FLAME (indacaterol/glycopyrronium)
Trial question
What is the role of indacaterol/glycopyrronium in patients with COPD who have high risk of exacerbations?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
24.0% female
76.0% male
N = 3362
3362 patients (805 female, 2557 male).
Inclusion criteria: patients who had COPD with a history of at least one exacerbation during the previous year.
Key exclusion criteria: T1DM or uncontrolled T2DM; history of long QT syndrome; clinically significant ECG abnormality; clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities.
Interventions
N=1680 indacaterol and glycopyrronium (indacaterol at a dose of 110 mcg plus glycopyrronium at a dose of 50 mcg once daily by inhalation for 52 weeks).
N=1682 salmeterol and fluticasone (salmeterol at a dose of 50 mcg plus fluticasone at a dose of 500 mcg BID by inhalation for 52 weeks).
Primary outcome
Chronic obstructive pulmonary disease exacerbation
3.59 / p-y
4.03 / p-y
4.0/ p-y
3.0/ p-y
2.0/ p-y
1.0/ p-y
0.0/ p-y
Indacaterol and
glycopyrronium
Salmeterol and
fluticasone
Significant
decrease ▼
Significant decrease in COPD exacerbation (3.59/ p-y vs. 4.03/ p-y; RR 0.89, 95% CI 0.83 to 0.96).
Secondary outcomes
Significantly shorter time to first exacerbation (71 days vs. 51 days; HR 0.84, 95% CI 0.78 to 0.91).
Significant decrease in moderate or severe exacerbations (0.98 vs. 1.19; RR 0.83, 95% CI 0.75 to 0.91).
Significantly shorter time to first moderate or severe exacerbation (127 days vs. 87 days; HR 0.78, 95% CI 0.7 to 0.86).
Safety outcomes
No significant difference in incidence of adverse events and deaths.
Significant difference in pneumonia (3.2% vs. 4.8%).
Conclusion
In patients who had COPD with a history of at least one exacerbation during the previous year, indacaterol and glycopyrronium were superior to salmeterol and fluticasone with respect to COPD exacerbation.
Reference
Wedzicha JA, Banerji D, Chapman KR et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. 2016 Jun 9;374(23):2222-34.
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