human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction Chronic obstructive pulmonary disease ( COPD ) is associated with increased cardiovascular morbidity and mortality . Elevated arterial stiffness , measured by aortic pulse wave velocity ( aPWV ) , is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD . Material s and methods The effects of once-daily inhaled fluticasone furoate/vilanterol ( FF/VI ) 100/25 µg , VI 25 µg , versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week , multicenter , double-blind , r and omized , stratified ( by COPD exacerbation history ) , parallel-group , placebo-controlled trial . Eligible patients were ≥40 years old , with ≥10 pack-year smoking history , forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70 , and post-bronchodilator FEV1 ≤70 % of predicted . Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded .  Primary endpoint is change from baseline in aPWV after 24 weeks of treatment . Safety analyses included adverse events ( AEs ) . Results The intent-to-treat population included 430 patients : FF/VI ( n=135 ) , VI ( n=154 ) , and placebo ( n=141 ) . Patients were predominantly male ( 79 % ) and Asian or White ( each 48 % ) , with a mean age of 68.5 years ( st and ard deviation [ SD ] = 7.9 ) , percentage predicted post-bronchodilator FEV1 50.1 % ( SD = 13.3 ) , and aPWV 13.26 m/s ( SD = 2.22 ) at screening . At 24 weeks , mean ( st and ard error [ SE ] ) changes from baseline in aPWV were −1.75 m/s ( SE = 0.26 , FF/VI ) , −1.95 m/s ( SE = 0.24 , VI ) , and −1.97 m/s ( SE = 0.28 , placebo ) . AEs occurred in 57 % ( FF/VI ) , 51 % ( VI ) , and 41 % ( placebo ) of patients . Conclusion No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg , compared with placebo We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium , tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . This was a multicentre , r and omised , double-blind , placebo- and active-controlled , 26-week trial . Patients ( n = 2144 ) were r and omised ( 2:2:2:2:1 ) to receive once-daily QVA149 ( indacaterol 110 & mgr;g/glycopyrronium 50 & mgr;g ) , indacaterol 150 & mgr;g , glycopyrronium 50 & mgr;g , open-label tiotropium 18 & mgr;g or placebo . The primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at week 26 for QVA149 versus its monocomponents . Secondary end-points included dyspnoea , health status , rescue medication use and safety . Trough FEV1 at week 26 was significantly improved ( p<0.001 ) with QVA149 compared with indacaterol and glycopyrronium ( least squares mean ( LSM ) differences 0.07 L and 0.09 L , respectively ) , tiotropium and placebo ( LSM differences 0.08 L and 0.20 L , respectively ) ; these beneficial effects were sustained throughout the 26-week study . QVA149 significantly improved dyspnoea and health status versus placebo ( p<0.001 and p = 0.002 , respectively ) and tiotropium ( p = 0.007 and p = 0.009 , respectively ) at week 26 . All treatments were well tolerated . Dual bronchodilation with once-daily QVA149 demonstrated superior and clinical ly meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator , with a safety and tolerability profile similar to placebo , supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting & bgr;2-agonist combinations for the treatment of COPD . Dual indacaterol/glycopyrronium therapy was safe and more efficacious than monotherapy in moderate-to-severe COPD Background The combination of the inhaled muscarinic antagonist umeclidinium ( UMEC ) with the long-acting β2-agonist vilanterol ( VI ) has been shown to provide significant improvements in lung function compared with UMEC , VI , or placebo ( PBO ) in patients with chronic obstructive pulmonary disease ( COPD ) . This study was specifically design ed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population . Methods This was a 12-week multicenter , r and omized , double-blind , parallel-group , placebo-controlled study . Eligible patients were r and omized 1:1 to receive once-daily UMEC/VI 62.5/25 μg ( via ELLIPTA ® dry powder inhaler ) or PBO for 12 weeks . The primary endpoint was St George ’s Respiratory Question naire ( SGRQ ) total score at day 84 . Secondary efficacy endpoints included rescue albuterol use ( puffs/day ) over weeks 1–12 and trough forced expiratory volume in 1 second on day 84 . Adverse events were also assessed . Results A total of 496 patients were included in the intent-to-treat population in the UMEC/VI ( n=248 ) and PBO ( n=248 ) treatment groups . UMEC/VI 62.5/25 μg provided a significant and clinical ly meaningful improvement in SGRQ total score at day 84 versus PBO ( difference between treatments in SGRQ total score change from baseline : −4.03 [ 95 % confidence interval { CI } : −6.28 , −1.79 ] ; P<0.001 ) . UMEC/VI 62.5/25 μg result ed in a statistically significant reduction in rescue albuterol use versus PBO ( −0.7 puffs/day [ 95 % CI : −1.1 , −0.4 ] ; P<0.001 ) . UMEC/VI 62.5/25 μg provided a significant and clinical ly meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO ( 122 mL [ 95 % CI : 71 , 172 ] ; P<0.001 ) . The incidence of adverse events was similar between treatments ( 32 % and 30 % of patients in the UMEC/VI 62.5/25 μg and PBO groups , respectively ) . Conclusion The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinical ly important improvements in SGRQ and rescue medication use  versus PBO in patients with moderate-to-very-severe COPD NVA237 ( glycopyrronium bromide ) is a once-daily long-acting muscarinic antagonist ( LAMA ) in development for chronic obstructive pulmonary disease ( COPD ) . The GLycopyrronium bromide in COPD airWays clinical Study 2 ( GLOW2 ) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks . Patients were r and omised 2:1:1 to NVA237 50 μg , placebo or open-label tiotropium 18 μg for 52 weeks . Primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at 12 weeks . 1,066 patients were r and omised , 810 completed the study . At week 12 , trough FEV1 increased significantly by 97 mL with NVA237 ( 95 % CI 64.6–130.2 ; p<0.001 ) and 83 mL with tiotropium ( 95 % CI 45.6–121.4 ; p<0.001 ) . Compared with placebo , NVA237 produced significant improvements in dyspnoea ( Transition Dyspnoea Index at week 26 ; p=0.002 ) and health status ( St George 's Respiratory Question naire at week 52 ; p<0.001 ) . NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34 % ( p=0.001 ) and the use of rescue medication ( p=0.039 ) , versus  placebo  . NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes . Safety profiles were similar across groups . NVA237 50 μg provided significant improvements in lung function , dyspnoea , health status , exacerbations and rescue medication use , versus placebo , and was comparable to tiotropium . NVA237 can potentially be an alternative choice of LAMA for COPD patients Background NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease ( COPD ) . The glycopyrronium bromide in COPD airways clinical study 1 ( GLOW1 ) evaluated the efficacy , safety and tolerability of NVA237 in patients with moderate-to-severe COPD . Methods Patients with COPD with a smoking history of ≥ 10 pack-years , post-bronchodilator forced expiratory volume in 1 second ( FEV1 ) < 80 % and ≥ 30 % predicted normal and FEV1/forced vital capacity < 0.70 were enrolled . Patients were r and omized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry . The primary outcome measure was trough FEV1 at Week 12 . Results A total of 822 patients were r and omized to NVA237 ( n = 552 ) or placebo ( n = 270 ) . Least squares mean ( ± st and ard error ) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 ( 1.408 ± 0.0105 L ) , versus placebo ( 1.301 ± 0.0137 L ; treatment difference 108 ± 14.8 mL , p < 0.001 ) . Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26 . FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26 , and at all other visits and timepoints . Transition dyspnoea index focal scores and St. George 's Respiratory Question naire scores were significantly improved with NVA237 versus placebo at Week 26 , with treatment differences of 1.04 ( p < 0.001 ) and -2.81 ( p = 0.004 ) , respectively  . NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31 % ( p = 0.023 ) and use of rescue medication by 0.46 puffs per day ( p = 0.005 ) , versus placebo . NVA237 was well tolerated and had an acceptable safety profile , with a low frequency of cardiac and typical antimuscarinic adverse effects . Conclusions Once-daily NVA237 was safe and well tolerated and provided rapid , sustained improvements in lung function , improvements in dyspnoea , and health-related quality of life , and reduced the risk of exacerbations and the use of rescue medication . Trial registration Clinical Trials.gov : BACKGROUND Fluticasone furoate/vilanterol ( FF/VI ) is an inhaled corticosteroid/long-acting beta2-agonist ( ICS/LABA ) , recently approved as once-daily maintenance therapy for COPD . We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol ( FP/SAL ) . METHODS Three 12 week studies comparing FF/VI and FP/SAL were conducted . Patients aged ≥40 years with moderate-to-very severe COPD were r and omized to receive double-blind , double-dummy FF/VI 100/25 mcg once-daily , or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period . The primary endpoint of each study was change from baseline trough in 0 - 24 h weighted mean FEV 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction Chronic obstructive pulmonary disease ( COPD ) is associated with increased cardiovascular morbidity and mortality . Elevated arterial stiffness , measured by aortic pulse wave velocity ( aPWV ) , is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD . Material s and methods The effects of once-daily inhaled fluticasone furoate/vilanterol ( FF/VI ) 100/25 µg , VI 25 µg , versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week , multicenter , double-blind , r and omized , stratified ( by COPD exacerbation history ) , parallel-group , placebo-controlled trial . Eligible patients were ≥40 years old , with ≥10 pack-year smoking history , forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70 , and post-bronchodilator FEV1 ≤70 % of predicted . Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded .  Primary endpoint is change from baseline in aPWV after 24 weeks of treatment . Safety analyses included adverse events ( AEs ) . Results The intent-to-treat population included 430 patients : FF/VI ( n=135 ) , VI ( n=154 ) , and placebo ( n=141 ) . Patients were predominantly male ( 79 % ) and Asian or White ( each 48 % ) , with a mean age of 68.5 years ( st and ard deviation [ SD ] = 7.9 ) , percentage predicted post-bronchodilator FEV1 50.1 % ( SD = 13.3 ) , and aPWV 13.26 m/s ( SD = 2.22 ) at screening . At 24 weeks , mean ( st and ard error [ SE ] ) changes from baseline in aPWV were −1.75 m/s ( SE = 0.26 , FF/VI ) , −1.95 m/s ( SE = 0.24 , VI ) , and −1.97 m/s ( SE = 0.28 , placebo ) . AEs occurred in 57 % ( FF/VI ) , 51 % ( VI ) , and 41 % ( placebo ) of patients . Conclusion No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg , compared with placebo We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium , tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . This was a multicentre , r and omised , double-blind , placebo- and active-controlled , 26-week trial . Patients ( n = 2144 ) were r and omised ( 2:2:2:2:1 ) to receive once-daily QVA149 ( indacaterol 110 & mgr;g/glycopyrronium 50 & mgr;g ) , indacaterol 150 & mgr;g , glycopyrronium 50 & mgr;g , open-label tiotropium 18 & mgr;g or placebo . The primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at week 26 for QVA149 versus its monocomponents . Secondary end-points included dyspnoea , health status , rescue medication use and safety . Trough FEV1 at week 26 was significantly improved ( p<0.001 ) with QVA149 compared with indacaterol and glycopyrronium ( least squares mean ( LSM ) differences 0.07 L and 0.09 L , respectively ) , tiotropium and placebo ( LSM differences 0.08 L and 0.20 L , respectively ) ; these beneficial effects were sustained throughout the 26-week study . QVA149 significantly improved dyspnoea and health status versus placebo ( p<0.001 and p = 0.002 , respectively ) and tiotropium ( p = 0.007 and p = 0.009 , respectively ) at week 26 . All treatments were well tolerated . Dual bronchodilation with once-daily QVA149 demonstrated superior and clinical ly meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator , with a safety and tolerability profile similar to placebo , supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting & bgr;2-agonist combinations for the treatment of COPD . Dual indacaterol/glycopyrronium therapy was safe and more efficacious than monotherapy in moderate-to-severe COPD Background The combination of the inhaled muscarinic antagonist umeclidinium ( UMEC ) with the long-acting β2-agonist vilanterol ( VI ) has been shown to provide significant improvements in lung function compared with UMEC , VI , or placebo ( PBO ) in patients with chronic obstructive pulmonary disease ( COPD ) . This study was specifically design ed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population . Methods This was a 12-week multicenter , r and omized , double-blind , parallel-group , placebo-controlled study . Eligible patients were r and omized 1:1 to receive once-daily UMEC/VI 62.5/25 μg ( via ELLIPTA ® dry powder inhaler ) or PBO for 12 weeks . The primary endpoint was St George ’s Respiratory Question naire ( SGRQ ) total score at day 84 . Secondary efficacy endpoints included rescue albuterol use ( puffs/day ) over weeks 1–12 and trough forced expiratory volume in 1 second on day 84 . Adverse events were also assessed . Results A total of 496 patients were included in the intent-to-treat population in the UMEC/VI ( n=248 ) and PBO ( n=248 ) treatment groups . UMEC/VI 62.5/25 μg provided a significant and clinical ly meaningful improvement in SGRQ total score at day 84 versus PBO ( difference between treatments in SGRQ total score change from baseline : −4.03 [ 95 % confidence interval { CI } : −6.28 , −1.79 ] ; P<0.001 ) . UMEC/VI 62.5/25 μg result ed in a statistically significant reduction in rescue albuterol use versus PBO ( −0.7 puffs/day [ 95 % CI : −1.1 , −0.4 ] ; P<0.001 ) . UMEC/VI 62.5/25 μg provided a significant and clinical ly meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO ( 122 mL [ 95 % CI : 71 , 172 ] ; P<0.001 ) . The incidence of adverse events was similar between treatments ( 32 % and 30 % of patients in the UMEC/VI 62.5/25 μg and PBO groups , respectively ) . Conclusion The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinical ly important improvements in SGRQ and rescue medication use  versus PBO in patients with moderate-to-very-severe COPD NVA237 ( glycopyrronium bromide ) is a once-daily long-acting muscarinic antagonist ( LAMA ) in development for chronic obstructive pulmonary disease ( COPD ) . The GLycopyrronium bromide in COPD airWays clinical Study 2 ( GLOW2 ) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks . Patients were r and omised 2:1:1 to NVA237 50 μg , placebo or open-label tiotropium 18 μg for 52 weeks . Primary end-point was trough forced expiratory volume in 1 s ( FEV1 ) at 12 weeks . 1,066 patients were r and omised , 810 completed the study . At week 12 , trough FEV1 increased significantly by 97 mL with NVA237 ( 95 % CI 64.6–130.2 ; p<0.001 ) and 83 mL with tiotropium ( 95 % CI 45.6–121.4 ; p<0.001 ) . Compared with placebo , NVA237 produced significant improvements in dyspnoea ( Transition Dyspnoea Index at week 26 ; p=0.002 ) and health status ( St George 's Respiratory Question naire at week 52 ; p<0.001 ) . NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34 % ( p=0.001 ) and the use of rescue medication ( p=0.039 ) , versus  placebo  . NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes . Safety profiles were similar across groups . NVA237 50 μg provided significant improvements in lung function , dyspnoea , health status , exacerbations and rescue medication use , versus placebo , and was comparable to tiotropium . NVA237 can potentially be an alternative choice of LAMA for COPD patients Background NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease ( COPD ) . The glycopyrronium bromide in COPD airways clinical study 1 ( GLOW1 ) evaluated the efficacy , safety and tolerability of NVA237 in patients with moderate-to-severe COPD . Methods Patients with COPD with a smoking history of ≥ 10 pack-years , post-bronchodilator forced expiratory volume in 1 second ( FEV1 ) < 80 % and ≥ 30 % predicted normal and FEV1/forced vital capacity < 0.70 were enrolled . Patients were r and omized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry . The primary outcome measure was trough FEV1 at Week 12 . Results A total of 822 patients were r and omized to NVA237 ( n = 552 ) or placebo ( n = 270 ) . Least squares mean ( ± st and ard error ) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 ( 1.408 ± 0.0105 L ) , versus placebo ( 1.301 ± 0.0137 L ; treatment difference 108 ± 14.8 mL , p < 0.001 ) . Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26 . FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26 , and at all other visits and timepoints . Transition dyspnoea index focal scores and St. George 's Respiratory Question naire scores were significantly improved with NVA237 versus placebo at Week 26 , with treatment differences of 1.04 ( p < 0.001 ) and -2.81 ( p = 0.004 ) , respectively  . NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31 % ( p = 0.023 ) and use of rescue medication by 0.46 puffs per day ( p = 0.005 ) , versus placebo . NVA237 was well tolerated and had an acceptable safety profile , with a low frequency of cardiac and typical antimuscarinic adverse effects . Conclusions Once-daily NVA237 was safe and well tolerated and provided rapid , sustained improvements in lung function , improvements in dyspnoea , and health-related quality of life , and reduced the risk of exacerbations and the use of rescue medication . Trial registration Clinical Trials.gov : BACKGROUND Fluticasone furoate/vilanterol ( FF/VI ) is an inhaled corticosteroid/long-acting beta2-agonist ( ICS/LABA ) , recently approved as once-daily maintenance therapy for COPD . We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol ( FP/SAL ) . METHODS Three 12 week studies comparing FF/VI and FP/SAL were conducted . Patients aged ≥40 years with moderate-to-very severe COPD were r and omized to receive double-blind , double-dummy FF/VI 100/25 mcg once-daily , or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period . The primary endpoint of each study was change from baseline trough in 0 - 24 h weighted mean FEV 
    Output:
    