INTREPID: Investigation of TRELEGY Effectiveness: Usual Practice Design

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

The Clinical Effectiveness of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in a Single Inhaler (TRELEGY™ ELLIPTA™) When Compared With Non-ELLIPTA Multiple Inhaler Triple Therapies in COPD Patients Within a Usual Care Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03467425
• Other study ID #: 206854
• Secondary ID: 2017-004369-29
• Status: Completed
• Phase: Phase 4
• Start date: April 11, 2018
• Est. completion date: October 10, 2019

Study information

• Verified date: July 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to assess the effectiveness of TRELEGY ELLIPTA relative to non-ELLIPTA Multiple Inhaler Triple Therapies (MITT) for Chronic Obstructive Pulmonary Disease (COPD) control within the usual clinical practice setting. The study will be conducted once TRELEGY ELLIPTA has been approved in the countries in which the study will be conducted and is available commercially. This is a randomized, open-label, effectiveness, phase 4 study of 24 weeks' duration in COPD subjects to evaluate TRELEGY ELLIPTA (fluticasone furoate [FF]/vilanterol [VI]/umeclidinium bromide [UMEC]: 100 microgram [mcg]/62.5 mcg/25 mcg) inhalation powder taken once daily using a single ELLIPTA inhaler compared with any non-ELLIPTA MITT in the usual care setting. Effectiveness of TRELEGY ELLIPTA will be assessed by comparing proportion of COPD Assessment Test (CAT) responders at Week 24 between two treatment groups. TRELEGY and ELLIPTA are trademarks of GlaxoSmithKline (GSK) group of companies. The study will enroll approximately 3000 subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3109
• Est. completion date: October 10, 2019
• Est. primary completion date: October 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Capable of giving signed informed consent.

• Subjects with a documented physician diagnosis of COPD.

• A score of >=10 on the CAT at screening.

• Subjects who have a history of treatment with systemic/oral corticosteroids, antibiotics and/or hospitalization for at least one COPD exacerbation in the 3 years prior to randomization. This will be captured through subject recall and/or medical records and must be documented in subject's notes. Prior use of systemic/oral corticosteroids and/or antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD.

• Subjects currently receiving one of the non-ELLIPTA maintenance therapies listed below who have been prescribed it continually for at least 16 weeks prior to randomization. Continuous prescription is defined as a minimum of 60 days' prescription cover during the prior 16 weeks. The non-ELLIPTA maintenance therapy must be one of the following: Inhaled Corticosteroid (ICS) in combination with Long-acting Muscarinic Receptor Antagonist (LAMA) and Long Acting Beta-Agonist (LABA) (MITT) or LAMA and LABA used in combination as a dual therapy or LABA and ICS used in combination as a dual therapy. Subjects who are currently on a dual maintenance therapy for COPD must be considered by their physician to require a step-up to triple therapy. The reason for the physician decision to step- up must be documented. Subjects who are receiving only COPD medication on an 'as required' basis are not eligible.

• Subjects must be aged >=40 years of age at the time of signing the informed consent.

Exclusion Criteria:

• Women of child bearing potential: Women who are pregnant or lactating or are planning on becoming pregnant during the study.

• Subjects with any life-threatening condition i.e. low probability, in the opinion of the investigator, of 6-month survival due to severity of COPD or comorbid condition.

• Subjects with resolution of an exacerbation less than 2 weeks prior to visit 1, must not be randomized. Subjects may be rescreened 2 weeks after resolution of exacerbation (exacerbation is defined by treatment with systemic corticosteroids and/or antibiotic).

• Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the effectiveness or safety analysis if the disease/condition exacerbated during the study.

• A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator contraindicates study participation.

• Subjects who, in the opinion of the treating investigator, are chronic users of oral corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening). Chronic use is defined as more than 14 days continuous use during the 12 weeks prior to visit 1.

• Subjects taking any investigational drug treatment within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study (whichever is the longer of the two).

Related Conditions & MeSH terms

• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• FF/UMEC/VI
FF is a dry white powder containing 100 mcg GW685698 blended with lactose in one blister in the first strip of the DPI. UMEC/VI is a dry white powder containing 62.5 mcg of UMEC and 25 mcg of VI per blister, both blended together with lactose and magnesium stearate in the second strip of the DPI.
• Inhaled Corticosteroid
Inhaled Corticosteroid (ICS) as prescribed by the physician.
• LAMA
LAMA as prescribed by the physician.
• LABA
LABA as prescribed by the physician.
• COPD rescue medications
Rescue medications for COPD will be prescribed and obtained according to usual practice.

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Bergisch Gladbach	Nordrhein-Westfalen
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Dachau	Bayern
Germany	GSK Investigational Site	Darmstadt	Hessen
Germany	GSK Investigational Site	Deggendorf
Germany	GSK Investigational Site	Delitzsch	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Fuerstenwalde	Brandenburg
Germany	GSK Investigational Site	Fulda	Hessen
Germany	GSK Investigational Site	Garmisch-Partenirchen	Bayern
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Marburg	Hessen
Germany	GSK Investigational Site	Peine	Niedersachsen
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Rheine	Nordrhein-Westfalen
Germany	GSK Investigational Site	Rodgau	Hessen
Germany	GSK Investigational Site	Ruedersdorf	Brandenburg
Germany	GSK Investigational Site	Ruesselsheim	Hessen
Germany	GSK Investigational Site	Schleswig	Schleswig-Holstein
Germany	GSK Investigational Site	Schmoelln	Thueringen
Germany	GSK Investigational Site	Teuchern	Sachsen-Anhalt
Germany	GSK Investigational Site	Wallerfing	Bayern
Germany	GSK Investigational Site	Wardenburg	Niedersachsen
Germany	GSK Investigational Site	Warendorf	Nordrhein-Westfalen
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Dordrecht
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Harderwijk
Netherlands	GSK Investigational Site	Heerlen
Netherlands	GSK Investigational Site	Hengelo
Netherlands	GSK Investigational Site	Hoorn
Netherlands	GSK Investigational Site	Kloosterhaar
Netherlands	GSK Investigational Site	Nijmegen
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Zeist
Netherlands	GSK Investigational Site	Zutphen
Spain	GSK Investigational Site	Alcorcón (Madrid)
Spain	GSK Investigational Site	Alzira/Valencia
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Basurto/Bilbao
Spain	GSK Investigational Site	Benalmádena, Málaga
Spain	GSK Investigational Site	Caceres
Spain	GSK Investigational Site	Cádiz
Spain	GSK Investigational Site	L'Hospitalet De Llobregat. Barcelona
Spain	GSK Investigational Site	La Roca Del Valles (Barcelona)
Spain	GSK Investigational Site	Laredo	Cantabria
Spain	GSK Investigational Site	Logroño
Spain	GSK Investigational Site	Loja/ Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Marbella - Málaga	Andalucia
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Ponferrada (León)
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Segovia
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Torrejón de Ardoz	Madrid
Spain	GSK Investigational Site	Vigo-Pontevedra
Spain	GSK Investigational Site	Zaragoza
Sweden	GSK Investigational Site	Angered
Sweden	GSK Investigational Site	Flen
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Härnösand
Sweden	GSK Investigational Site	Höllviken
Sweden	GSK Investigational Site	Kristianstad
Sweden	GSK Investigational Site	Kungsbacka
Sweden	GSK Investigational Site	Luleå
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Motala
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Östersund
Sweden	GSK Investigational Site	Södertälje
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Trollhättan
United Kingdom	GSK Investigational Site	Bebington
United Kingdom	GSK Investigational Site	Bexhill	Sussex East
United Kingdom	GSK Investigational Site	Bollington	Cheshire
United Kingdom	GSK Investigational Site	Buckley
United Kingdom	GSK Investigational Site	Cardiff
United Kingdom	GSK Investigational Site	Cardiff
United Kingdom	GSK Investigational Site	Colchester
United Kingdom	GSK Investigational Site	Corbridge
United Kingdom	GSK Investigational Site	Corby	Northamptonshire
United Kingdom	GSK Investigational Site	Cornwall
United Kingdom	GSK Investigational Site	Edinburgh
United Kingdom	GSK Investigational Site	Gateshead	Tyne & Wear
United Kingdom	GSK Investigational Site	Hull
United Kingdom	GSK Investigational Site	Irlam, Manchester
United Kingdom	GSK Investigational Site	Larbet
United Kingdom	GSK Investigational Site	Leiston	Suffolk
United Kingdom	GSK Investigational Site	Llanelli	Carmarthenshire
United Kingdom	GSK Investigational Site	Macclesfield	Cheshire
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Newport
United Kingdom	GSK Investigational Site	Newport, Isle Of Wight
United Kingdom	GSK Investigational Site	Poole
United Kingdom	GSK Investigational Site	Rhyl	Denbighshire
United Kingdom	GSK Investigational Site	Sandbach	Cheshire
United Kingdom	GSK Investigational Site	Soham	Cambridgeshire
United Kingdom	GSK Investigational Site	Southampton
United Kingdom	GSK Investigational Site	Swinton
United Kingdom	GSK Investigational Site	Warrington
United Kingdom	GSK Investigational Site	Waterlooville	Hampshire
United Kingdom	GSK Investigational Site	Wellingborough	Northamptonshire
United Kingdom	GSK Investigational Site	Wishaw	Lanarkshire

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Responders and Non-responders Based on the Chronic Obstructive Pulmonary Disease Assessment Test (CAT) at Week 24 and Number of Participants With Imputed CAT Score at Week 24	The CAT is a 8-item questionnaire, used to measure the health status of par. with COPD. Par. rated their experience on a 6-point scale: 0 (no impact) to 5 (maximum impact). CAT score was calculated by summing the non-missing scores of the 8 items with a range of 0-40. Higher scores indicate greater disease impact. Responders were par. who had a change from Baseline score >=2 at Week 24. Non-responders were the par. who had change from Baseline score <2 at Week 24. Change from Baseline was calculated as Week 24 value minus the Baseline value (Day 1). A composite strategy was applied when intercurrent events of randomized treatment modification, change in pulmonary rehabilitation or start of oxygen therapy occurred, otherwise a treatment policy strategy was applied. Missing Week 24 CAT data were imputed assuming missing at random and are presented in a separate category. Number of responders, non-responders based on CAT and par. with imputed CAT score at Week 24 are presented.	At Week 24
Secondary	Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the value recorded at Day 1. Change from Baseline was calculated as FEV1 value at Week 24 minus the Baseline value. A treatment policy strategy was used for the intercurrent events of randomized treatment discontinuation, randomized treatment modification, change of pulmonary rehabilitation status and start of oxygen therapy. Only those participants with non-missing covariates were included in the analysis.	Baseline (Day 1) and at Week 24
Secondary	Percentage of Participants Making at Least 1 Critical Error in Inhalation Technique at Week 24	Participants were trained on the correct use of their inhaler devices. All participants who had spirometry measured were to have an assessment of inhaler errors. During the assessment, participants were asked to demonstrate inhaler use when taking their regular dose of medication. A critical error is defined as an error that is most likely to result in no or significantly reduced medication being inhaled. These errors were recorded in an error checklist, during the assessment. A hypothetical strategy was used for the intercurrent event of randomized treatment modification. Percentage of participants making at least 1 critical error in inhalation technique at the Week 24 is presented.	At Week 24