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Background
Maintenance inhaled treatment of chronic obstructive pulmonary disease (COPD) is based on long-acting ?2-agonist (LABA) and/or long-acting muscarinic antagonists (LAMA) and LABA/inhaled corticosteroid (ICS) [1]. Despite treatment, most of the patients remain symptomatic, requiring a change in therapy [2].
A once-daily (q.d.) combination of indacaterol and glycopyrronium (IND/GLY) was effective and well tolerated in patients with moderate-to-severe COPD in several phase III trials [3, 4]. Such pivotal trials are usually performed in selected patients and hospital settings [5]. Patients with COPD treated in primary care settings often differ from those included in large randomised controlled trials (RCTs) [6]. Moreover, in RCTs, prior to randomisation, patients typically go through a washout period, in contrast to clinical practice where treatment changes occur without any washout period [5]. The effectiveness of a treatment in clinical practice can be evaluated more appropriately in a direct switch study in primary care settings, engaging a relevant patient pool with less stringent inclusion criteria [6].
CRYSTAL (effect of glyCopyrronium or indacateRol maleate and glYcopyrronium bromide fixed-dose combination [FDC] on SympToms and heALth status in patients with moderate COPD) was a 12-week, prospective, multi-centre, open-label study carried out in clinical practice settings to evaluate the impact of a direct switch to GLY or IND/GLY from previous standard-of-care treatments on lung function and dyspnoea in symptomatic patients with moderate COPD.
In this manuscript, we focus on the fully recruited and adequately powered groups directly switched to IND/GLY; the results of the GLY groups are described in the Additional file 1: Section S6, Tables S1, S2, S3 and S4 and Figures S5 and S6.
Methods
Study design and patients
CRYSTAL was a prospective, multi-centre, 12-week, randomised, open-label, pragmatic study, designed to evaluate the effectiveness and safety of GLY or IND/GLY after a direct switch from previous treatments in clinical settings in patients with moderate COPD. The study comprised a 30-day safety follow-up period, conducted from June 2014 to April 2016 at 560 sites across 23 countries in Europe, in both hospital and primary care settings (Fig. 1 and Additional file 1: Figure S1). [ Table Omitted - see PDF ]
Fig. 1
CRYSTAL study design (groups switched to IND/GLY). *Free or fixed-dose combination. †Randomisation ratio (switched: baseline treatments) = 3:1 by stratifying background medications....