Management of Cough in Patients with Chronic Obstructive Pulmonary Disease: Results of the Multicenter Randomized Placebo-Controlled Clinical Trial

Abstract

Background: Chronic cough declines quality of life and increases risk of complications in patients with chronic obstructive pulmonary disease (COPD). Reducing cough severity and associated negative effects is important therapeutic goal in COPD. Rengalin with anti- and protussive activity is based on technologically processed antibodies to bradykinin, histamine and morphine.

Aim: To evaluate efficacy and safety of Rengalin in treatment of cough in patients with COPD.

Methods: Patients (n=238, mean age 64.3±8.2 years) with stable COPD and persistent cough despite maintenance therapy (anticholinergics, beta-2-adrenergic agonists, inhaled corticosteroids) were included and randomized in the study. The severity of cough assessment (according to the "Cough Severity Score"), COPD impact on patient's life (COPD Assessment Test, CAT), and spirometry were performed at screening. Patients took Rengalin or Placebo 2 tablets 2 times daily for 4 weeks. The endpoints were proportion of patients who responded to treatment, dynamics of cough severity, and severity of COPD symptoms. Intention-to-treat (per protocol) analysis was performed.

Results: Positive response to Rengalin was recorded in 83.6 [85.7]% (vs 72.6 [72.7]% in Placebo group, p=0.0422 [p=0.0163]). Double decrease of cough severity was reported in 42.2 [43.8]% in Rengalin group (versus 32.7 [32.7]% in Placebo; p=0.1373 [p=0.0907]). The total CAT score decreased by 3.3±4.2 [3.6±3.9] points (versus 2.5±4.1 [2.5±4.2] in Placebo group); the difference between groups was 0.79±4.16 [1.04±4.02] points (p=0.0870 [p=0.0416]). The number of patients with adverse events (AEs) in Rengalin (n=13) and Placebo (n=12) groups did not have significant differences (p=1.00). No AEs with certain relationship with study drug were registered.

Conclusion: Rengalin is an effective and safe drug in patients with stable COPD and persistent cough, despite stable doses of maintenance therapy according to the GOLD guidelines. Four-week therapy decreases severity of cough by two times in more than 40% of patients.

Trial registration: ClinicalTrials.gov (id: NCT03159091).

Keywords: Rengalin; chronic obstructive pulmonary disease; cough; cough management; treatment.

Conflict of interest statement

Avdeev S.N., MD, PhD, professor, Vizel’ A.A., MD, PhD, professor, Abrosimov V.N., MD, PhD, professor, Ignatova G.L., MD, PhD, professor, Khamitov R.F., MD, PhD, professor, Mikhaylusova M.P., MD, PhD, Shapovalova Yu.S., MD, PhD, Pavlysh E.F., MD, PhD, Trofimov V.I., MD, PhD, professor, Emel’yanov A.V., MD, PhD, professor, Martynenko T.I., MD, PhD, professor, Martynenko V.A., MD, PhD, Kostina N.E., MD, PhD, Chizhov D.A., MD, Chizhova O.Yu., MD, PhD, professor, Kuzubova N.A., MD, PhD, Makova E.V., MD, PhD, and Makarova E.V., MD, PhD received an investigator grant from Materia Medical Holding to conduct the clinical trial of Rengalin mentioned in this article. The authors report no other conflicts of interest in this work.

© 2021 Avdeev et al.

Figures

Figure 1

Flow diagram.

Figure 2

Percentage of patients responsive to treatment. PP analysis data. *p=0.016.

Figure 3

The change of the total CAT score after 4 weeks of treatment. PP analysis data. *p=0.0416.