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Evaluation of the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD

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ClinicalTrials.gov Identifier: NCT02603393
Recruitment Status : Completed
First Posted : November 11, 2015
Results First Posted : April 29, 2019
Last Update Posted : April 29, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: QVA149
Drug: Tiotropium
Drug: Salmeterol/fluticasone
Enrollment 1053
Recruitment Details  
Pre-assignment Details  
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description 110/50 μg capsules o.d. for inhalation tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Period Title: Overall Study
Started 527 526
Completed 456 472
Not Completed 71 54
Reason Not Completed
Patient/guardian decision             32             18
Adverse Event             17             15
Technical problems             4             7
Lack of Efficacy             7             2
Death             3             4
Physician Decision             3             3
Protocol deviation             2             3
Lost to Follow-up             1             2
Non-compliance with study treatment             1             0
Sponsor decision             1             0
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone Total
Hide Arm/Group Description 110/50 μg capsules o.d. for inhalation tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.) Total of all reporting groups
Overall Number of Baseline Participants 527 526 1053
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 527 participants 526 participants 1053 participants
65.4  (7.99) 65.2  (7.62) 65.3  (7.80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 527 participants 526 participants 1053 participants
Female
149
  28.3%
161
  30.6%
310
  29.4%
Male
378
  71.7%
365
  69.4%
743
  70.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 527 participants 526 participants 1053 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
3
   0.6%
3
   0.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
526
  99.8%
523
  99.4%
1049
  99.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.2%
0
   0.0%
1
   0.1%
1.Primary Outcome
Title Mean Change From Baseline in Post-dose Trough FEV1
Hide Description Mean change from baseline in post-dose trough forced expiratory volume in 1 second (FEV1) following 26 weeks of treatment. Trough FEV1 is defined as the mean of the two FEV1 values measured at 23 hr 15 min and 23 hr 45 min after the morning dose taken at site on Day 181. Baseline FEV1 is defined as the average of the pre-dose FEV1 measured at -45 min and -15 min at Day 1.
Time Frame Baseline, 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.029  (0.0119) -0.003  (0.0115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority will be demonstrated if the 95% confidence interval of the treatment difference lies entirely to the right of (higher than) –50 mL.
Statistical Test of Hypothesis P-Value 0.0404
Comments 1 sided
Method Mixed Model for Repeated Measures Analys
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.026
Confidence Interval 95%
-0.053 to 0.001
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Annualized Rate of Moderate or Severe COPD Exacerbations
Hide Description Moderate or severe COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event.
Time Frame 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: COPD exacerbations/year
0.52
(0.43 to 0.63)
0.48
(0.40 to 0.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5802
Comments 2 sided
Method Generalized Linear Model Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of rates
Estimated Value 1.08
Confidence Interval 95%
0.83 to 1.40
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Annualized Rate of COPD Exacerbations Requiring Treatment With Systemic Glucocorticosteroids and/or Antibiotics, Moderate Exacerbations Only
Hide Description COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event
Time Frame 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: COPD Exacerbations/year
0.47
(0.39 to 0.58)
0.44
(0.36 to 0.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5651
Comments 2-sided
Method Generalized Linear Model Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of rates
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.82 to 1.43
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Annualized Rate of COPD Exacerbations Requiring Hospitalisation
Hide Description COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event.
Time Frame 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: COPD Exacerbations/year
0.001 [1] 
(0.0 to NA)
0.001 [1] 
(0.00 to NA)
[1]
NA - Not estimable No patient in either treatment group had an event
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9665
Comments 2-sided
Method Generalized Linear Model Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of rates
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.44 to 2.34
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in Pre-dose Trough FEV1
Hide Description Trough FEV1 is defined as the average of the pre-dose FEV1 measurements at -45 min and -15 min prior to dosing at each visit except Day 182 which is the average of the post-dose FEV1 measurements at 23h15min and 23h45min after dosing at Day 181. Baseline FEV1 is considered the Day 1 average of pre-dose measurements.
Time Frame 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.029  (0.0119) -0.003  (0.0115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0573
Comments 2-Sided
Method Mixed Model for Repeated Measures Analys
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.026
Confidence Interval 95%
-0.053 to 0.001
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline in St. George’s Respiratory Questionnaire
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is used to provide the health status measurements in this study. Baseline SGRQ-C is defined as the assessment taken right before the first dose of the double-blind drug on Day 1. Higher values correspond to greater impairment of health status. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-0.7  (0.53) -2.5  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments 2-Sided
Method Mixed Model for Repeated Measures Analys
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.8
Confidence Interval 95%
0.7 to 3.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline in St. George’s Respiratory Questionnaire
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is used to provide the health status measurements in this study. Baseline SGRQ-C is defined as the assessment taken right before the first dose of the double-blind drug on Day 1. Higher values correspond to greater impairment of health status. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
Time Frame Baseline, 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-1.0  (0.54) -2.5  (0.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0221
Comments 2-Sided
Method Mixed Model for Repeated measures Analys
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.2 to 2.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Transition Dyspnea Index (TDI) Score
Hide Description Transitional Dyspnea Index (TDI) score presents the degree of impairment due to dyspnea. The lower the score the worse the severity of dyspnea. The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
1.177  (0.1558) 1.418  (0.1508)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1724
Comments [Not Specified]
Method Mixed Model for Repeated Measures Analys
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.241
Confidence Interval 95%
-0.587 to 0.105
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Transition Dyspnea Index (TDI) Score
Hide Description Transitional Dyspnea Index (TDI) score presents the degree of impairment due to dyspnea. The lower the score the worse the severity of dyspnea. The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline.
Time Frame 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
1.382  (0.1567) 1.671  (0.1519)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1055
Comments 2-Sided
Method Mixed Model for Repated Measures Analysi
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.288
Confidence Interval 95%
-0.638 to 0.061
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication
Hide Description Change from baseline in mean daily number of puffs of rescue medication (number of puffs taken in the previous 12 hours) over 26 weeks of treatment.
Time Frame Baseline, 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Number of puffs per day
-0.307  (0.1006) -0.484  (0.0983)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0641
Comments 2-Sided
Method Linear Mixed Model Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.177
Confidence Interval 95%
-0.010 to 0.365
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Mean Change From Baseline in Forced Vital Capacity (FVC)
Hide Description Change from baseline in forced vital capacity following 26 weeks of treatment. Trough FVC is defined as the average of the pre-dose FVC measurements at -45 min and -15 min prior to dosing at each visit except Day 182 which is the average of the post-dose FVC measurements at 23h15min and 23h45min after dosing at Day 181. Baseline is considered the Day 1 average of pre-dose measurements.
Time Frame Baseline, 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug. Patients in the FAS were analyzed according to the treatment they were randomized to.
Arm/Group Title QVA149 Tiotropium + Salmeterol/Fluticasone
Hide Arm/Group Description:
110/50 μg capsules o.d. for inhalation
tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
Overall Number of Participants Analyzed 527 526
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.030  (0.0192) -0.048  (0.0186)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Tiotropium + Salmeterol/Fluticasone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4107
Comments 2-Sided
Method Mixed Model for Repeated Measures Analys
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.018
Confidence Interval (2-Sided) 95%
-0.025 to 0.061
Estimation Comments [Not Specified]
Time Frame The study consists of four epochs: screening (1 week), run-in (4 weeks), blinded treatment (26 weeks) and follow-up (4 weeks).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title QVA149 Tio+Salm/Flut
Hide Arm/Group Description 110/50 μg capsules o.d. for inhalation tiotropium (18 μg o.d.), and salmeterol/fluticasone propionate FDC (50/500 μg b.i.d.)
All-Cause Mortality
QVA149 Tio+Salm/Flut
Affected / at Risk (%) Affected / at Risk (%)
Total   4/527 (0.76%)   5/526 (0.95%) 
Show Serious Adverse Events Hide Serious Adverse Events
QVA149 Tio+Salm/Flut
Affected / at Risk (%) Affected / at Risk (%)
Total   32/527 (6.07%)   34/526 (6.46%) 
Blood and lymphatic system disorders     
Haemorrhagic anaemia † 1  0/527 (0.00%)  1/526 (0.19%) 
Cardiac disorders     
Acute myocardial infarction † 1  2/527 (0.38%)  0/526 (0.00%) 
Angina unstable † 1  1/527 (0.19%)  0/526 (0.00%) 
Atrial fibrillation † 1  1/527 (0.19%)  1/526 (0.19%) 
Cardiac arrest † 1  0/527 (0.00%)  1/526 (0.19%) 
Cardiac failure † 1  1/527 (0.19%)  0/526 (0.00%) 
Cardiac failure acute † 1  0/527 (0.00%)  1/526 (0.19%) 
Cardiac tamponade † 1  1/527 (0.19%)  0/526 (0.00%) 
Myocardial infarction † 1  2/527 (0.38%)  2/526 (0.38%) 
Myocardial ischaemia † 1  1/527 (0.19%)  0/526 (0.00%) 
Endocrine disorders     
Inappropriate antidiuretic hormone secretion † 1  1/527 (0.19%)  0/526 (0.00%) 
Gastrointestinal disorders     
Anal fissure † 1  0/527 (0.00%)  1/526 (0.19%) 
Duodenal ulcer † 1  0/527 (0.00%)  1/526 (0.19%) 
Haemorrhoids † 1  0/527 (0.00%)  1/526 (0.19%) 
Inguinal hernia † 1  1/527 (0.19%)  0/526 (0.00%) 
General disorders     
Non-cardiac chest pain † 1  1/527 (0.19%)  0/526 (0.00%) 
Pyrexia † 1  0/527 (0.00%)  1/526 (0.19%) 
Hepatobiliary disorders     
Cholelithiasis † 1  1/527 (0.19%)  0/526 (0.00%) 
Drug-induced liver injury † 1  1/527 (0.19%)  0/526 (0.00%) 
Infections and infestations     
Appendicitis † 1  1/527 (0.19%)  0/526 (0.00%) 
Lower respiratory tract infection † 1  0/527 (0.00%)  1/526 (0.19%) 
Ophthalmic herpes zoster † 1  0/527 (0.00%)  1/526 (0.19%) 
Pneumonia † 1  4/527 (0.76%)  3/526 (0.57%) 
Soft tissue infection † 1  1/527 (0.19%)  0/526 (0.00%) 
Upper respiratory tract infection † 1  1/527 (0.19%)  0/526 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture † 1  1/527 (0.19%)  0/526 (0.00%) 
Multiple injuries † 1  1/527 (0.19%)  0/526 (0.00%) 
Musculoskeletal and connective tissue disorders     
Systemic lupus erythematosus † 1  0/527 (0.00%)  1/526 (0.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder neoplasm † 1  0/527 (0.00%)  1/526 (0.19%) 
Cholesteatoma † 1  0/527 (0.00%)  1/526 (0.19%) 
Colon cancer † 1  1/527 (0.19%)  0/526 (0.00%) 
Colon neoplasm † 1  1/527 (0.19%)  0/526 (0.00%) 
Lung neoplasm † 1  0/527 (0.00%)  1/526 (0.19%) 
Lung neoplasm malignant † 1  0/527 (0.00%)  2/526 (0.38%) 
Metastases to central nervous system † 1  0/527 (0.00%)  1/526 (0.19%) 
Pituitary tumour benign † 1  1/527 (0.19%)  0/526 (0.00%) 
Prostate cancer † 1  0/527 (0.00%)  1/526 (0.19%) 
Renal neoplasm † 1  0/527 (0.00%)  1/526 (0.19%) 
Nervous system disorders     
Cerebral haemorrhage † 1  1/527 (0.19%)  0/526 (0.00%) 
Ischaemic stroke † 1  0/527 (0.00%)  1/526 (0.19%) 
Syncope † 1  0/527 (0.00%)  1/526 (0.19%) 
Renal and urinary disorders     
Renal failure † 1  1/527 (0.19%)  0/526 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure † 1  1/527 (0.19%)  0/526 (0.00%) 
Chronic obstructive pulmonary disease † 1  12/527 (2.28%)  13/526 (2.47%) 
Dyspnoea † 1  0/527 (0.00%)  1/526 (0.19%) 
Hypoxia † 1  1/527 (0.19%)  0/526 (0.00%) 
Pneumothorax † 1  0/527 (0.00%)  1/526 (0.19%) 
Pulmonary embolism † 1  0/527 (0.00%)  1/526 (0.19%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme † 1  1/527 (0.19%)  0/526 (0.00%) 
Vascular disorders     
Aortic aneurysm † 1  0/527 (0.00%)  1/526 (0.19%) 
Aortic aneurysm rupture † 1  0/527 (0.00%)  1/526 (0.19%) 
Aortic dissection † 1  0/527 (0.00%)  1/526 (0.19%) 
Deep vein thrombosis † 1  0/527 (0.00%)  1/526 (0.19%) 
Orthostatic hypotension † 1  1/527 (0.19%)  0/526 (0.00%) 
Peripheral arterial occlusive disease † 1  0/527 (0.00%)  1/526 (0.19%) 
Peripheral artery occlusion † 1  0/527 (0.00%)  1/526 (0.19%) 
Peripheral artery stenosis † 1  1/527 (0.19%)  0/526 (0.00%) 
1
Term from vocabulary, MedDRA (20.0)
†
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
QVA149 Tio+Salm/Flut
Affected / at Risk (%) Affected / at Risk (%)
Total   398/527 (75.52%)   392/526 (74.52%) 
Cardiac disorders     
Atrioventricular block first degree † 1  1/527 (0.19%)  6/526 (1.14%) 
Gastrointestinal disorders     
Diarrhoea † 1  3/527 (0.57%)  6/526 (1.14%) 
General disorders     
Non-cardiac chest pain † 1  3/527 (0.57%)  6/526 (1.14%) 
Oedema peripheral † 1  7/527 (1.33%)  3/526 (0.57%) 
Infections and infestations     
Bronchitis † 1  13/527 (2.47%)  5/526 (0.95%) 
Influenza † 1  6/527 (1.14%)  6/526 (1.14%) 
Oral candidiasis † 1  12/527 (2.28%)  18/526 (3.42%) 
Oropharyngeal candidiasis † 1  6/527 (1.14%)  7/526 (1.33%) 
Pneumonia † 1  2/527 (0.38%)  6/526 (1.14%) 
Respiratory tract infection viral † 1  1/527 (0.19%)  6/526 (1.14%) 
Upper respiratory tract infection bacterial † 1  2/527 (0.38%)  6/526 (1.14%) 
Urinary tract infection † 1  7/527 (1.33%)  1/526 (0.19%) 
Viral upper respiratory tract infection † 1  57/527 (10.82%)  59/526 (11.22%) 
Investigations     
Blood creatinine increased † 1  26/527 (4.93%)  24/526 (4.56%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  8/527 (1.52%)  9/526 (1.71%) 
Pain in extremity † 1  2/527 (0.38%)  6/526 (1.14%) 
Nervous system disorders     
Headache † 1  7/527 (1.33%)  13/526 (2.47%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease † 1  370/527 (70.21%)  353/526 (67.11%) 
Cough † 1  24/527 (4.55%)  15/526 (2.85%) 
Oropharyngeal pain † 1  7/527 (1.33%)  7/526 (1.33%) 
Vascular disorders     
Hypertension † 1  7/527 (1.33%)  10/526 (1.90%) 
1
Term from vocabulary, MedDRA (20.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
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Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02603393     History of Changes
Other Study ID Numbers: CQVA149A2316
2015-000114-22 ( EudraCT Number )
First Submitted: September 17, 2015
First Posted: November 11, 2015
Results First Submitted: July 9, 2018
Results First Posted: April 29, 2019
Last Update Posted: April 29, 2019