Journal Article

Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial

Vogelmeier, Claus F., Castellani, Walter, Lane, Stephen, Nunez, Xavier, Patalano, Francesco, Kostikas, Konstantinos, Clemens, Andreas, Marin, Jose M., Greulich, Timm, Gaga, Mina, Aalamian-Mattheis, Maryam, Ninane, Vincent

2017

Overview

Background Dual bronchodilation combining a long-acting β 2 -agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials. Methods The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments. Results The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV 1 ; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV 1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies. Conclusions IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments. Trial registration ClinicalTrials.gov number: NCT01985334 .

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Acetylcholine receptors (muscarinic) / Adrenergic beta-2 Receptor Agonists - administration & dosage / Adrenergic beta-2 Receptor Agonists - adverse effects / Adult / Aged / Bronchodilation / Bronchodilator Agents - administration & dosage / Bronchodilator Agents - adverse effects / Bronchodilators / Chronic obstructive pulmonary disease / Clinical medicine / Clinical trials / Complications and side effects / Control methods / Corticosteroids / Direct switch / Disease control / Disease Progression / Dosage and administration / Drug Combinations / Drug Substitution / Drug therapy / Drug therapy, Combination / Dual bronchodilation / Dyspnea / Dyspnea - diagnosis / Dyspnea - drug therapy / Dyspnea - physiopathology / Europe / Female / Forced Expiratory Volume / Glycopyrrolate - administration & dosage / Glycopyrrolate - adverse effects / Health Status / Humans / Indacaterol / Indacaterol/glycopyrronium / Indans - administration & dosage / Indans - adverse effects / Lung - drug effects / Lung - physiopathology / Lung diseases / Lung diseases, Obstructive / Male / Medical research / Medicine / Medicine & Public Health / Middle Aged / Motivation / Muscarinic Antagonists - administration & dosage / Muscarinic Antagonists - adverse effects / Obstructive lung disease / Open-label / Patient outcomes / Patient Safety / Patients / Performance evaluation / Pneumology/Respiratory System / Primary care / Prospective Studies / Pulmonary Disease, Chronic Obstructive - diagnosis / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / Quality of Life / Quinolones - administration & dosage / Quinolones - adverse effects / Randomization / Recovery of Function / Respiration / Respiratory function / Risk Factors / Safety / Severity of Illness Index / Time Factors / Treatment Outcome