Trial Outcomes & Findings for A Randomised Effectiveness Study Comparing Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) With Standard Treatment in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01551758)

Last Updated: 2017-05-31

Results Overview

Mean annual rate of moderate or severe COPD exacerbations during treatment were assessed. Moderate exacerbation: participant received exacerbation-related prescription of oral corticosteroids and/ or antibiotic (with/without National Health Service \[NHS\] contact) not requiring hospitalisation. Severe exacerbation: an exacerbation-related hospitalisation. Analysis method was Generalised Linear Model (GLM) assuming the negative binomial distribution with a log-link function and logarithm of time on treatment as an offset variable, adjusted for randomized treatment, baseline COPD maintenance therapy per randomisation stratification, number of moderate/severe COPD exacerbations in previous year and smoking status at baseline. Intent to treat (ITT) population: all randomised participants who received a prescription of study medication. Primary Efficacy Analysis Population: all ITT participants who had at least one moderate/severe exacerbation in the year prior to randomization

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2802 participants

Primary outcome timeframe

Up to 54 weeks

Results posted on

2017-05-31

Participant Flow

This was a multicentre, randomized, stratified, open-label study to evaluate the effectiveness and safety of fluticasone fuorate (FF)/vilanterol (VI) in participants followed in primary care who had a diagnosis of and received regular treatment for Chronic Obstructive Pulmonary Disease (COPD).

Participants (par.) were randomized 1:1 to receive 1 inhalation of FF/VI 100 microgram (mcg)/25 mcg once daily (QD) or continued their existing maintenance therapy for 12 months. 2802 par. were randomized (3 par. randomized to the FF/VI arm did not receive study medication). A total of 2799 par. comprised the Intent to Treat (ITT) Population.

Participant milestones

Participant milestones
Measure	Usual Care Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	Fluticasone Furoate (FF)/Vilanterol (VI) 100 mcg/25 mcg Participants were prescribed one inhalation of fluticasone furoate /vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Overall Study STARTED	1403	1396
Overall Study COMPLETED	1309	1291
Overall Study NOT COMPLETED	94	105

Reasons for withdrawal

Reasons for withdrawal
Measure	Usual Care Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	Fluticasone Furoate (FF)/Vilanterol (VI) 100 mcg/25 mcg Participants were prescribed one inhalation of fluticasone furoate /vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Overall Study Adverse Event	29	43
Overall Study Lack of Efficacy	0	1
Overall Study Protocol Violation	5	6
Overall Study Met Protocol-defined stopping criteria	8	10
Overall Study Lost to Follow-up	29	25
Overall Study Physician Decision	9	3
Overall Study Withdrawal by Subject	14	17

Baseline Characteristics

A Randomised Effectiveness Study Comparing Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) With Standard Treatment in Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.	Total n=2799 Participants Total of all reporting groups
Age, Continuous	66.7 Years STANDARD_DEVIATION 9.93 • n=5 Participants	66.6 Years STANDARD_DEVIATION 9.90 • n=7 Participants	66.7 Years STANDARD_DEVIATION 9.92 • n=5 Participants
Sex: Female, Male Female	671 Participants n=5 Participants	698 Participants n=7 Participants	1369 Participants n=5 Participants
Sex: Female, Male Male	732 Participants n=5 Participants	698 Participants n=7 Participants	1430 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Central/South Asian Heritage	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White-Arabic/North African Heritage	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	1387 Participants n=5 Participants	1376 Participants n=7 Participants	2763 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 54 weeks

Population: Primary Efficacy Analysis Population.

Outcome measures

Outcome measures
Measure	Usual Care n=1134 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1135 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Mean Annual Rate of Moderate or Severe COPD Exacerbations	1.90 Exacerbations per participant per year Interval 1.8 to 2.01	1.74 Exacerbations per participant per year Interval 1.65 to 1.84

SECONDARY outcome

Timeframe: Up to 58 weeks

Population: The Intent-to-Treat (ITT) Population: Defined as all participants who were randomised and received at least one prescription of study medication

Incidence of SAE of pneumonia was defined for each randomized treatment group as the proportion (number) of participants in that group who experienced at least one SAE of pneumonia in the Pneumonia Adverse Event of Special Interest subgroup during the treatment period (from start date of exposure to stop date of exposure + 28 days). Non-inferiority is demonstrated if the upper limit of the two-sided 95% confidence interval for the incidence ratio is less than 2. Serious Adverse Events of pneumonia are defined by the Pneumonia Special Interest Group, which for SAEs of pneumonia collected for these subjects includes the following preferred terms: Pneumonia, Pneumonia aspiration, Aspergillus infection, Empyema, Pneumonia streptococcal, Pneumonitis, Pulmonary tuberculosis.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of Participants With Serious Adverse Events (SAEs) of Pneumonia During the Study	83 Participants	94 Participants

SECONDARY outcome

Timeframe: Up to 58 weeks

Population: ITT Population.

The mean number of SAE of pneumonia over the treatment period (from first date of exposure to last date of exposure + 28 days was calculated. Analysis was performed using a negative binomial regression model with covariates of randomised treatment and with logarithm of time on treatment as an offset variable.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Mean Number of Serious Adverse Events of Pneumonia During the Study	0.07 Mean Number of SAE Interval 0.06 to 0.09	0.08 Mean Number of SAE Interval 0.06 to 0.09

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: ITT Population

The analysis method was a Cox proportional hazards model adjusted for randomized treatment. Analyses included those on-treatment SAEs of pneumonia that had an onset over the first 364 days of exposure, as defined. Participants who did not have an SAE of pneumonia during the first 364 days of the treatment period (start date of exposure to end date of exposure + 28 days were considered censored. Number of participants with event is presented.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Time to the First Serious Adverse Event of Pneumonia Occuring in a Year	80 Participants	89 Participants

SECONDARY outcome

Timeframe: Up to 54 weeks

Population: ITT Population.

A COPD-related secondary care contact was defined as an inpatient admission or a specialist outpatient visit or an accident \& emergency (A\&E) contact. A participant with an A\&E contact and subsequent inpatient admission was considered to have had two healthcare contacts. Inpatient admissions recorded at two hospitals on the same day, this was counted as a single (inpatient admission) secondary care contact. COPD-related contacts were identified using predefined lists of ICD-10 codes, specialty descriptions and diagnosis codes recorded in the patients electronic health record (EHR). GLM assuming the negative binomial distribution with log-link function and logarithm of time on treatment as an offset variable and adjusted for randomised treatment, baseline COPD maintenance therapy per randomisation stratification, number of moderate/severe COPD exacerbations in the previous year to randomisation and smoking status at baseline.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of COPD-related Secondary Care Contacts Expressed as Least Square Mean	1.48 Contacts per participant per year Interval 1.3 to 1.67	1.57 Contacts per participant per year Interval 1.39 to 1.78

SECONDARY outcome

Timeframe: Up to 54 weeks

Population: ITT Population.

A COPD-related primary care contact was defined as a primary care contact on a given calendar date with either a nurse, general physician (GP) or other healthcare professional that were considered as COPD-related, if the most prominent signs and symptoms the participant was presenting were as a direct result of the participant's COPD, as per Readcodes recorded in the patients electronic health record (EHR). The analysis method was General Linear Model assuming an underlying negative binomial distribution with a log-link function and logarithm of time on treatment as an offset variable and adjusted for randomised treatment, baseline COPD maintenance therapy per randomisation stratification, number of moderate/severe COPD exacerbations in the previous year to randomisation and smoking status at baseline.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of COPD-related Primary Care Contacts Expressed Using Least Square Mean	2.46 Contacts per participant per year Interval 2.34 to 2.58	2.42 Contacts per participant per year Interval 2.3 to 2.53

SECONDARY outcome

Timeframe: Up to 54 weeks

Population: ITT Population.

A secondary care contact was defined as an inpatient admission or a specialist outpatient visit or an A\&E contact. A participant with an A\&E contact and subsequent inpatient admission was considered to have had two healthcare contacts. In the situation where inpatient admissions were recorded at two hospitals on the same day, this was counted as a single secondary care contact. The analysis method was General Linear Model assuming an underlying negative binomial distribution with a log-link function and logarithm of time on treatment as an offset variable and adjusted for randomised treatment, baseline COPD maintenance therapy per randomization stratification, number of moderate/severe COPD exacerbations in the previous year to randomization and smoking status at baseline.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of All Secondary Care Contacts Expressed Using Least Square Mean	9.36 Contacts per participant per year Interval 8.74 to 10.02	9.81 Contacts per participant per year Interval 9.17 to 10.51

SECONDARY outcome

Timeframe: Up to 54 weeks

Population: ITT Population.

A primary care contact was defined as contact with a either a nurse, general practitioner, or other healthcare professional. The analysis method was General Linear Model assuming an underlying negative binomial distribution with a log-link function and logarithm of time on treatment as an offset variable and adjusted for randomised treatment, baseline COPD maintenance therapy per randomisation stratification, number of moderate/severe COPD exacerbations in the previous year to randomisation and smoking status at baseline.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of All Primary Care Contacts Expressed Using Least Square Mean	18.88 Contacts per participant per year Interval 18.06 to 19.74	21.20 Contacts per participant per year Interval 20.27 to 22.16

SECONDARY outcome

Timeframe: Up to 364 days

Population: ITT Population

Initial therapy was defined as the treatment that the subject was randomised to at randomisation. Discontinuation of initial therapy was defined as any modification of initial therapy. These included stepping up, stepping down or switching to another class/class combination, or withdrawal from the study. Switching within the same drug class did not count unless participant switched from FF/VI to a different ICS/LABA. The analysis method was a Cox proportional hazards model adjusted for randomized treatment. The probability of discontinuation of initial therapy was measured from the date of randomisation (i.e., exposure start date) to the date of discontinuation of initial therapy to which the participant was randomized, or date of treatment termination (Visit 6 or early withdrawal visit) for participants who completed the study without discontinuing the initial therapy (censored). Number of participants with event is presented.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Time to an Event of Discontinuation of Initial Therapy Occurring in a Year	219 Participants	374 Participants

SECONDARY outcome

Timeframe: Up to 364 days

Population: ITT Population

The date of an event for addition of a further COPD controller medication was defined as the exposure start date of the first modified treatment medication that included a new COPD maintenance therapy of a new class of drug (to the initial therapy) during the study treatment period, as collected on the investigational product page of the eCRF. Participants who did not add any COPD controller medication during the study were censored at the end of the treatment period (Day 364). This was equivalent to stepping up, defined as the addition of at least one new class of drug. The probability of an event was measured from the date of randomisation (i.e., treatment initiation) to the date of a change event. The analysis method was a Cox proportional hazards model adjusted for randomized treatment. Number of participants with event is presented.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Time to the Addition of a Further COPD Controller Medication Occurring in a Year	142 Participants	72 Participants

SECONDARY outcome

Timeframe: Up to 364 days

Population: ITT Population

The date of an event for moderate / severe COPD exacerbation was defined as the exacerbation onset date. The analysis method was a Cox proportional hazards model adjusted for randomized treatment. The probability of a first moderate / severe exacerbation was measured from the date of randomisation (i.e., treatment initiation) to the onset date of first moderate or severe COPD exacerbation, as recorded on eCRF, or date of treatment termination (Visit 6 or early withdrawal visit) for participants who completed the study without any moderate or severe exacerbations (censored). Participants who completed the study without a moderate or severe COPD exacerbation and analyses of time to first moderate/severe exacerbation were censored at Day 364. Number of participants with event is presented.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Time to First Moderate/Severe Exacerbations Occurring in a Year	977 Participants	947 Participants

SECONDARY outcome

Timeframe: Up to 364 days

Population: ITT Population

The date of an event for moderate / severe COPD exacerbation was defined as the exacerbation onset date. The analysis method was a Cox proportional hazards model adjusted for randomized treatment. The probability of first moderate / severe exacerbation on initial therapy was measured from the date of randomisation (i.e., exposure start date) to the onset date of first moderate or severe COPD exacerbation, or to the date of discontinuation of initial therapy (analysis was censored at date of discontinuation of initial therapy) for participants who completed the study without any moderate or severe exacerbations on initial therapy. Number of participants with event is presented.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Time to First Moderate/Severe Exacerbations on Initial Therapy Occurring in a Year	943 Participants	852 Participants

SECONDARY outcome

Timeframe: Up to 364 days

Population: ITT Population

The date of an event for severe exacerbation was defined as the exacerbation onset date. Participants who completed the study without a severe exacerbation were censored. The analysis method was a Cox proportional hazards model adjusted for randomized treatment. The probability of first severe exacerbation was measured from the date of randomisation (i.e., treatment initiation) to the onset date of first severe exacerbation, as recorded on eCRF, or date of treatment termination (Visit 6 or early withdrawal visit) for participants who completed the study without any severe exacerbations (censored). At Day 364, all participants who have not experienced a severe exacerbation are considered censored, regardless of whether their on-treatment phase continues beyond day 364, including those who withdrew early. Number of participants with event is presented.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Time to First Severe Exacerbations Occurring in a Year	97 Participants	122 Participants

SECONDARY outcome

Timeframe: Upto 58 weeks

Population: ITT Population

All SAEs included in the AE subgroup of special interest of "pneumonia" were considered as an SAE of pneumonias. A fatal SAE was defined as a SAE with outcome of fatal for study participant. The number of participants with fatal SAEs of pneumonia was assessed over 14 months.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of Participants With Fatal Serious Adverse Events of Pneumonia	13 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 54 weeks

Population: ITT Population

The number of participants with non-serious ADRs was assessed for up to 54 weeks. An ADR is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, for which there is a reasonable possibility that the untoward occurrence is causally related to the medicinal product. A non-serious ADR included one of the following: exacerbation of chronic or intermittent pre-existing condition; signs, symptoms, or the clinical sequelae of a suspected interaction; signs, symptoms, or new conditions detected or diagnosed after study treatment administration.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of Participants With Non-serious Adverse Drug Reactions (ADR)	88 Participants	192 Participants

SECONDARY outcome

Timeframe: Up to 56 weeks

Population: ITT Population

SAEs assessed included medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a significant medical event in the investigator's judgment, or is an event of possible drug-induced liver injury with hyperbilirubinaemia. SAEs were includes if the onset date was on or after the treatment start date and on or before the treatment stop date. However, the window for an SAE of pneumonia was longer and included 28 days post study treatment stop date.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of Participants With Serious Adverse Events	383 Participants	404 Participants

SECONDARY outcome

Timeframe: Upto 12 months

Population: ITT Population

A serious adverse drug reactions (SADR) is any untoward medical occurrence suspected to be medicinal product-related that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Usual Care n=1403 Participants Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 Participants Participants were prescribed one inhalation of fluticasone furoate/vilanterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Number of Participants With Serious Adverse Drug Reactions	10 Participants	23 Participants

Adverse Events

Usual Care

Serious events: 383 serious events

Other events: 40 other events

Deaths: 0 deaths

FF/VI 100 mcg/25 mcg

Serious events: 404 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Usual Care n=1403 participants at risk Participants continued their existing maintenance therapy that included one of the following: an inhaled corticosteroid (ICS) alone or Long Acting Beta Agonist (LABA) alone or Long Acting Muscarinic Antagonist (LAMA) alone or combination of any two (ICS+LABA/ ICS+LAMA/ LABA+LAMA) or triple therapy (ICS+LABA+LAMA) at the appropriate dosing schedule, for 12 months	FF/VI 100 mcg/25 mcg n=1396 participants at risk Participants were prescribed one inhalation of fluticasone fuorate /vilaneterol (FF/VI) 100 mcg/25 mcg via dry powder inhaler (DPI) once daily in the morning for 12 months in lieu of existing maintenance therapy. Participants on previous triple therapy received LAMA therapy additionally.
Infections and infestations Oral candidiasis	2.9% 40/1403 • Serious adverse events (SAEs; from Visit 1) and non-serious adverse drug reactions (from Visit 2) were collected from study medication start until the end of treatment (up to Visit 6 or withdrawal, ie, approximately 54 weeks)	4.0% 56/1396 • Serious adverse events (SAEs; from Visit 1) and non-serious adverse drug reactions (from Visit 2) were collected from study medication start until the end of treatment (up to Visit 6 or withdrawal, ie, approximately 54 weeks)

Additional Information

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Restriction type: OTHER