"Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD". The New England Journal of Medicine. 2016. PubMed•Full text•PDF

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

Clinical Question

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?

Bottom Line

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.

Major Points

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.

Guidelines

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.

Design

Multicenter, randomized, double-blind, double-dummy, parallel-group, noninferiority trial.

Population

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.

Interventions

Indacaterol (110 μg) plus glycopyrronium (50 μg) once daily compared with salmeterol (50 μg) plus fluticasone (500 μg) twice daily for 52 weeks.

Outcomes

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.

Secondary Outcomes
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.

Criticisms

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.

Funding

The FLAME trial was supported by Novartis.

Further Reading

More information and a complete list of investigators in the FLAME trial can be found at NEJM.org and ClinicalTrials.gov (NCT01782326).