SERETIDE 50/500mcg Versus Tiotropium Bromide On Exacerbation Rates In Severe Chronic Obstructive Pulmonary Disease

Multicentre, Randomised, Double-Blind, Double Dummy, Parallel Group, 104-week Study to Compare the Effect of the Salmeterol/Fluticasone Propionate Combination Product (SERETIDE*) 50/500mcg Delivered Twice Daily Via the DISKUS*/ACCUHALER* Inhaler With Tiotropium Bromide 18 mcg Delivered Once Daily Via the HandiHaler Inhalation Device on the Rate of Health Care Utilisation Exacerbations in Subjects With Severe Chronic Obstructive Pulmonary Disease (COPD)

This is a comparator study to assess the relative efficacy of the combination product fluticasone propionate/salmeterol 50/500 and tiotropium bromide on the rate of exacerbations of chronic obstructive pulmonary disease (COPD) over a two year study interval.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Tiotropium bromide 18mcg; Drug: Fluticasone propionate/ salmeterol combination 50/500mcg

Detailed Description

A Multicentre, Randomised, Double-Blind, Double Dummy, Parallel Group, 104 Week Study to Compare the Effect of the Salmeterol/Fluticasone Propionate Combination Product (SERETIDE) 50/500mcg with Tiotropium Bromide 18 mcg on the Rate of Exacerbations in Subjects with Severe Chronic Obstructive Pulmonary Disease (COPD)

• Study Type: Interventional
• Enrollment (Actual): 1270
• Phase: Phase 4

Contacts and Locations

Study Locations

• • • GSK Investigational Site
• Austria
  • Grimmenstein, Austria, A-2840
    • GSK Investigational Site
  • Moedling, Austria, A-2340
    • GSK Investigational Site
  • Salzburg, Austria, A-5020
    • GSK Investigational Site
  • Vienna, Austria, A-1120
    • GSK Investigational Site
• Belgium
  • Bruxelles, Belgium, 1000
    • GSK Investigational Site
  • Bruxelles, Belgium, 1020
    • GSK Investigational Site
  • Edegem, Belgium, 2650
    • GSK Investigational Site
  • Genk, Belgium, 3600
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site
• Czech Republic
  • Blansko, Czech Republic, 678 31
    • GSK Investigational Site
  • Kyjov, Czech Republic, 697 33
    • GSK Investigational Site
  • Olomouc, Czech Republic, 775 25
    • GSK Investigational Site
  • Ostrava, Czech Republic, 703 00
    • GSK Investigational Site
  • Plzen, Czech Republic, 301 00
    • GSK Investigational Site
  • Plzen, Czech Republic, 326 00
    • GSK Investigational Site
  • Praha 4, Czech Republic, 140 46
    • GSK Investigational Site
  • Praha 8, Czech Republic, 180 81
    • GSK Investigational Site
• Denmark
  • Aalborg, Denmark, DK-9100
    • GSK Investigational Site
  • Aarhus C, Denmark, DK-8000
    • GSK Investigational Site
  • Kobenhavn NV, Denmark, 2400
    • GSK Investigational Site
  • Odense C, Denmark, DK-5000
    • GSK Investigational Site
• Estonia
  • Paide, Estonia, 72712
    • GSK Investigational Site
  • Parnu, Estonia, 80024
    • GSK Investigational Site
  • Tallinn, Estonia, 13619
    • GSK Investigational Site
  • Tallinn, Estonia
    • GSK Investigational Site
  • Tallinn, Estonia, 1162
    • GSK Investigational Site
  • Tartu, Estonia, 51014
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10367
    • GSK Investigational Site
  • Berlin, Germany, 10178
    • GSK Investigational Site
  • Berlin, Germany, 10559
    • GSK Investigational Site
  • Berlin, Germany, 10965
    • GSK Investigational Site
  • Berlin, Germany, 10585
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Weinheim, Baden-Wuerttemberg, Germany, 69469
      • GSK Investigational Site
  • Bayern
    • Augsburg, Bayern, Germany, 86156
      • GSK Investigational Site
    • Bad Kissingen, Bayern, Germany, 97688
      • GSK Investigational Site
    • Bad Toelz, Bayern, Germany, 83646
      • GSK Investigational Site
    • Bad Woerrishofen, Bayern, Germany, 86825
      • GSK Investigational Site
    • Erlangen, Bayern, Germany, 91052
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81677
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80335
      • GSK Investigational Site
  • Hessen
    • Eschwege, Hessen, Germany, 37269
      • GSK Investigational Site
    • Gelnhausen, Hessen, Germany, 63571
      • GSK Investigational Site
    • Kassel, Hessen, Germany, 34121
      • GSK Investigational Site
    • Kassel, Hessen, Germany, 34117
      • GSK Investigational Site
    • Marburg, Hessen, Germany, 35037
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bielefeld, Nordrhein-Westfalen, Germany, 33602
      • GSK Investigational Site
• Greece
  • Athens, Greece, 15669
    • GSK Investigational Site
  • Athens, Greece, 184 54
    • GSK Investigational Site
  • Chania, Crete, Greece, 73300
    • GSK Investigational Site
  • Heraklion, Crete, Greece, 71409
    • GSK Investigational Site
  • Kavala, Greece
    • GSK Investigational Site
  • Periohi Dragana, Alexandroupolis, Greece, 68100
    • GSK Investigational Site
  • Rethymnon, Crete, Greece, 74100
    • GSK Investigational Site
• Italy
  • Campania
    • Eboli (SA), Campania, Italy, 84025
      • GSK Investigational Site
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
    • Salerno, Campania, Italy, 84126
      • GSK Investigational Site
    • Telese (BN), Campania, Italy, 82037
      • GSK Investigational Site
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44100
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • GSK Investigational Site
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20142
      • GSK Investigational Site
    • Rivolta d'Adda (CR), Lombardia, Italy, 26026
      • GSK Investigational Site
    • Sesto San Giovanni (MI), Lombardia, Italy, 20099
      • GSK Investigational Site
  • Marche
    • Ascoli Piceno, Marche, Italy, 63100
      • GSK Investigational Site
  • Puglia
    • Cassano Murge (BA), Puglia, Italy, 70020
      • GSK Investigational Site
    • Foggia, Puglia, Italy, 71100
      • GSK Investigational Site
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • GSK Investigational Site
  • Umbria
    • San Sisto (PG), Umbria, Italy, 06132
      • GSK Investigational Site
  • Veneto
    • Padova, Veneto, Italy, 35128
      • GSK Investigational Site
• Latvia
  • Jekabpils, Latvia, LV 5201
    • GSK Investigational Site
  • Riga, Latvia, LV 1002
    • GSK Investigational Site
  • Riga, Latvia, LV 1035
    • GSK Investigational Site
  • Riga, Latvia, LV1079
    • GSK Investigational Site
• Lithuania
  • Alytus, Lithuania, LT-62114
    • GSK Investigational Site
  • Kaunas, Lithuania, LT-50009
    • GSK Investigational Site
  • Klaipeda, Lithuania, LT-92288
    • GSK Investigational Site
  • Klaipeda, Lithuania, LT-92231
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-07156
    • GSK Investigational Site
• Netherlands
  • 's-HERTOGENBOSCH, Netherlands, 5211 NL
    • GSK Investigational Site
  • Almelo, Netherlands, 7609 PP
    • GSK Investigational Site
  • Almere, Netherlands, 1315 RA
    • GSK Investigational Site
  • Amersfoort, Netherlands, 3818 ES
    • GSK Investigational Site
  • Amsterdam, Netherlands, 1105 AZ
    • GSK Investigational Site
  • Amsterdam, Netherlands, 1091 AC
    • GSK Investigational Site
  • Amsterdam, Netherlands, 1034 CS
    • GSK Investigational Site
  • Arnhem, Netherlands, 6815 AD
    • GSK Investigational Site
  • Breda, Netherlands, 4819 EV
    • GSK Investigational Site
  • Eindhoven, Netherlands, 5623 EJ
    • GSK Investigational Site
  • Harderwijk, Netherlands, 3844 DG
    • GSK Investigational Site
  • Hoorn, Netherlands, 1624 NP
    • GSK Investigational Site
  • Leiderdorp, Netherlands, 2353 GA
    • GSK Investigational Site
  • Meppel, Netherlands, 7943 KA
    • GSK Investigational Site
  • OSS, Netherlands, 5342 BT
    • GSK Investigational Site
  • Sneek, Netherlands, 8601 ZK
    • GSK Investigational Site
  • Veldhoven, Netherlands, 5504 DB
    • GSK Investigational Site
  • Venlo, Netherlands, 5912 BL
    • GSK Investigational Site
  • Weert, Netherlands, 6001 BE
    • GSK Investigational Site
  • Zwolle, Netherlands, 8025 AB
    • GSK Investigational Site
• Norway
  • Bergen, Norway, 5053
    • GSK Investigational Site
  • Egsjordet, Norway
    • GSK Investigational Site
  • Fredrikstad, Norway, 1606
    • GSK Investigational Site
  • Gjettum, Norway, N-1346
    • GSK Investigational Site
  • Moelv, Norway, 2391
    • GSK Investigational Site
  • Oslo, Norway, 1150
    • GSK Investigational Site
  • Oslo, Norway, 855
    • GSK Investigational Site
  • Tonsberg, Norway, N-3117
    • GSK Investigational Site
  • Trondheim, Norway, N-7027
    • GSK Investigational Site
  • Trondheim, Norway, N-7030
    • GSK Investigational Site
  • Volda, Norway, 6100
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 050159
    • GSK Investigational Site
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Bucuresti, Romania, 70000
    • GSK Investigational Site
  • Cluj-Napoca, Romania, 400371
    • GSK Investigational Site
  • Deva, Romania, 2700
    • GSK Investigational Site
  • Iasi, Romania, 700115
    • GSK Investigational Site
• Russian Federation
  • Irkutsk, Russian Federation, 664005
    • GSK Investigational Site
  • Moscow, Russian Federation, 105 229
    • GSK Investigational Site
  • Moscow, Russian Federation, 105 077
    • GSK Investigational Site
  • Moscow, Russian Federation, 119 881
    • GSK Investigational Site
  • Moscow, Russian Federation, 109240
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197 089
    • GSK Investigational Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • GSK Investigational Site
  • Bratislava, Slovakia, 811 01
    • GSK Investigational Site
  • Bratislava, Slovakia, 833 40
    • GSK Investigational Site
  • Kosice, Slovakia, 040 01
    • GSK Investigational Site
  • Previdza, Slovakia, 971 01
    • GSK Investigational Site
• Slovenia
  • Golnik, Slovenia, 4204
    • GSK Investigational Site
  • Hoče, Slovenia, 2311
    • GSK Investigational Site
  • Litija, Slovenia, 1270
    • GSK Investigational Site
  • Topolšica, Slovenia, 3326
    • GSK Investigational Site
• Spain
  • Alicante, Spain
    • GSK Investigational Site
  • Barakaldo (Vizcaya), Spain, 48903
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08221
    • GSK Investigational Site
  • Figueres, Spain
    • GSK Investigational Site
  • Galdakano, Spain, 48960
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28047
    • GSK Investigational Site
  • Orihuela (Alicante), Spain
    • GSK Investigational Site
  • Vic, Spain, 28500
    • GSK Investigational Site
  • Zaragoza, Spain, 50009
    • GSK Investigational Site
• Sweden
  • Eksjö, Sweden, SE-575 81
    • GSK Investigational Site
  • Karlstad, Sweden, SE-651 85
    • GSK Investigational Site
  • Linköping, Sweden, SE-581 85
    • GSK Investigational Site
  • Luleå, Sweden, SE-971 89
    • GSK Investigational Site
  • Malmö, Sweden, SE-205 02
    • GSK Investigational Site
  • Stockholm, Sweden, SE-171 76
    • GSK Investigational Site
  • Stockholm, Sweden, SE-141 86
    • GSK Investigational Site
  • Uppsala, Sweden, SE-751 85
    • GSK Investigational Site
  • Örebro, Sweden, SE-701 85
    • GSK Investigational Site
• Ukraine
  • Kiev, Ukraine, 03680
    • GSK Investigational Site
  • Kiev, Ukraine, 3680
    • GSK Investigational Site
  • Kiev - 112, Ukraine
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, E2 9JX
    • GSK Investigational Site
  • Cambridgeshire
    • Peterborough, Cambridgeshire, United Kingdom, PE3 6DA
      • GSK Investigational Site
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G4 0SF
      • GSK Investigational Site
  • Lancashire
    • Liverpool, Lancashire, United Kingdom, L9 7AL
      • GSK Investigational Site
    • Manchester, Lancashire, United Kingdom, M8 5RB
      • GSK Investigational Site
  • Middlesex
    • Isleworth, Middlesex, United Kingdom, TW7 6AG
      • GSK Investigational Site
  • Midlothian
    • Edinburg, Midlothian, United Kingdom, EH3 9YW
      • GSK Investigational Site
  • Northumberland
    • Newcastle Upon Tyne, Northumberland, United Kingdom, NE7 7DN
      • GSK Investigational Site
    • Newcastle Upon Tyne, Northumberland, United Kingdom, NE1 4LP
      • GSK Investigational Site
  • Warwickshire
    • Birmingham, Warwickshire, United Kingdom, B15 2TH
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Established clinical history of moderate to severe COPD.
• Post bronchodilator FEV1 of < 50% of predicted normal.
• FEV1 / FVC ratio <70%.
• Reversibility to 400mcg albuterol of less or equal to 10 predicted at Visit 1.
• Free from exacerbation in the 6 weeks prior to screening.
• Current or former smoker with a smoking history of = 10 pack-years and has a history of COPD exacerbations.

Exclusion criteria:

• Current asthma, eczema, atopic dermatitis and/or allergic rhinitis.
• Has a known respiratory disorder other than COPD (e.g. lung cancer, sarcoidosis, tuberculosis or lung fibrosis).
• Has narrow-angle glaucoma, prostatic hyperplasia or obstruction of the neck of the bladder that in the opinion of the investigator should prevent the subject from entering the study.
• Has undergone lung transplantation and/or lung volume reduction.
• Female who is a nursing mother.
• Requires regular (daily) long-term oxygen therapy (LTOT).
• Is receiving beta-blockers (except eye drops).
• Has a serious, uncontrolled disease likely to interfere with the study.
• Has received any other investigational drugs within the 4 weeks prior to Visit 1.
• Has, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
• Has a known or suspected hypersensitivity to beta2-agonists, inhaled corticosteroids, anticholinergic agents or any components of the formulations (e.g. lactose or milk protein).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Rate of healthcare utilisation based exacerbations of COPD

Secondary Outcome Measures

Outcome Measure
Rates for exacerbations based on symptoms, treatment with oral corticosteroids and for antibioticsTime to next exacerbation, duration and difference between healthcare utilisation and symptom based exacerbation

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Calverley PMA, Stockley RA, Seemungal TAR, Hagan G, Willits LR, Riley JH, Wedzicha JA; Investigating New Standards for Prophylaxis in Reduction of Exacerbations (INSPIRE) Investigators. Reported pneumonia in patients with COPD: findings from the INSPIRE study. Chest. 2011 Mar;139(3):505-512. doi: 10.1378/chest.09-2992. Epub 2010 Jun 24.
• Chui D, Tejani AM. The INSPIRE trial results: are they truly breathtaking? Am J Respir Crit Care Med. 2009 Jan 1;179(1):80; author reply 80-1. doi: 10.1164/ajrccm.179.1.80. No abstract available.
• Hilleman DE, Malesker MA, Morrow LE, Schuller D. A systematic review of the cardiovascular risk of inhaled anticholinergics in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2009;4:253-63. doi: 10.2147/copd.s4620. Epub 2009 Jul 20.
• Lanes SF, Jara M. The INSPIRE study: influence of prior use and discontinuation of inhaled corticosteroids. Am J Respir Crit Care Med. 2008 Sep 1;178(5):543-4; author reply 544. doi: 10.1164/ajrccm.178.5.543. No abstract available.
• Middleton PG. Management of patients with COPD: a comparison of the INSPIRE and TORCH studies. Am J Respir Crit Care Med. 2008 Jul 1;178(1):106; author reply 106-7. doi: 10.1164/ajrccm.178.1.106. No abstract available.
• Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA; INSPIRE Investigators. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008 Jan 1;177(1):19-26. doi: 10.1164/rccm.200707-973OC. Epub 2007 Oct 4.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2003
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: August 7, 2006
• First Submitted That Met QC Criteria: August 7, 2006
• First Posted (Estimate): August 9, 2006

Study Record Updates

• Last Update Posted (Estimate): January 20, 2017
• Last Update Submitted That Met QC Criteria: January 19, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: tiotropium; SERETIDE; COPD exacerbation; fluticasone propionate/salmeterol combination
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Salmeterol Xinafoate; Tiotropium Bromide; Bromides
• Other Study ID Numbers: SCO40036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: SCO40036
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register