ArticlesOnce-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study
Introduction
Long-acting inhaled bronchodilators used for treatment of stable chronic obstructive pulmonary disease (COPD) include two classes of pharmacological agents: long-acting β2-agonists (LABA; eg, indacaterol) and long-acting muscarinic antagonists (LAMA; eg, tiotropium). Both tiotropium1 and indacaterol2 have shown clinically meaningful bronchodilation, symptomatic benefits, and improved health outcomes in patients with COPD, and both have acceptable safety profiles.
Higher rates of COPD exacerbations have previously been associated with impaired health-related quality of life3, 4 and a more rapid decrease in lung function.5, 6 The mechanical effects of an exacerbation are complex, involving worsening airflow limitation, increases in dynamic hyperinflation, and increased end-expiratory lung volume and residual volume.7 Bronchodilators improve airflow limitation and reduce breathlessness, which might in part explain their effectiveness in preventing exacerbations.8
Findings from three studies comparing once-daily indacaterol (150 μg or 300 μg) with once-daily tiotropium (18 μg), all done in patients with moderate-to-severe airflow limitation (ie, ≥30% and <80% predicted forced expiratory volume in 1 s [FEV1]), have shown a faster onset of bronchodilation at first dose together with non-inferiority or superiority of indacaterol versus tiotropium with regards to trough FEV1.9, 10, 11 Dyspnoea, as measured with the Transition Dyspnoea Index (TDI) total scores at week 12, was improved for once-daily indacaterol (300 μg) versus open-label tiotropium10 in one of these trials, and for indacaterol (150 μg) versus blinded tiotropium in another.9 Once-daily indacaterol (150 μg) improved health status (as shown by improving St George's Respiratory Questionnaire [SGRQ] total scores) at week 12 versus tiotropium in both trials.9, 10
For patients who are at increased risk of exacerbations (eg, patients with greater airflow limitation or those with a history of exacerbations), prevention of exacerbations is a key treatment goal of COPD disease management.12 We therefore assessed the effect of indacaterol on exacerbations in a long-term, blinded study in patients with severe COPD and a history of exacerbations, versus tiotropium, a bronchodilator with long-term efficacy on exacerbations.13, 14
Section snippets
Study design
INVIGORATE (indacaterol: providing opportunity to re-engage patients with life) was a 52 week, international, multicentre (408 centres in 41 countries, appendix), randomised, blinded, double-dummy, parallel group study comparing the effects of once-daily indacaterol maleate (150 μg) and tiotropium bromide (18 μg) on lung function, exacerbations and related outcomes in about 3500 patients with COPD and severe airflow limitation.15
We enrolled both men and women (aged ≥40 years) who had a smoking
Results
Between March 16, 2009, and July 5, 2012, we enrolled and randomly allocated 3444 patients: 1723 to indacaterol and 1721 to tiotropium (figure 1). Baseline characteristics were much the same between the treatment groups (table 1). Most patients were white men.
We recorded improvements from baseline in trough FEV1 in patients in both groups at week 12 (0·114 L with indacaterol and 0·126 L with tiotropium) and week 52 (0·073 L with indacaterol and 0·092 L with tiotropium).
At week 12, the estimated
Discussion
In this 1-year blinded comparison, once-daily treatment with indacaterol or tiotropium in patients with severe COPD and a history of exacerbations gave equally effective and clinically relevant improvements in lung function, health status, and breathlessness. Patients receiving indacaterol had a 29% higher rate of exacerbations versus patients receiving tiotropium, and a statistically significant 20% increase in the risk of the time to first COPD exacerbation. Compared with patients given
References (30)
- et al.
The measurement of dyspnea. Contents, interobserver agreement, and physiologic correlates of two new clinical indexes
Chest
(1984) - et al.
Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial
Lancet
(2003) - et al.
Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study
Lancet Respir Med
(2013) - et al.
Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target
Pulm Pharmacol Ther
(2013) - et al.
Beta(2) long-acting and anticholinergic drugs control TGF-beta1-mediated neutrophilic inflammation in COPD
Biochim Biophys Acta
(2012) - et al.
Effects of formoterol and tiotropium bromide on mucus clearance in patients with COPD
Respir Med
(2011) - et al.
Effects of salmeterol on cilia and mucus in COPD and pneumonia patients
Pharmacol Res
(2005) Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease
Drugs
(2012)Indacaterol: a review of its use as maintenance therapy in patients with chronic obstructive pulmonary disease
Drugs
(2012)- et al.
Time course of recovery of health status following an infective exacerbation of chronic bronchitis
Thorax
(2003)
Impact of preventing exacerbations on deterioration of health status in COPD
Eur Respir J
Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study
Am J Respir Crit Care Med
Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease
Thorax
COPD exacerbations. 3: Pathophysiology
Thorax
The role of bronchodilator tr.eatment in the prevention of exacerbations of COPD
Eur Respir J
Cited by (216)
Actualités concernant la prise en charge médicamenteuse de la BPCO
2022, Revue des Maladies Respiratoires ActualitesTake-home messages from the COPD 2021 biennial of the French Society of Respiratory Diseases. Understanding to so as to better innovate
2022, Revue des Maladies RespiratoiresCOPD inhaled therapy narrative review
2022, SemergenPharmacological Management of Asthma and COPD
2022, Comprehensive PharmacologySpanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD
2022, Archivos de Bronconeumologia