Observational, Concurrent Study to Assess Safety and Efficacy of Glycopyrronium and Arformoterol Home Nebulization in High-risk, Symptomatic Acute Exacerbation of Chronic Obstructive Pulmonary Disease Cases: SYMPTOM Study

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is one of the most important reasons for hospitalizationworldwide with high 30-day readmission rates. Although the prognostic significance of early readmission is not fully understood,they are often associated with poor outcomes including high mortality rates of 4%–19% at 30 and 365 days, respectively.Similarly, in acute exacerbations of COPD (AECOPD) cases receiving emergency department care, current status on lungfunction and cardiovascular comorbidities are considered as best predictors for both 30- and 90-day COPD readmission rates.Dual bronchodilator strategy with long-acting muscarinic antagonist (LAMA)/long-acting beta-agonists (LABA) is thereforerecommended by GOLD (2019) in the postdischarge phase following an acute exacerbation.Aim: To further assess the clinical impact of dual bronchodilators including glycopyrronium and arformoterol as home nebulizationin the post-discharge phase of AECOPD, the current postapproval, observational study was conducted.Materials and Methods: An observational, concurrent, and non-inferiority study with glycopyrronium and arformoterol homenebulizing solutions on patients with moderate and severe COPD was conducted at two centers in India. An estimated samplesize of 40 patients involving moderate and severe COPD cases was factored for per-protocol analyses with P < 0.05 consideredas statistically significant. A concurrent study analysis for the follow-up visit was conducted as per the principles of InternationalConference of Harmonization for Good clinical practice and Declaration of Helsinki while ensuring confidentiality during accessof patient support registration sheets.Results: Per protocol analyses for consecutive 46 cases from two centers receiving Nebulized glycopyrronium (25 mcg) andarformoterol (15 mcg), as separate formulations are given as admixed solution with follow-up visit for at least 4 weeks wascarried out. Baseline demographics for the overall group showed exacerbation history (46, 100%), hospitalization for AECOPD(21, 45.6%); ED visit (25, 54.3%), forced expiratory volume in one second (FEV1) 1.2 ± 0.6 L/min; FEV1/FVC64.8% ± 10.6;reversibility 8.4% ± 11.8; CAT 34.6 ± 2.3; and vibrating mesh nebulizer (46, 100%). The mean predose FEV1 (∆) at the end of 4weeks for overall, moderate and severe COPD cases were observed as of 9.6±3.1%, 11.8% ± 3.1, and 8.4% ± 1.6, respectively(P < 0.0001). Similarly, the mean CAT(∆) score at the end of 4 weeks was observed as of 18.1 ± 0.69, 20.6 ± 0.69, and 18.26 ±0.6 for overall, moderate and severe COPD cases, respectively (P < 0.0001). The intergroup differences for rescue medicationuse for a lone case with severe COPD (1, 2.04%) complied with the suggested non-inferiority margin between the groups.There were no other treatment-emergent adverse events or serious adverse events that warranted treatment modification orwithdrawals in both groups.