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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 May; 1(3):199-209.LR

Abstract

BACKGROUND

We evaluated the effect of dual, longacting inhaled bronchodilator treatment on exacerbations in patients with severe and very severe chronic obstructive pulmonary disease (COPD).

METHODS

In this parallel-group study, 2224 patients (aged ≥40 years, Global Initiative for Chronic Obstructive Lung Disease stages III-IV, and one or more moderate COPD exacerbation in the past year) were randomly assigned (1:1:1; via interactive voice response or web system; stratified for smoking status) to once-daily QVA149 (fixed-dose combination of indacaterol 110 μg and glycopyrronium 50 μg), glycopyrronium 50 μg, or tiotropium 18 μg for 64 weeks. Assignment to QVA149 and glycopyrronium was double-blind; tiotropium was open-label. Efficacy was assessed in all patients randomly assigned to treatment groups who received at least one dose of study drug; safety was assessed in all patients who received at least one dose whether or not they were assigned to a group. The primary objective was to show superiority of QVA149 versus glycopyrronium for rate of moderate to severe COPD exacerbations (defined by worsening symptoms and categorised by treatment requirements) during treatment. This completed trial is registered at ClinicalTrials.gov, NCT01120691.

FINDINGS

Between April 27, 2010, and July 11, 2012, 741 patients were randomly assigned to receive QVA149, 741 to receive glycopyrronium, and 742 to receive tiotropium (729, 739, and 737 patients, respectively, analysed for efficacy). QVA149 significantly reduced the rate of moderate to severe exacerbations versus glycopyrronium by 12% (annualised rate of exacerbations 0·84 [95% CI 0·75-0·94] vs 0·95 [0·85-1·06]; rate ratio 0·88, 95% CI 0·77-0·99, p=0·038). Adverse events (including exacerbations) were reported for 678 (93%) of 729 patients on QVA149, 694 (94%) of 740 on glycopyrronium, and 686 (93%) of 737 on tiotropium. Incidence of serious adverse events was similar between groups (167 [23%] patients on QVA149, 179 [24%] on glycopyrronium, and 165 [22%] on tiotropium); COPD worsening was the most frequent serious adverse event (107 [15%] patients on QVA149, 116 [16%] on glycopyrronium, 87 [12%] on tiotropium).

INTERPRETATIONS

The dual bronchodilator QVA149 was superior in preventing moderate to severe COPD exacerbations compared with the single longacting antimuscarinic bronchodilator glycopyrronium, with concomitant improvements in lung function and health status. These results indicate the potential of dual bronchodilation as a treatment option for patients with severe and very severe COPD.

FUNDING

Novartis Pharma AG.

Authors+Show Affiliations

Centre for Respiratory Medicine, University College London, Royal Free Campus, London, UK. Electronic address: w.wedzicha@ucl.ac.uk.Respiratory Division, University Hospitals, Leuven, Belgium.Paracelsus Medical University Nuremberg, Nuremberg, Germany; Klinikum Nuremberg, Department of Respiratory Medicine, Allergology, and Sleep Medicine, Nuremberg, Germany.University of Minnesota, Minneapolis VA Health Care Center, Pulmonary Section, Minneapolis, MN, USA.Umeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden.Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24429126

Citation

Wedzicha, Jadwiga A., 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." The Lancet. Respiratory Medicine, vol. 1, no. 3, 2013, pp. 199-209.
Wedzicha JA, Decramer M, Ficker JH, 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;1(3):199-209.
Wedzicha, J. A., Decramer, M., Ficker, J. H., Niewoehner, D. E., Sandström, T., Taylor, A. F., D'Andrea, P., Arrasate, C., Chen, H., & Banerji, D. (2013). 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. The Lancet. Respiratory Medicine, 1(3), 199-209. https://doi.org/10.1016/S2213-2600(13)70052-3
Wedzicha JA, 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;1(3):199-209. PubMed PMID: 24429126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wedzicha,Jadwiga A, AU - Decramer,Marc, AU - Ficker,Joachim H, AU - Niewoehner,Dennis E, AU - Sandström,Thomas, AU - Taylor,Angel Fowler, AU - D'Andrea,Peter, AU - Arrasate,Christie, AU - Chen,Hungta, AU - Banerji,Donald, Y1 - 2013/04/23/ PY - 2014/1/17/entrez PY - 2014/1/17/pubmed PY - 2014/2/22/medline SP - 199 EP - 209 JF - The Lancet. Respiratory medicine JO - Lancet Respir Med VL - 1 IS - 3 N2 - BACKGROUND: We evaluated the effect of dual, longacting inhaled bronchodilator treatment on exacerbations in patients with severe and very severe chronic obstructive pulmonary disease (COPD). METHODS: In this parallel-group study, 2224 patients (aged ≥40 years, Global Initiative for Chronic Obstructive Lung Disease stages III-IV, and one or more moderate COPD exacerbation in the past year) were randomly assigned (1:1:1; via interactive voice response or web system; stratified for smoking status) to once-daily QVA149 (fixed-dose combination of indacaterol 110 μg and glycopyrronium 50 μg), glycopyrronium 50 μg, or tiotropium 18 μg for 64 weeks. Assignment to QVA149 and glycopyrronium was double-blind; tiotropium was open-label. Efficacy was assessed in all patients randomly assigned to treatment groups who received at least one dose of study drug; safety was assessed in all patients who received at least one dose whether or not they were assigned to a group. The primary objective was to show superiority of QVA149 versus glycopyrronium for rate of moderate to severe COPD exacerbations (defined by worsening symptoms and categorised by treatment requirements) during treatment. This completed trial is registered at ClinicalTrials.gov, NCT01120691. FINDINGS: Between April 27, 2010, and July 11, 2012, 741 patients were randomly assigned to receive QVA149, 741 to receive glycopyrronium, and 742 to receive tiotropium (729, 739, and 737 patients, respectively, analysed for efficacy). QVA149 significantly reduced the rate of moderate to severe exacerbations versus glycopyrronium by 12% (annualised rate of exacerbations 0·84 [95% CI 0·75-0·94] vs 0·95 [0·85-1·06]; rate ratio 0·88, 95% CI 0·77-0·99, p=0·038). Adverse events (including exacerbations) were reported for 678 (93%) of 729 patients on QVA149, 694 (94%) of 740 on glycopyrronium, and 686 (93%) of 737 on tiotropium. Incidence of serious adverse events was similar between groups (167 [23%] patients on QVA149, 179 [24%] on glycopyrronium, and 165 [22%] on tiotropium); COPD worsening was the most frequent serious adverse event (107 [15%] patients on QVA149, 116 [16%] on glycopyrronium, 87 [12%] on tiotropium). INTERPRETATIONS: The dual bronchodilator QVA149 was superior in preventing moderate to severe COPD exacerbations compared with the single longacting antimuscarinic bronchodilator glycopyrronium, with concomitant improvements in lung function and health status. These results indicate the potential of dual bronchodilation as a treatment option for patients with severe and very severe COPD. FUNDING: Novartis Pharma AG. SN - 2213-2600 UR - https://www.unboundmedicine.com/medline/citation/24429126/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2600(13)70052-3 DB - PRIME DP - Unbound Medicine ER -