeks Compared to Baseline
timeFrame: Baseline and 4 weeks after the treatment
measure: Percentage of Patients With ≥50% Lesser Cough Severity at 4 Weeks
timeFrame: in 4 weeks of the treatment
measure: Changes in Clinical Symptoms of Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: in 4 weeks of the treatment
measure: Percentage of Patients With no Exacerbation of COPD
timeFrame: in 4 weeks of the treatment
Other outcomes:
Locations:
city: Barnaul
country: Russian Federation
facility: Regional state budgetary health care institution "Regional Clinical Hospital"
city: Barnaul
country: Russian Federation
facility: Regional state budget health care institution "City Hospital No. 5, Barnaul"
city: Chelyabinsk
country: Russian Federation
facility: NUZ "Road Clinical Hospital at the station Chelyabinsk JSC" RZhD "
city: Chelyabinsk
country: Russian Federation
facility: The State Budget Health Institution "Regional Clinical Hospital No. 4"
city: Kazan
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University"/Central City Clinical Hospital and Clinic #18
city: Kazan
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University"/Professor's Clinic
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
city: Nizhny Novgorod
country: Russian Federation
facility: State Budgetary Institution of Health Care of the Nizhny Novgorod Region "City Clinical Hospital No. 10"
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University named after academician I.P. Pavlov
city: Saint Petersburg
country: Russian Federation
facility: North-Western State Medical University named after I.I. Mechnikov
city: Saint Petersburg
country: Russian Federation
facility: North-western State Medical University named after I.I.Mechnikov
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Public Health Institution "Vvedensky City Clinical Hospital"
city: Saint Petersburg
country: Russian Federation
facility: The Federal State Institute of Public Health 'The Nikiforov Russian Center of Emergency and Radiation Medicine'
city: Saint Petersburg
country: Russian Federation
facility: The First Pavlov State Medical University of St. Petersburg
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Institution of Health "City Polyclinic No. 106"
city: Samara
country: Russian Federation
facility: Samara City Hospital №4
city: Sestroretsk
country: Russian Federation
facility: St. Petersburg State Budgetary Institution "City Hospital No. 40 in the Kurortny District"
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Hospital №1
Study officials:
References:
citation: 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.