Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomised, Double-blind, Active-controlled Study to Evaluate the Impact of Stepwise Withdrawal of Inhaled Corticosteroid Treatment in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD) on Optimized Bronchodilator Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00975195
• Other study ID #: 352.2046
• Secondary ID: 2007-002522-29
• Status: Completed
• Phase: Phase 4
• First received: September 10, 2009
• Last updated: February 9, 2015
• Start date: February 2009
• Est. completion date: July 2013

Study information

• Verified date: February 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Dept of Health and Ageing Therapeutic Goods AdminBelgium: Federal Agency for Medicines and Health Products, FAMHPBrazil: National Health Surveillance AgencyBulgaria: Bulgarian Drug Agency, BG-1504 SofiaChina: Food and Drug AdministrationDenmark: The Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreat Britain: MHRAGreece: Ethics CommitteeHungary: National Institute of Pharmacy, H-1051 BudapestItaly: Ethics CommitteeNetherlands: Central Committee Research Involving Human SubjectsNew Zealand: Multicentre Ethics Committee/MedsafePhilippines: Bureau of Food and DrugsPoland: Registration Medicinal Product Medical Device Biocidal ProductRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSouth Africa: Medicines Control CouncilSpain: Spanish Agency of MedicinesTaiwan: Department of HealthTunisia: Office of Pharmacies and MedicinesTurkey: Ministry of Health Central Ethics CommitteeUkraine: Ministry of Health Care of Ukraine (MoH of Ukraine)
• Study type: Interventional

Clinical Trial Summary

This is a randomised study to be conducted in patients with severe to very severe Chronic Obstructive Pulmonary Disease (COPD) to establish whether there is a need for these patients to be continuously treated with an inhaled corticosteroid on top of two potent long-acting bronchodilators. The study also aims to identify the type of patients who are likely to benefit from inhaled corticosteroid maintenance therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2488
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion criteria:

1. Male or female aged 40 years or more

2. Severe to very severe chronic obstructive pulmonary disease (COPD)

3. Current or ex-smoker with smoking history of at least 10 pack years

4. At least one documented exacerbation of COPD in previous year

Exclusion criteria:

1. Significant diseases other than COPD; significant alcohol or drug abuse

2. Current clinical diagnosis of asthma requiring steroid treatment

3. History of thoracotomy with pulmonary resection

4. Regular use of daytime oxygen

5. Recent history (within 3 months) of myocardial infarction

6. Recent (within 6 weeks) respiratory infection or COPD exacerbation

7. Recent (within 6 weeks) treatment with systemic corticosteroids at doses in excess of 5milligram / day

8. Recent (within 3 months) unstable or life-threatening cardiac arrhythmia requiring intervention

9. Recent (within 1 year) hospitalisation for cardiac failure

10. Malignancy requiring chemotherapy or radiotherapy

11. Clinical diagnosis of bronchiectasis

12. Pregnant or nursing women

13. Known hypersensitivity to study drugs

14. Current or recent (within 30 days) participation in another clinical study

15. Current participation in or recent completion (within 4 weeks) of a pulmonary rehabilitation program

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• tiotropium inhalation

• salmeterol xinafoate

• fluticasone propionate

• placebo matched for fluticasone propionate

Locations

Country	Name	City	State
Australia	352.2046.61006 Boehringer Ingelheim Investigational Site	Concord	New South Wales
Australia	352.2046.61004 Boehringer Ingelheim Investigational Site	Daw Park	South Australia
Australia	352.2046.61001 Boehringer Ingelheim Investigational Site	Glebe	New South Wales
Australia	352.2046.61003 Boehringer Ingelheim Investigational Site	Toorak Gardens	South Australia
Australia	352.2046.61002 Boehringer Ingelheim Investigational Site	Westmead	New South Wales
Australia	352.2046.61005 Boehringer Ingelheim Investigational Site	Woodville	South Australia
Belgium	352.2046.32002 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	352.2046.32016 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	352.2046.32015 Boehringer Ingelheim Investigational Site	Eupen
Belgium	352.2046.32017 Boehringer Ingelheim Investigational Site	Gilly
Belgium	352.2046.32014 Boehringer Ingelheim Investigational Site	Herentals
Belgium	352.2046.32006 Boehringer Ingelheim Investigational Site	Jambes
Belgium	352.2046.32008 Boehringer Ingelheim Investigational Site	Lebbeke
Belgium	352.2046.32001 Boehringer Ingelheim Investigational Site	Leuven
Belgium	352.2046.32004 Boehringer Ingelheim Investigational Site	Middelheim
Belgium	352.2046.32010 Boehringer Ingelheim Investigational Site	Montigny-le-Tilleul
Belgium	352.2046.32013 Boehringer Ingelheim Investigational Site	Turnhout
Brazil	352.2046.55005 Boehringer Ingelheim Investigational Site	Goiania
Brazil	352.2046.55002 Boehringer Ingelheim Investigational Site	Goiânia
Brazil	352.2046.55001 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	352.2046.55006 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	352.2046.55003 Boehringer Ingelheim Investigational Site	Sao Paulo
Bulgaria	352.2046.35905 Boehringer Ingelheim Investigational Site	Bourgas
Bulgaria	352.2046.35902 Boehringer Ingelheim Investigational Site	Rousse
Bulgaria	352.2046.35904 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	352.2046.35906 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	352.2046.35907 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	352.2046.35908 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	352.2046.35903 Boehringer Ingelheim Investigational Site	Stara Zagora
Bulgaria	352.2046.35909 Boehringer Ingelheim Investigational Site	Veliko Tarnovo
China	352.2046.86002 Boehringer Ingelheim Investigational Site	Beijing
China	352.2046.86003 Boehringer Ingelheim Investigational Site	Beijing
China	352.2046.86006 Boehringer Ingelheim Investigational Site	Beijing
China	352.2046.86008 Boehringer Ingelheim Investigational Site	Chongqing
China	352.2046.86001 Boehringer Ingelheim Investigational Site	Guangzhou
China	352.2046.86004 Boehringer Ingelheim Investigational Site	Shanghai
China	352.2046.86005 Boehringer Ingelheim Investigational Site	Shanghai
China	352.2046.86007 Boehringer Ingelheim Investigational Site	Wuhan
Denmark	352.2046.45001 Boehringer Ingelheim Investigational Site	Aarhus C
Denmark	352.2046.45003 Boehringer Ingelheim Investigational Site	København NV
Denmark	352.2046.45002 Boehringer Ingelheim Investigational Site	Odense C
France	352.2046.3317A Boehringer Ingelheim Investigational Site	Brest
France	352.2046.3317B Boehringer Ingelheim Investigational Site	Brest
France	352.2046.3317C Boehringer Ingelheim Investigational Site	Brest
France	352.2046.3320A Boehringer Ingelheim Investigational Site	Castelnau le Lez
France	352.2046.3320B Boehringer Ingelheim Investigational Site	Castelnau le Lez
France	352.2046.3320C Boehringer Ingelheim Investigational Site	Castelnau le Lez
France	352.2046.3335A Boehringer Ingelheim Investigational Site	Clermont Ferrand cedex 1
France	352.2046.3314A Boehringer Ingelheim Investigational Site	Forbach
France	352.2046.3333A Boehringer Ingelheim Investigational Site	Marseille
France	352.2046.3301A Boehringer Ingelheim Investigational Site	Marseille cedex 20
France	352.2046.3326A Boehringer Ingelheim Investigational Site	Montpellier
France	352.2046.3326C Boehringer Ingelheim Investigational Site	Montpellier
France	352.2046.3334A Boehringer Ingelheim Investigational Site	Nantes
France	352.2046.3325A Boehringer Ingelheim Investigational Site	Nantes Cedex 1
France	352.2046.3325C Boehringer Ingelheim Investigational Site	Nantes Cedex 1
France	352.2046.3325D Boehringer Ingelheim Investigational Site	Nantes Cedex 1
France	352.2046.3324A Boehringer Ingelheim Investigational Site	Nîmes
France	352.2046.3332A Boehringer Ingelheim Investigational Site	Nîmes
France	352.2046.3332B Boehringer Ingelheim Investigational Site	Nîmes
France	352.2046.3332C Boehringer Ingelheim Investigational Site	Nîmes
France	352.2046.3331A Boehringer Ingelheim Investigational Site	Perpignan
France	352.2046.3331B Boehringer Ingelheim Investigational Site	Perpignan
France	352.2046.3331C Boehringer Ingelheim Investigational Site	Perpignan
France	352.2046.3329A Boehringer Ingelheim Investigational Site	Saint Laurent du Var
France	352.2046.3329B Boehringer Ingelheim Investigational Site	Saint Laurent du Var
France	352.2046.3302A Boehringer Ingelheim Investigational Site	Saint-Pierre cedex
France	352.2046.3302B Boehringer Ingelheim Investigational Site	Saint-Pierre cedex
France	352.2046.3302C Boehringer Ingelheim Investigational Site	Saint-Pierre cedex
France	352.2046.3302D Boehringer Ingelheim Investigational Site	Saint-Pierre cedex
France	352.2046.3337A Boehringer Ingelheim Investigational Site	Toulouse
France	352.2046.3336A Boehringer Ingelheim Investigational Site	Toulouse cedex 9
France	352.2046.3336B Boehringer Ingelheim Investigational Site	Toulouse cedex 9
France	352.2046.3336C Boehringer Ingelheim Investigational Site	Toulouse cedex 9
Germany	352.2046.49012 Boehringer Ingelheim Investigational Site	Berlin
Germany	352.2046.49020 Boehringer Ingelheim Investigational Site	Berlin
Germany	352.2046.49021 Boehringer Ingelheim Investigational Site	Berlin
Germany	352.2046.49008 Boehringer Ingelheim Investigational Site	Bochum
Germany	352.2046.49019 Boehringer Ingelheim Investigational Site	Cottbus
Germany	352.2046.49002 Boehringer Ingelheim Investigational Site	Donaustauf
Germany	352.2046.49013 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	352.2046.49025 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	352.2046.49023 Boehringer Ingelheim Investigational Site	Frankfurt/Main
Germany	352.2046.49024 Boehringer Ingelheim Investigational Site	Geesthacht
Germany	352.2046.49022 Boehringer Ingelheim Investigational Site	Gelnhausen
Germany	352.2046.49001 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	352.2046.49006 Boehringer Ingelheim Investigational Site	Heidelberg
Germany	352.2046.49014 Boehringer Ingelheim Investigational Site	Immenhausen
Germany	352.2046.49016 Boehringer Ingelheim Investigational Site	Kiel
Germany	352.2046.49003 Boehringer Ingelheim Investigational Site	Köln
Germany	352.2046.49004 Boehringer Ingelheim Investigational Site	Mainz
Germany	352.2046.49005 Boehringer Ingelheim Investigational Site	Marburg
Germany	352.2046.49015 Boehringer Ingelheim Investigational Site	München
Greece	352.2046.30003 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30004 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30005 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30007 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30008 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30011 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30012 Boehringer Ingelheim Investigational Site	Athens
Greece	352.2046.30006 Boehringer Ingelheim Investigational Site	Heraklion
Greece	352.2046.30009 Boehringer Ingelheim Investigational Site	Larisa
Greece	352.2046.30001 Boehringer Ingelheim Investigational Site	Thessaloniki
Greece	352.2046.30002 Boehringer Ingelheim Investigational Site	Thessaloniki
Hungary	352.2046.36003 Boehringer Ingelheim Investigational Site	Cegled
Hungary	352.2046.36002 Boehringer Ingelheim Investigational Site	Deszk
Hungary	352.2046.36004 Boehringer Ingelheim Investigational Site	Komarom
Hungary	352.2046.36006 Boehringer Ingelheim Investigational Site	Pecs
Hungary	352.2046.36001 Boehringer Ingelheim Investigational Site	Szarvas
Hungary	352.2046.36005 Boehringer Ingelheim Investigational Site	Szazhalombatta
Hungary	352.2046.36011 Boehringer Ingelheim Investigational Site	Szigetszentmiklos
Italy	352.2046.39002 Boehringer Ingelheim Investigational Site	Catania
Italy	352.2046.39007 Boehringer Ingelheim Investigational Site	Cona
Italy	352.2046.39005 Boehringer Ingelheim Investigational Site	Foggia
Italy	352.2046.39003 Boehringer Ingelheim Investigational Site	Modena
Italy	352.2046.39006 Boehringer Ingelheim Investigational Site	Montescano (pv)
Italy	352.2046.39001 Boehringer Ingelheim Investigational Site	Pisa
Italy	352.2046.39004 Boehringer Ingelheim Investigational Site	Sesto S. Giovanni (mi)
Italy	352.2046.39008 Boehringer Ingelheim Investigational Site	Tradate (va)
Netherlands	352.2046.31004 Boehringer Ingelheim Investigational Site	Heerlen
Netherlands	352.2046.31001 Boehringer Ingelheim Investigational Site	Leeuwarden
Netherlands	352.2046.31003 Boehringer Ingelheim Investigational Site	Rotterdam
Netherlands	352.2046.31002 Boehringer Ingelheim Investigational Site	Veldhoven
New Zealand	352.2046.64007 Boehringer Ingelheim Investigational Site	Auckland NZ
New Zealand	352.2046.64003 Boehringer Ingelheim Investigational Site	Christchurch
New Zealand	352.2046.64004 Boehringer Ingelheim Investigational Site	Dunedin
New Zealand	352.2046.64006 Boehringer Ingelheim Investigational Site	Hamilton
New Zealand	352.2046.64001 Boehringer Ingelheim Investigational Site	Newtown Wellington NZ
New Zealand	352.2046.64005 Boehringer Ingelheim Investigational Site	Otahuhu New Zealand
New Zealand	352.2046.64002 Boehringer Ingelheim Investigational Site	Tauranga
Philippines	352.2046.63001 Boehringer Ingelheim Investigational Site	Caloocan
Philippines	352.2046.63003 Boehringer Ingelheim Investigational Site	Manila
Philippines	352.2046.63004 Boehringer Ingelheim Investigational Site	Manila
Philippines	352.2046.63009 Boehringer Ingelheim Investigational Site	Muntinlupa
Philippines	352.2046.63005 Boehringer Ingelheim Investigational Site	Quezon
Philippines	352.2046.63007 Boehringer Ingelheim Investigational Site	Quezon
Philippines	352.2046.63006 Boehringer Ingelheim Investigational Site	Quezon City
Philippines	352.2046.63008 Boehringer Ingelheim Investigational Site	Quezon City
Poland	352.2046.48006 Boehringer Ingelheim Investigational Site	Bytom
Poland	352.2046.48003 Boehringer Ingelheim Investigational Site	Ostrow Wielkopolska
Poland	352.2046.48001 Boehringer Ingelheim Investigational Site	Poznan
Poland	352.2046.48002 Boehringer Ingelheim Investigational Site	Poznan
Poland	352.2046.48009 Boehringer Ingelheim Investigational Site	Rzeszow
Poland	352.2046.48011 Boehringer Ingelheim Investigational Site	Tarnowskie Gory
Poland	352.2046.48005 Boehringer Ingelheim Investigational Site	Warsaw
Poland	352.2046.48007 Boehringer Ingelheim Investigational Site	Wroclaw
Russian Federation	352.2046.07011 Boehringer Ingelheim Investigational Site	Ekaterinburg
Russian Federation	352.2046.07006 Boehringer Ingelheim Investigational Site	Ivanovo
Russian Federation	352.2046.07008 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	352.2046.07009 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	352.2046.07002 Boehringer Ingelheim Investigational Site	Samara
Russian Federation	352.2046.07003 Boehringer Ingelheim Investigational Site	Saratov
Russian Federation	352.2046.07001 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	352.2046.07004 Boehringer Ingelheim Investigational Site	Yaroslavl
Russian Federation	352.2046.07005 Boehringer Ingelheim Investigational Site	Yaroslavl
South Africa	352.2046.27006 Boehringer Ingelheim Investigational Site	Amanzimtoti
South Africa	352.2046.27002 Boehringer Ingelheim Investigational Site	Bellville
South Africa	352.2046.27001 Boehringer Ingelheim Investigational Site	Cape Town
South Africa	352.2046.27003 Boehringer Ingelheim Investigational Site	Cape Town
South Africa	352.2046.27007 Boehringer Ingelheim Investigational Site	Pretoria
South Africa	352.2046.27005 Boehringer Ingelheim Investigational Site	Somerset West
South Africa	352.2046.27004 Boehringer Ingelheim Investigational Site	Tygerberg
Spain	352.2046.34008 Boehringer Ingelheim Investigational Site	Badajoz
Spain	352.2046.34002 Boehringer Ingelheim Investigational Site	Barakaldo (Bilbao)
Spain	352.2046.34001 Boehringer Ingelheim Investigational Site	Barcelona
Spain	352.2046.34004 Boehringer Ingelheim Investigational Site	Barcelona
Spain	352.2046.34009 Boehringer Ingelheim Investigational Site	Hospitalet de Llobregat
Spain	352.2046.34006 Boehringer Ingelheim Investigational Site	Palma de Mallorca
Spain	352.2046.34010 Boehringer Ingelheim Investigational Site	Pozuelo de Alarcón
Spain	352.2046.34013 Boehringer Ingelheim Investigational Site	Salt (Girona)
Spain	352.2046.34011 Boehringer Ingelheim Investigational Site	Sevilla
Taiwan	352.2046.88606 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	352.2046.88604 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	352.2046.88601 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	352.2046.88603 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	352.2046.88607 Boehringer Ingelheim Investigational Site	Taiwan
Taiwan	352.2046.88608 Boehringer Ingelheim Investigational Site	Taiwan
Tunisia	352.2046.2161A Boehringer Ingelheim Investigational Site	Ariana
Tunisia	352.2046.2162A Boehringer Ingelheim Investigational Site	Ariana
Tunisia	352.2046.2165A Boehringer Ingelheim Investigational Site	Sfax
Tunisia	352.2046.2164A Boehringer Ingelheim Investigational Site	Sousse
Tunisia	352.2046.2163A Boehringer Ingelheim Investigational Site	Tunis
Turkey	352.2046.90009 Boehringer Ingelheim Investigational Site	Ankara
Turkey	352.2046.90019 Boehringer Ingelheim Investigational Site	Ankara
Turkey	352.2046.90016 Boehringer Ingelheim Investigational Site	Bursa
Turkey	352.2046.90010 Boehringer Ingelheim Investigational Site	Denizli
Turkey	352.2046.90003 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	352.2046.90004 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	352.2046.90006 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	352.2046.90008 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	352.2046.90012 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	352.2046.90017 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	352.2046.90011 Boehringer Ingelheim Investigational Site	Izmir
Turkey	352.2046.90014 Boehringer Ingelheim Investigational Site	Izmir
Turkey	352.2046.90018 Boehringer Ingelheim Investigational Site	Izmir
Turkey	352.2046.90005 Boehringer Ingelheim Investigational Site	Izmit
Turkey	352.2046.90007 Boehringer Ingelheim Investigational Site	Kayseri
Turkey	352.2046.90001 Boehringer Ingelheim Investigational Site	Mersin
Turkey	352.2046.90002 Boehringer Ingelheim Investigational Site	Samsun
Ukraine	352.2046.38007 Boehringer Ingelheim Investigational Site	Ivano-Frankivsk
Ukraine	352.2046.38002 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	352.2046.38003 Boehringer Ingelheim Investigational Site	Kharkov
Ukraine	352.2046.38004 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	352.2046.38006 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	352.2046.38005 Boehringer Ingelheim Investigational Site	Vinnitsa
Ukraine	352.2046.38001 Boehringer Ingelheim Investigational Site	Vinnytsya
United Kingdom	352.2046.44008 Boehringer Ingelheim Investigational Site	Baillieston, Glasgow
United Kingdom	352.2046.44009 Boehringer Ingelheim Investigational Site	Barnsley
United Kingdom	352.2046.44018 Boehringer Ingelheim Investigational Site	Belfast
United Kingdom	352.2046.44010 Boehringer Ingelheim Investigational Site	Birmingham
United Kingdom	352.2046.44003 Boehringer Ingelheim Investigational Site	Cambridge
United Kingdom	352.2046.44026 Boehringer Ingelheim Investigational Site	Chertsey
United Kingdom	352.2046.44006 Boehringer Ingelheim Investigational Site	Chesterfield
United Kingdom	352.2046.44012 Boehringer Ingelheim Investigational Site	Cottingham, Hull
United Kingdom	352.2046.44028 Boehringer Ingelheim Investigational Site	Inverness
United Kingdom	352.2046.44016 Boehringer Ingelheim Investigational Site	Isleworth
United Kingdom	352.2046.44002 Boehringer Ingelheim Investigational Site	Liverpool
United Kingdom	352.2046.44001 Boehringer Ingelheim Investigational Site	London
United Kingdom	352.2046.44017 Boehringer Ingelheim Investigational Site	Norwich
United Kingdom	352.2046.44021 Boehringer Ingelheim Investigational Site	Sheffield
United Kingdom	352.2046.44019 Boehringer Ingelheim Investigational Site	Sunderland
United Kingdom	352.2046.44025 Boehringer Ingelheim Investigational Site	Windsor

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Australia,  Belgium,  Brazil,  Bulgaria,  China,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  New Zealand,  Philippines,  Poland,  Russian Federation,  South Africa,  Spain,  Taiwan,  Tunisia,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Moderate or Severe On-treatment COPD Exacerbation	A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as an increase or new onset of =2 lower respiratory symptoms related to COPD, with =1 symptom lasting =3 days, requiring a change in treatment. Lower respiratory symptoms included shortness of breath, sputum production (volume), sputum purulence, cough, wheezing and chest tightness. A change in treatment included: hospitalisation/treatment in an urgent care unit, prescription of antibiotics and/or systemic steroids or a significant change of prescribed respiratory medication such as theophyllines, long-acting beta-agonists or inhaled corticosteroids. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for >6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.The "measure type" displays the 25th percentile and its 95% confidence interval.	During randomised treatment, up to 488 days	No
Secondary	Number of Moderate or Severe On-treatment COPD Exacerbations	Number of moderate or severe on-treatment COPD exacerbations, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was =7 days after the end date of the first exacerbation event were combined and counted as moderate or severe if =1 of the contributing exacerbation events was moderate or severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for >6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids.; Measured values show adjusted mean event rate.	During randomised treatment, up to 488 days	No
Secondary	Proportion of Patients With =1 Moderate or Severe On-treatment COPD Exacerbation	Presence (yes vs no) of at least one moderate or severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for >6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids.	During randomised treatment, up to 488 days	No
Secondary	Time to First Severe On-treatment COPD Exacerbation	Time to first severe on-treatment COPD exacerbation. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for >6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.; The "measure type" displays the 25th percentile and its 95% confidence interval.	During randomised treatment, up to 488 days	No
Secondary	Number of Severe On-treatment COPD Exacerbations	Number of severe on-treatment COPD exacerbations based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was =7 days after the end date of the first exacerbation event were combined and counted as severe if =1 of the contributing exacerbation events was severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for >6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.; Measured values show adjusted event rate.	During randomised treatment, up to 488 days	No
Secondary	Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation.	Presence (yes vs no) of at least one severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for >6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.	During randomised treatment, up to 488 days	No
Secondary	Time to First On-treatment COPD Exacerbation	Time to first on-treatment COPD exacerbation of any severity. The "measure type" displays the 25th percentile and its 95% confidence interval.	During randomised treatment, up to 488 days	No
Secondary	Number of On-treatment COPD Exacerbations	Number of on-treatment COPD exacerbations of any severity, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was =7 days after the end date of the first exacerbation event were combined.; Measured values show adjusted event rate.	During randomised treatment, up to 488 days	No
Secondary	Proportion of Patients With at Least One On-treatment COPD Exacerbation	Presence (yes vs no) of at least one on-treatment COPD exacerbation of any severity, displayed as a percentage.	During randomised treatment, up to 488 days	No
Secondary	Severity of On-treatment COPD Exacerbations	Severity of on-treatment COPD exacerbations: for each patient, the worst applicable category was taken (i.e. none, mild, moderate or severe)	During randomised treatment, up to 488 days	No
Secondary	Change in On-treatment Lung Function as Measured by Trough FEV1	Change from baseline in on-treatment lung function as measured by trough forced expiratory volume in one second (FEV1); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 6, 12, 18 and 52 visits	No
Secondary	Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale	Change from baseline in on-treatment dyspnoea as measured by the Modified Medical Research Council (MMRC) dyspnoea scale; change was calculated as week score minus baseline score. Negative changes from baseline indicate an improvement in health.; Scale from 0 to 4: 0 = not troubled by breathlessness, except during strenuous exercise; 1 = short of breath when hurrying or walking up a slight hill; 2 = walks slower than contemporaries on the same level because of breathlessness, or has to stop for breath when walking at own pace; 3 = stops for breath after approximately 100 yards, or after a few minutes on the level; 4 = too breathless to leave the house, or breathless when dressing or undressing; "No breathlessness" was given a score of -1; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 18 and 52 visits	No
Secondary	Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI)	Change from baseline in on-treatment physical health status as determined by body mass index (BMI); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 18 and 52 visits	No
Secondary	Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT)	Change from baseline in on-treatment exercise capacity measured by six-minute walk test (6-MWT); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 18 and 52 visits	No
Secondary	Change in On-treatment BODE Index	Change from baseline in on-treatment BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity index), a composite score ranging from 0 (best) to 10 (worst); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 18 and 52 visits	No
Secondary	Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "extremely/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to cough.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 12, 18 and 52 visits	No
Secondary	Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "a lot/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to cough.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 12, 18 and 52 visits	No
Secondary	Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "a lot/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to sputum.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 12, 18 and 52 visits	No
Secondary	Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain	Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from "not at all/never" to "extremely/always" on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to sputum.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 12, 18 and 52 visits	No
Secondary	Change in On-treatment FEV1 as Measured by Home Based Spirometry	Change from baseline in on-treatment Forced Expiratory Volume in One Second (FEV1) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if =4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits	No
Secondary	Change in On-treatment FVC as Measured by Home Based Spirometry	Change from baseline in on-treatment forced vital capacity (FVC) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if =4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits	No
Secondary	Change in On-treatment PEFR as Measured by Home Based Spirometry	Change from baseline in on-treatment peak expiratory flow rate (PEFR) as measured by home based spirometry; change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits	No
Secondary	Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Activity domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 27 and 52 visits	No
Secondary	Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Impact Domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 27 and 52 visits	No
Secondary	Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Symptoms domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 27 and 52 visits	No
Secondary	Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score	Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Total score. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 27 and 52 visits	No
Secondary	Change in On-treatment Physician Global Evaluation	Change from baseline in on-treatment physician global evaluation. The evaluation reflected the physician's opinion of the patient's overall condition and was based on the need for concomitant medication, the number and severity of exacerbations, the severity of cough, the ability to exercise, the amount of wheezing and any other relevant clinical observations. Patients were graded on a scale of 1 (poor) to 8 (excellent). Change was calculated as week score minus baseline score.; Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.	Baseline and week 27 and 52 visits	No

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