Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD

Effect of Inhalation of a Free Combination of Tiotropium Once Daily 18 Mcg and Salmeterol Twice Daily 50 Mcg Versus a Fixed Combination of Fluticasone and Salmeterol Twice Daily (500/50 Mcg) on Static Lung Volumes and Exercise Tolerance in COPD Patients (a Randomised, Double-blind, Double Dummy, 16 (2 x 8) Weeks, Crossover Study).

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00530842

Enrollment

344

Registered

2007-09-18

Start date

2007-09-30

Completion date

Unknown

Last updated

2013-12-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Brief summary

The primary objective of this study is to demonstrate that treatment with a free combination of tiotropium and salmeterol provides superior improvement in static lung volumes and exercise tolerance compared to a fixed combination of fluticasone and salmeterol in patients with COPD. The secondary objective includes assessment of safety.

Interventions

DRUGTiotropium plus Salmeterol

DRUGFluticasone/Salmeterol

Study design

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Eligibility

Sex/Gender

ALL

Age

40 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications. 2. The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD). 3. The patient has relatively stable, moderate to severe airway obstruction. 4. The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408): 1. Males Forced expiratory volume in the first second (FEV1) predicted \[Litres (L)\] = 4.30 x Height \[metres\] minus 0.029 x Age \[years\] minus 2.49 2. Females Forced expiratory volume in the first second (FEV1) predicted \[Litres (L)\] = 3.95 x Height \[metres\] minus 0.025 x Age \[years\] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month) 3. Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. \[Litres (L)\] = 2.34 x Height \[metres\] + 0.009 x Age \[years\] minus 1.09 4. Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. \[Litres (L)\] = 2.24 x Height \[metres\] + 0.001 x Age \[years\] minus 1.00 5. The patient is at least 40 years and less than or equal to 75 years old. 6. The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year. 7. The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol. 8. The patient is able to inhale the trial medication from the HandiHaler device. 9. The patient is able to inhale the trial medication from the Diskus/Accuhaler device.

Exclusion criteria

1. a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing), 2. a recent history of myocardial infarction within one year. 3. a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3. 4. daytime supplemental oxygen. 5. a diagnosis of known active tuberculosis. 6. a history of cancer within the last 5 years. 7. a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis. 8. thoracotomy with pulmonary resection. 9. an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD) 10. a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system. 11. a known symptomatic prostatic hypertrophy or bladder neck obstruction. 12. a known moderate or severe renal insufficiency. 13. a known narrow-angle glaucoma. 14. a known untreated hypokalemia. 15. a known untreated thyrotoxicosis. 16. a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3. 17. treatment with cromolyn sodium or nedocromil sodium 18. treatment with antihistamines or antileukotrienes. 19. treatment with tiotropium for 1 month before Visit 1. 20. treatment with oral corticosteroid medication. 21. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception 22. a history of or active alcohol or drug abuse. 23. an investigational drug within 1 month or 10 half lives 24. a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea. 25. participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD). 26. treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants. 27. participation in another study. 28. more than eight puffs of salbutamol/day during the run-in period

Design outcomes

Primary

Measure	Time frame	Description
Post-dose TGV(FRC) (After 8 Weeks)	8 weeks	Post-dose TGV(FRC) (Thoracic Gas Volume; co-primary endpoint) after 8 weeks
Endurance Time (After 8 Weeks)	8 weeks	Endurance time to the point of symptom limitation after 8 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)

Secondary

Measure	Time frame	Description
Static Lung Volumes	8 weeks	Trough TGV(FRC) (Thoracic Gas Volume) after 8 weeks (measured by bodyphlethysmography)
Static Lung Volumes (Percent)	8 weeks	Trough RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
Slow Vital Capacity (SVC)	8 weeks	Trough SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)
Forced Expiratory Volume in 1 Second (FEV1)	8 weeks	Trough FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)
Post-dose TGV(FRC) (After 4 Weeks)	4 weeks	Post-dose TGV(FRC) (Thoracic Gas Volume) after 4 weeks
FEV1 Over FVC (Percent)	8 weeks	Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)
Symptom Intensity During Exercise	8 weeks	Isotime Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10), 0 = no dyspnea, 10 = worst imaginable dyspnea
Dyspnea and Leg Discomfort	8 weeks	Peak Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10)
Locus of Symptom Limitation at Peak Exercise During Exercise	baseline	Reason for stopping exercise at baseline (leg discomfort, breathing discomfort, both or none)
Forced Vital Capacity (FVC)	8 weeks	Trough FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)
Endurance Time (After 4 Weeks)	4 weeks	Endurance time to the point of symptom limitation after 4 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)

Countries

Austria, Canada, France, Germany, Italy, Russia, Sweden

Participant flow

Recruitment details

All participant flow data are presented by treatment sequence

Participants by arm

Arm	Count
Tiotropium + Salmeterol / Fluticasone + Salmeterol Tio 18mcg o.d. + Sal 50mcg b.i.d. / Flu+Sal 500+50mcg b.i.d.	172
Fluticasone + Salmeterol / Tiotropium + Salmeterol Flu+Sal 500+50mcg b.i.d. / Tio 18mcg o.d. + Sal 50mcg b.i.d.	172
Total	344

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	10	6
Overall Study	Individual different reasons	4	3
Overall Study	Lack of Efficacy	2	1
Overall Study	Lost to Follow-up	0	4
Overall Study	Protocol Violation	3	2
Overall Study	Withdrawal by Subject	4	5
Period 1	Adverse Event	7	3
Period 1	Individual different reasons	2	3
Period 1	Lack of Efficacy	1	1
Period 1	Protocol Violation	2	1
Period 1	Withdrawal by Subject	2	3
Period 2	Adverse Event	3	3
Period 2	Individual different reasons	2	0
Period 2	Lack of Efficacy	1	0
Period 2	Lost to Follow-up	0	4
Period 2	Protocol Violation	1	0
Period 2	Withdrawal by Subject	1	2

Baseline characteristics

Characteristic	Tiotropium + Salmeterol / Fluticasone + Salmeterol	Fluticasone + Salmeterol / Tiotropium + Salmeterol	Total
Age, Continuous	61.5 Years STANDARD_DEVIATION 7.5	60.6 Years STANDARD_DEVIATION 7.6	61.0 Years STANDARD_DEVIATION 7.6
Sex: Female, Male Female	48 Participants	49 Participants	97 Participants
Sex: Female, Male Male	124 Participants	123 Participants	247 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	18 / 172	18 / 160	21 / 172	12 / 157
serious Total, serious adverse events	7 / 172	5 / 160	4 / 172	4 / 157

Outcome results

Primary

Endurance Time (After 8 Weeks)

Endurance time to the point of symptom limitation after 8 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEDIAN)	Dispersion
Tiotropium + Salmeterol	Endurance Time (After 8 Weeks)	463 Seconds	Inter-Quartile Range 375
Fluticasone + Salmeterol	Endurance Time (After 8 Weeks)	453 Seconds	Inter-Quartile Range 413

p-value: 0.340795% CI: [-9.5, 27.5]Wilcoxon signed-rank test

Primary

Post-dose TGV(FRC) (After 8 Weeks)

Post-dose TGV(FRC) (Thoracic Gas Volume; co-primary endpoint) after 8 weeks

Time frame: 8 weeks

Population: FAS using imputed values. The full analysis set (FAS) was defined to include all treated patients with any post-dosing efficacy data after at least 4 weeks for both investigational treatments in TGV(FRC) or endurance time.

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Post-dose TGV(FRC) (After 8 Weeks)	4.99 Litres	Standard Error 0.07
Fluticasone + Salmeterol	Post-dose TGV(FRC) (After 8 Weeks)	5.07 Litres	Standard Error 0.07

p-value: 0.048295% CI: [-0.174, -0.001]ANOVA

Secondary

Dyspnea and Leg Discomfort

Peak Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Dyspnea and Leg Discomfort	6.52 Unit on a Scale	Standard Deviation 2.36
Fluticasone + Salmeterol	Dyspnea and Leg Discomfort	6.61 Unit on a Scale	Standard Deviation 2.31

Secondary

Dyspnea and Leg Discomfort

Peak Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max 10)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Dyspnea and Leg Discomfort	6.10 Unit on a Scale	Standard Deviation 3.03
Fluticasone + Salmeterol	Dyspnea and Leg Discomfort	5.86 Unit on a Scale	Standard Deviation 3.01

Secondary

Endurance Time (After 4 Weeks)

Endurance time to the point of symptom limitation after 4 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEDIAN)	Dispersion
Tiotropium + Salmeterol	Endurance Time (After 4 Weeks)	458 Seconds	Inter-Quartile Range 331
Fluticasone + Salmeterol	Endurance Time (After 4 Weeks)	450 Seconds	Inter-Quartile Range 375

Secondary

FEV1 Over FVC (Percent)

Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	FEV1 Over FVC (Percent)	49.16 Percent of FEV1 over FVC	Standard Error 0.68
Fluticasone + Salmeterol	FEV1 Over FVC (Percent)	49.67 Percent of FEV1 over FVC	Standard Error 0.68

Secondary

FEV1 Over FVC (Percent)

Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	FEV1 Over FVC (Percent)	50.77 Percent of FEV1 over FVC	Standard Error 0.72
Fluticasone + Salmeterol	FEV1 Over FVC (Percent)	50.66 Percent of FEV1 over FVC	Standard Error 0.72

Secondary

FEV1 Over FVC (Percent)

Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	FEV1 Over FVC (Percent)	50.90 Percent of FEV1 over FVC	Standard Error 0.73
Fluticasone + Salmeterol	FEV1 Over FVC (Percent)	50.91 Percent of FEV1 over FVC	Standard Error 0.73

Secondary

FEV1 Over FVC (Percent)

Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	FEV1 Over FVC (Percent)	49.74 Percent of FEV1 over FVC	Standard Error 0.82
Fluticasone + Salmeterol	FEV1 Over FVC (Percent)	50.62 Percent of FEV1 over FVC	Standard Error 0.82

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	54.96 Percent of predicted FEV1	Standard Error 0.82
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	52.64 Percent of predicted FEV1	Standard Error 0.82

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	50.40 Percent of predicted FEV1	Standard Error 0.79
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	49.26 Percent of predicted FEV1	Standard Error 0.79

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.62 Litres	Standard Error 0.03
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.55 Litres	Standard Error 0.03

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Trough FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.48 Litres	Standard Error 0.03
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.45 Litres	Standard Error 0.03

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Trough FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.48 Litres	Standard Error 0.03
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.44 Litres	Standard Error 0.03

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.62 Litres	Standard Error 0.03
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	1.55 Litres	Standard Error 0.03

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	50.27 Percent of predicted FEV1	Standard Error 0.78
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	49.12 Percent of predicted FEV1	Standard Error 0.78

Secondary

Forced Expiratory Volume in 1 Second (FEV1)

Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	54.99 Percent of predicted FEV1	Standard Error 0.82
Fluticasone + Salmeterol	Forced Expiratory Volume in 1 Second (FEV1)	52.59 Percent of predicted FEV1	Standard Error 0.82

Secondary

Forced Vital Capacity (FVC)

Post-dose FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Vital Capacity (FVC)	3.26 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Forced Vital Capacity (FVC)	3.11 Litres	Standard Error 0.05

Secondary

Forced Vital Capacity (FVC)

Trough FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Vital Capacity (FVC)	3.04 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Forced Vital Capacity (FVC)	2.93 Litres	Standard Error 0.05

Secondary

Forced Vital Capacity (FVC)

Trough FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Vital Capacity (FVC)	3.06 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Forced Vital Capacity (FVC)	2.94 Litres	Standard Error 0.05

Secondary

Forced Vital Capacity (FVC)

Post-dose FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Forced Vital Capacity (FVC)	3.25 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Forced Vital Capacity (FVC)	3.11 Litres	Standard Error 0.05

Secondary

Locus of Symptom Limitation at Peak Exercise During Exercise

Reason for stopping exercise at baseline (leg discomfort, breathing discomfort, both or none)

Time frame: baseline

Population: FAS using imputed values

Arm	Measure	Group	Value (NUMBER)
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Leg discomfort	53 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Breathing discomfort	132 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Both (leg and breathing discomfort)	92 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	None	32 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	None	32 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Leg discomfort	53 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Both (leg and breathing discomfort)	92 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Breathing discomfort	132 Participants

Secondary

Locus of Symptom Limitation at Peak Exercise During Exercise

Reason for stopping exercise after 4 weeks (leg discomfort, breathing discomfort, both or none)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Group	Value (NUMBER)
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Leg discomfort	89 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Breathing discomfort	104 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Both (leg and breathing discomfort)	78 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	None	38 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	None	40 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Leg discomfort	72 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Both (leg and breathing discomfort)	78 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Breathing discomfort	119 Participants

Secondary

Locus of Symptom Limitation at Peak Exercise During Exercise

Reason for stopping exercise after 8 weeks (leg discomfort, breathing discomfort, both or none)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Group	Value (NUMBER)
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Leg discomfort	88 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Breathing discomfort	112 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Both (leg and breathing discomfort)	82 Participants
Tiotropium + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	None	27 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	None	28 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Leg discomfort	72 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Both (leg and breathing discomfort)	78 Participants
Fluticasone + Salmeterol	Locus of Symptom Limitation at Peak Exercise During Exercise	Breathing discomfort	131 Participants

Secondary

Post-dose TGV(FRC) (After 4 Weeks)

Post-dose TGV(FRC) (Thoracic Gas Volume) after 4 weeks

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Post-dose TGV(FRC) (After 4 Weeks)	5.00 Litres	Standard Error 0.07
Fluticasone + Salmeterol	Post-dose TGV(FRC) (After 4 Weeks)	5.19 Litres	Standard Error 0.07

Secondary

Slow Vital Capacity (SVC)

Post-dose SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Slow Vital Capacity (SVC)	3.39 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Slow Vital Capacity (SVC)	3.27 Litres	Standard Error 0.05

Secondary

Slow Vital Capacity (SVC)

Trough SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Slow Vital Capacity (SVC)	3.22 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Slow Vital Capacity (SVC)	3.12 Litres	Standard Error 0.05

Secondary

Slow Vital Capacity (SVC)

Trough SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Slow Vital Capacity (SVC)	3.19 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Slow Vital Capacity (SVC)	3.12 Litres	Standard Error 0.05

Secondary

Slow Vital Capacity (SVC)

Post-dose SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Slow Vital Capacity (SVC)	3.42 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Slow Vital Capacity (SVC)	3.28 Litres	Standard Error 0.05

Secondary

Static Lung Volumes

Trough RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	4.28 Litres	Standard Error 0.08
Fluticasone + Salmeterol	Static Lung Volumes	4.35 Litres	Standard Error 0.08

Secondary

Static Lung Volumes

Trough RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	4.23 Litres	Standard Error 0.08
Fluticasone + Salmeterol	Static Lung Volumes	4.25 Litres	Standard Error 0.08

Secondary

Static Lung Volumes

Trough TGV(FRC) (Thoracic Gas Volume) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	5.32 Litres	Standard Error 0.08
Fluticasone + Salmeterol	Static Lung Volumes	5.34 Litres	Standard Error 0.08

Secondary

Static Lung Volumes

Trough TGV(FRC) (Thoracic Gas Volume) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	5.24 Litres	Standard Error 0.08
Fluticasone + Salmeterol	Static Lung Volumes	5.25 Litres	Standard Error 0.08

Secondary

Static Lung Volumes

Post-dose IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	1.62 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	1.55 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Post-dose TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	7.33 Litres	Standard Error 0.09
Fluticasone + Salmeterol	Static Lung Volumes	7.47 Litres	Standard Error 0.09

Secondary

Static Lung Volumes

Post-dose IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	1.62 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	1.55 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Trough TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	7.47 Litres	Standard Error 0.09
Fluticasone + Salmeterol	Static Lung Volumes	7.39 Litres	Standard Error 0.09

Secondary

Static Lung Volumes

Trough TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	7.52 Litres	Standard Error 0.09
Fluticasone + Salmeterol	Static Lung Volumes	7.51 Litres	Standard Error 0.09

Secondary

Static Lung Volumes

Trough IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	1.47 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	1.42 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Trough IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	1.48 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	1.41 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Post-dose IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	2.46 Litres	Standard Error 0.05
Fluticasone + Salmeterol	Static Lung Volumes	2.37 Litres	Standard Error 0.05

Secondary

Static Lung Volumes

Post-dose IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	2.47 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	2.35 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Trough IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	2.28 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	2.23 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Trough IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	2.33 Litres	Standard Error 0.04
Fluticasone + Salmeterol	Static Lung Volumes	2.23 Litres	Standard Error 0.04

Secondary

Static Lung Volumes

Post-dose TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	7.36 Litres	Standard Error 0.09
Fluticasone + Salmeterol	Static Lung Volumes	7.36 Litres	Standard Error 0.09

Secondary

Static Lung Volumes

Post-dose RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	3.91 Litres	Standard Error 0.07
Fluticasone + Salmeterol	Static Lung Volumes	4.14 Litres	Standard Error 0.07

Secondary

Static Lung Volumes

Post-dose RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes	3.92 Litres	Standard Error 0.07
Fluticasone + Salmeterol	Static Lung Volumes	4.07 Litres	Standard Error 0.07

Secondary

Static Lung Volumes (Percent)

Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	70.59 Percent of TGV over TLC	Standard Error 0.47
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	70.99 Percent of TGV over TLC	Standard Error 0.47

Secondary

Static Lung Volumes (Percent)

Trough RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	56.10 Percent of RV over TLC	Standard Error 0.54
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	57.18 Percent of RV over TLC	Standard Error 0.54

Secondary

Static Lung Volumes (Percent)

Trough RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	56.57 Percent of RV over TLC	Standard Error 0.56
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	57.47 Percent of RV over TLC	Standard Error 0.56

Secondary

Static Lung Volumes (Percent)

Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	52.79 Percent of RV over TLC	Standard Error 0.54
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	55.02 Percent of RV over TLC	Standard Error 0.54

Secondary

Static Lung Volumes (Percent)

Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	53.09 Percent of RV over TLC	Standard Error 0.57
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	55.07 Percent of RV over TLC	Standard Error 0.57

Secondary

Static Lung Volumes (Percent)

Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	69.87 Percent of TGV over TLC	Standard Error 0.47
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	70.94 Percent of TGV over TLC	Standard Error 0.47

Secondary

Static Lung Volumes (Percent)

Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	68.43 Percent of TGV over TLC	Standard Error 0.49
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	69.22 Percent of TGV over TLC	Standard Error 0.49

Secondary

Static Lung Volumes (Percent)

Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Static Lung Volumes (Percent)	67.65 Percent of TGV over TLC	Standard Error 0.49
Fluticasone + Salmeterol	Static Lung Volumes (Percent)	68.85 Percent of TGV over TLC	Standard Error 0.49

Secondary

Symptom Intensity During Exercise

Isotime Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10), 0 = no dyspnea, 10 = worst imaginable dyspnea

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Symptom Intensity During Exercise	4.77 Unit on a Scale	Standard Error 0.13
Fluticasone + Salmeterol	Symptom Intensity During Exercise	4.98 Unit on a Scale	Standard Error 0.13

Secondary

Symptom Intensity During Exercise

Isotime Borg dyspnea scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no dyspnea, 10 = worst imaginable dyspnea

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Symptom Intensity During Exercise	4.80 Unit on a Scale	Standard Error 0.13
Fluticasone + Salmeterol	Symptom Intensity During Exercise	5.02 Unit on a Scale	Standard Error 0.13

Secondary

Symptom Intensity During Exercise

Isotime Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort

Time frame: 8 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Symptom Intensity During Exercise	4.64 Unit on a Scale	Standard Error 0.15
Fluticasone + Salmeterol	Symptom Intensity During Exercise	4.53 Unit on a Scale	Standard Error 0.15

Secondary

Symptom Intensity During Exercise

Isotime Borg leg discomfort scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort

Time frame: 4 weeks

Population: FAS using imputed values

Arm	Measure	Value (MEAN)	Dispersion
Tiotropium + Salmeterol	Symptom Intensity During Exercise	4.63 Unit on a Scale	Standard Error 0.15
Fluticasone + Salmeterol	Symptom Intensity During Exercise	4.63 Unit on a Scale	Standard Error 0.15

Source: ClinicalTrials.gov · Data processed: Mar 26, 2026

Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Endurance Time (After 8 Weeks)

Post-dose TGV(FRC) (After 8 Weeks)

Dyspnea and Leg Discomfort

Dyspnea and Leg Discomfort

Endurance Time (After 4 Weeks)

FEV1 Over FVC (Percent)

FEV1 Over FVC (Percent)

FEV1 Over FVC (Percent)

FEV1 Over FVC (Percent)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Expiratory Volume in 1 Second (FEV1)

Forced Vital Capacity (FVC)

Forced Vital Capacity (FVC)

Forced Vital Capacity (FVC)

Forced Vital Capacity (FVC)

Locus of Symptom Limitation at Peak Exercise During Exercise

Locus of Symptom Limitation at Peak Exercise During Exercise

Locus of Symptom Limitation at Peak Exercise During Exercise

Post-dose TGV(FRC) (After 4 Weeks)

Slow Vital Capacity (SVC)

Slow Vital Capacity (SVC)

Slow Vital Capacity (SVC)

Slow Vital Capacity (SVC)

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Static Lung Volumes (Percent)

Symptom Intensity During Exercise

Symptom Intensity During Exercise

Symptom Intensity During Exercise

Symptom Intensity During Exercise