Severe chronic obstructive pulmonary disease: once-daily Indacaterol versus Tiotropium
Researchers have compared the efficacy and safety of Indacaterol ( Arcapta Neohaler, Onbrez Breezhaler ) and Tiotropium ( Spiriva ) in patients with severe chronic obstructive pulmonary disease ( COPD ) and a history of at least one moderate to severe exacerbation in the previous 12 months.
In this multicentre, randomised, blinded, double-dummy, parallel group study ( INVIGORATE ), researchers enrolled patients aged 40 years or older with severe COPD and at least one exacerbation within the previous year.
Investigators have used a computer-generated sequence to randomly allocate patients ( 1:1; stratified by baseline inhaled corticosteroid use, with the balance of treatments maintained at country level ) to receive either Indacaterol ( 150 mcg ) or Tiotropium ( 18 mcg ) once-daily for 52 weeks.
The primary and key secondary objectives were to investigate whether Indacaterol was non-inferior to Tiotropium for trough forced expiratory volume in 1 s ( FEV1 ) at week 12 ( primary endpoint ), and for rate of exacerbations at week 52 ( secondary endpoint ).
Analysis populations for the primary and key secondary endpoints were per-protocol sets.
The safety set included all patients who received at least one dose of study drug.
During the period 2009-2012, researchers enrolled and randomly allocated 3444 patients: 1723 to Indacaterol and 1721 to Tiotropium.
At week 12, the estimated least squares mean trough FEV1 difference between the groups was -0.011 L ( least squares mean with Indacaterol [ n=1450 ] 1.134 L vs Tiotropium [ n=1467 ] 1.145 L; one-sided 97.5% CI lower limit -0.026 L; p less than 0.0001 ).
The lower limit of the 97.5% CI was above the prespecified non-inferiority margin of -0.055 L, suggesting that Indacaterol was non-inferior to Tiotropium.
Indacaterol did not show non-inferiority in terms of annualised exacerbation rates: 0.79 ( Indacaterol, n=1529 ) versus 0.61 ( Tiotropium, n=1543 ); ratio 1.29 ( one-sided 97.5% CI upper limit 1.44 ).
In the safety set, investigators recorded no between-group difference in the number of patients who had adverse events ( Indacaterol 1119 [ 65% ] of 1721 patients vs Tiotropium 1065 [ 62% ] of 1718 patients ) or serious adverse events ( Indacaterol, 263 [ 15% ] of 1721 patients vs Tiotropium, 255 [ 15% ] of 1718 patients ).
Respiratory disorders, particularly worsening of COPD, were the most common adverse events ( COPD: Indacaterol, 747 [ 43% ] of 1721 patients and Tiotropium, 665 [ 39% ] of 1718 patients ) and serious adverse events ( COPD: Indacaterol, 147 [ 9% ] of 1721 patients and Tiotropium, 121 [ 7% ] of 1718 patients ).
In conclusion, Indacaterol and Tiotropium have provided clinically relevant improvements in lung function with comparable safety profiles.
Tiotropium afforded greater protection from exacerbations, although the absolute number of events was small and the difference between treatments is of uncertain clinical importance.
The present data offer evidence consistent with current guidelines. ( Xagena )
Decramer ML et al, The Lancet Respiratory Medicine 2013; 1: 524-533