Effect of ELOM-080 on exacerbations and symptoms in COPD patients with a chronic bronchitis phenotype - a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial

Abstract

Background: Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease (COPD) long-term management. Recently, a more tailored treatment approach has been proposed, in particular for two well-established clinical phenotypes, frequent exacerbators and chronic bronchitis-dominant COPD. ELOM-080 has demonstrated clinical efficacy in treating symptoms and preventing exacerbations in subjects with chronic bronchitis. However, little is known about the potential effects of ELOM-080 in COPD patients.

Aim: To evaluate the effect on exacerbation, cough sputum, and general state of health of long-term treatment with ELOM-080 in COPD patients with an exacerbation history and chronic bronchitis.

Methods: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled parallel-group clinical trial of a 6-month treatment with ELOM-080 (3×300 mg) in patients with chronic bronchitis and concomitant COPD. The primary outcome was the proportion of subjects with at least one exacerbation over the 6-month study period. Secondary outcomes included the total number of exacerbations (ie, cumulative occurrence of exacerbations during the study period) and the proportion of acute exacerbations necessitating an antibiotic treatment, monthly evaluations of sputum and cough symptoms, and the general state of health and a safety analysis.

Results: Of 260 randomized subjects, 64 patients fulfilled the inclusion criteria for COPD (ELOM-080: 35, placebo: 29). Compared to placebo, ELOM-080 reduced the percentage of subjects with at least one exacerbation (29% versus 55%, P=0.031) and a reduction in the overall occurrence of exacerbations (ELOM-080: 10, placebo: 21, P=0.012) during the winter season. The percentage of asymptomatic or mildly symptomatic patients (sputum/expectoration and cough) was consistently higher in the ELOM-080 group compared to placebo, with statistical significant differences after 2 and 3 months of treatment (2 months: ELOM-080 25%, placebo 11%, P<0.005; 3 months: ELOM-080 26%, placebo 14%, P<0.05). Likewise the subjective rating of general health status was better in the ELOM-080 group with statistically significant superiority after 2 and 3 months of treatment (2-month treatment: P=0.015; 3-month treatment: P=0.024). Tolerability results were comparable between ELOM-080 and placebo.

Conclusion: ELOM-080 is efficacious in patients with COPD and a chronic bronchitis phenotype. Prophylactic use reduces the rate of exacerbations and improves the key symptoms of sputum and cough with a favorable long-term tolerability profile.

Keywords: COPD; chronic bronchitis; exacerbations; myrtol; phytotherapy; sputum; winter.

Figure 1

Flowchart of EAP identification. Notes: Of 260 subjects, 64 patients fulfilled the inclusion criteria for COPD. A COPD was considered, if a patient fit the criteria 1 (documented physician diagnosed COPD) or criteria 2+3+4 (FEV₁ ≤80% of the predicted value + concomitant bronchodilator ≥10 years treatment + smoking history). Abbreviations: COPD, chronic obstructive pulmonary disease; EAP, efficacy analyzable population; FEV₁, forced expiratory volume in 1 second.

Figure 2

Proportion of the subjects with at least one exacerbation after 6 months of treatment. Notes: Subjects treated with ELOM-080 showed a statistically significant lower exacerbation rate compared to placebo (ELOM-080: 29%, placebo: 55%, P=0.031).

Figure 3

Cumulative numbers of exacerbations during the treatment period. Notes: The ELOM-080 group had only few exacerbations in the beginning of the study period following by a stable exacerbation-free plateau phase. The placebo group is continuously affected by new exacerbations.

Figure 4

Number of patients without clinical impairment of cough and sputum. Notes: Patient treated with ELOM-080 were constantly less impaired by cough and sputum compared to placebo. A statistically significant difference was observed after 2 (P<0.005) and 3 months (P<0.05) of treatment. The impairment was rated by the patient in a 4-point scale (1= constantly bothered, 2= often bothered, while 3= rarely bothered, and 4= never bothered at all). All patients rating their symptoms with 3 or 4 points were considered as clinically not impaired.

Figure 5

Number of patients with a good or very good health status. Notes: Patients rating their general state of health consistently better in the ELOM-080 group compared to placebo. After 2 and 3 months of treatment the difference was statistically significant (2 months: P=0.015; 3 months: P=0.024).