Trial Outcomes & Findings for INTREPID: Investigation of TRELEGY Effectiveness: Usual Practice Design (NCT NCT03467425)

Last Updated: 2020-09-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

3109 participants

Primary outcome timeframe

At Week 24

Results posted on

2020-09-07

Participant Flow

This was a Phase IV, open-label, randomized study to evaluate 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. TRELEGY and ELLIPTA are registered trademarks of GlaxoSmithKline group of companies.

A total of 3341 participants were screened and 3109 participants (Par.) were enrolled in this study. Of which, 3092 participants were randomized and received the study treatment. The remaining 17 participants were randomized in error (those who were recorded as screen failures and also randomized) and did not receive investigational product (IP).

Participant milestones

Participant milestones
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-ELLIPTA MITT Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.
Overall Study STARTED	1545	1547
Overall Study Randomized But Did Not Start IP	1	0
Overall Study Completed IP	1256	1359
Overall Study Not Completed IP	288	188
Overall Study Withdrew IP (WIP): Lost to Follow-up	15	24
Overall Study WIP: Protocol Deviation	0	2
Overall Study WIP: Adverse Event	112	29
Overall Study WIP: Lack of Efficacy	56	28
Overall Study WIP: Physician Decision	14	27
Overall Study WIP: Withdrawal by Participant	91	78
Overall Study COMPLETED	1498	1493
Overall Study NOT COMPLETED	47	54

Reasons for withdrawal

Reasons for withdrawal
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-ELLIPTA MITT Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.
Overall Study Adverse Event	9	9
Overall Study Lack of Efficacy	3	1
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	18	25
Overall Study Physician Decision	2	1
Overall Study Withdrawal by Subject	15	17

Baseline Characteristics

INTREPID: Investigation of TRELEGY Effectiveness: Usual Practice Design

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI n=1545 Participants Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-ELLIPTA MITT n=1547 Participants Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Total n=3092 Participants Total of all reporting groups
Age, Continuous	67.8 Years STANDARD_DEVIATION 8.78 • n=5 Participants	67.8 Years STANDARD_DEVIATION 8.59 • n=7 Participants	67.8 Years STANDARD_DEVIATION 8.68 • n=5 Participants
Sex: Female, Male Female	708 Participants n=5 Participants	729 Participants n=7 Participants	1437 Participants n=5 Participants
Sex: Female, Male Male	837 Participants n=5 Participants	818 Participants n=7 Participants	1655 Participants n=5 Participants
Race/Ethnicity, Customized Asian- Central/South Asian Heritage	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Asian- East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian- South East Asian Heritage	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White- Arabic/North African Heritage	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized White- White/Caucasian/European Heritage	1523 Participants n=5 Participants	1521 Participants n=7 Participants	3044 Participants n=5 Participants
Race/Ethnicity, Customized White and Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 24

Population: Intent-to-Treat (ITT) Population comprised of all randomized participants (any participant who received a randomization number), excluding those who were randomized in error (a screen failure and also randomized). Only those participants with non-missing covariates were included in the analysis

Outcome measures

Outcome measures
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI n=1539 Participants Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-ELLIPTA MITT n=1543 Participants Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.
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 Responders	731 Participants	616 Participants
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 Non-responders	756 Participants	835 Participants
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 Participants with imputed CAT score	52 Participants	92 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 24

Population: FEV1 Population comprised of all participants of the ITT population for whom a spirometry assessment was performed at any of Visit 1 (Day 1) or Visit 2 (Week 24). Only those participants with data available at the specified data points were analyzed.

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.

Outcome measures

Outcome measures
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI n=691 Participants Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-ELLIPTA MITT n=675 Participants Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 24	1.446 Liters Standard Error 0.0105	1.396 Liters Standard Error 0.0108

SECONDARY outcome

Timeframe: At Week 24

Population: Critical error Population comprised of all participants of the ITT population for whom a critical error assessment was performed at Visit 2 (Week 24). Only those participants with data available at the specified data points were analyzed.

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.

Outcome measures

Outcome measures
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI n=653 Participants Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-ELLIPTA MITT n=230 Participants Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.
Percentage of Participants Making at Least 1 Critical Error in Inhalation Technique at Week 24	6 Percentage of Participants	3 Percentage of Participants

Adverse Events

FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI

Serious events: 114 serious events

Other events: 32 other events

Deaths: 8 deaths

Non-Ellipta MITT

Serious events: 114 serious events

Other events: 3 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	FF /UMEC/VI: 100 mcg/62.5 mcg/25 mcg by ELLIPTA DPI n=1545 participants at risk Eligible participants received a combination of fluticasone furoate (FF) blended with lactose in the first strip (100 microgram \[mcg\] per blister); and umeclidinium bromide (UMEC) and vilanterol (VI) blended with lactose and magnesium stearate in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the same TRELEGY ELLIPTA dry powder inhaler (DPI) via inhalation route for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.	Non-Ellipta MITT n=1547 participants at risk Eligible participants received the inhaled corticosteroid (ICS)/long-acting muscarinic receptor antagonist (LAMA)/long-acting beta agonist (LABA) products twice daily as prescribed by the physician for a period of 24 weeks. Participants were administered other prescribed COPD medications such as rescue medications according to usual practice, as suggested by physician.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.1% 32/1545 • Number of events 32 • Serious adverse events (SAEs) and non-serious AEs (non-SAEs) were collected from the start of study treatment up to Week 24 Data is reported for the ITT Population which comprised of all randomized participants (who received a randomization number), excluding those who were randomized in error. All SAEs were collected. Non-SAEs which were only drug-related or that lead to withdrawal from study/study treatment were collected.	0.19% 3/1547 • Number of events 3 • Serious adverse events (SAEs) and non-serious AEs (non-SAEs) were collected from the start of study treatment up to Week 24 Data is reported for the ITT Population which comprised of all randomized participants (who received a randomization number), excluding those who were randomized in error. All SAEs were collected. Non-SAEs which were only drug-related or that lead to withdrawal from study/study treatment were collected.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER