"Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD". The New England Journal of Medicine. 2016. PubMed•Full
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Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading
Among patients with COPD who have a history of at least one exacerbation in the previous year, is the LABA–LAMA regimen of indacaterol–glycopyrronium superior to the LABA–inhaled glucocorticoid regimen of salmeterol–fluticasone in preventing COPD exacerbations?
Indacaterol–glycopyrronium was more effective than salmeterol–fluticasone in preventing COPD exacerbations in patients with a history of exacerbations during the previous year, without an increase in adverse events.
The FLAME trial compared the effectiveness of the LABA–LAMA regimen (indacaterol–glycopyrronium) against the LABA–inhaled glucocorticoid regimen (salmeterol–fluticasone) in preventing COPD exacerbations. The trial demonstrated the superiority of indacaterol–glycopyrronium with consistent benefits across all outcomes related to exacerbations, lung function, and health status. This trial has potential implications for COPD treatment guidelines, supporting first-line use of a LABA–LAMA regimen for patients at risk for exacerbations.
As of 2016, treatment guidelines recommended either LABA plus inhaled glucocorticoid or LAMA to prevent COPD exacerbations in high-risk patients. The results of the FLAME trial suggest possible changes to these recommendations favoring LABA–LAMA regimens.
Multicenter, randomized, double-blind, double-dummy, parallel-group, noninferiority trial.
In total, 3,362 patients were randomly assigned to either treatment group.
Inclusion Criteria Patients with a history of ≥1 COPD exacerbation in the previous year, a post-bronchodilator FEV1 ≥25% to <60% predicted, and a post-bronchodilator FEV1/FVC <0.70.
Exclusion Criteria Major exclusion criteria included current malignancy, significant comorbidity limiting life expectancy, and a history of asthma.
Baseline Characteristics Patients had moderate to severe airflow limitation; over half were using inhaled glucocorticoids at screening.
Indacaterol (110 μg) plus glycopyrronium (50 μg) once daily compared with salmeterol (50 μg) plus fluticasone (500 μg) twice daily for 52 weeks.
Primary Outcome The primary outcome was the annual rate of all COPD exacerbations. Indacaterol–glycopyrronium demonstrated both noninferiority and superiority to salmeterol–fluticasone, with an 11% lower rate.
Indacaterol–glycopyrronium significantly prolonged the time to the first COPD exacerbation and decreased the annual rate of moderate or severe exacerbations compared with salmeterol–fluticasone. Improvements in lung function and health status were also observed with indacaterol–glycopyrronium.
Potential for withdrawal effects in the indacaterol–glycopyrronium group from prior long-term inhaled glucocorticoid use. Different daily dosing regimens of the two treatment arms may favor the once-daily LABA–LAMA group.
The FLAME trial was supported by Novartis.
More information and a complete list of investigators in the FLAME trial can be found at NEJM.org and ClinicalTrials.gov (NCT01782326).