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

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ClinicalTrials.gov Identifier: NCT01551758
Recruitment Status : Completed
First Posted : March 13, 2012
Results First Posted : March 7, 2017
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: FF/VI
Other: Existing Maintenance Therapy
Enrollment 2802
Recruitment Details 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).
Pre-assignment Details 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.
Arm/Group Title Usual Care Fluticasone Furoate (FF)/Vilanterol (VI) 100 mcg/25 mcg
Hide Arm/Group Description 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 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.
Period Title: Overall Study
Started 1403 1396
Completed 1309 1291
Not Completed 94 105
Reason Not Completed
Adverse Event             29             43
Lack of Efficacy             0             1
Protocol Violation             5             6
Met Protocol-defined stopping criteria             8             10
Lost to Follow-up             29             25
Physician Decision             9             3
Withdrawal by Subject             14             17
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 1403 1396 2799
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1403 participants 1396 participants 2799 participants
66.7  (9.93) 66.6  (9.90) 66.7  (9.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1403 participants 1396 participants 2799 participants
Female
671
  47.8%
698
  50.0%
1369
  48.9%
Male
732
  52.2%
698
  50.0%
1430
  51.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1403 participants 1396 participants 2799 participants
African American/African Heritage 3 5 8
Asian-Central/South Asian Heritage 5 6 11
Asian-East Asian Heritage 1 0 1
Asian-South East Asian Heritage 1 0 1
White-Arabic/North African Heritage 1 3 4
White-White/Caucasian/European Heritage 1387 1376 2763
Mixed Race 5 5 10
1.Primary Outcome
Title Mean Annual Rate of Moderate or Severe COPD Exacerbations
Hide Description 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
Time Frame Up to 54 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Analysis Population.
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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

Existing Maintenance Therapy:

  • Long acting bronchodilator therapy alone
  • ICS alone or in combination with a long acting bronchodilator
  • Triple maintenance therapy
Overall Number of Participants Analyzed 1134 1135
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per participant per year
1.90
(1.80 to 2.01)
1.74
(1.65 to 1.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.025
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.85 to 0.99
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) of Pneumonia During the Study
Hide Description 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.
Time Frame Up to 58 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) Population: Defined as all participants who were randomised and received at least one prescription of study medication
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
83 94
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority is demonstrated if the upper limit of the two-sided 95% confidence interval for the incidence ratio is less than 2.
Method of Estimation Estimation Parameter Incidence ratio
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.9 to 1.5
Estimation Comments Calculated as % of participants who had at least one SAE of pneumonia in the FF/VI group divided by the % of participants who had at least one SAE of pneumonia in the Usual Care group
3.Secondary Outcome
Title Mean Number of Serious Adverse Events of Pneumonia During the Study
Hide Description 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.
Time Frame Up to 58 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 1403 1396
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Mean Number of SAE
0.07
(0.06 to 0.09)
0.08
(0.06 to 0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.632
Comments [Not Specified]
Method Generalized linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.79 to 1.47
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to the First Serious Adverse Event of Pneumonia Occuring in a Year
Hide Description 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.
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
80 89
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.439
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.83 to 1.52
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of COPD-related Secondary Care Contacts Expressed as Least Square Mean
Hide Description 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.
Time Frame Up to 54 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
ExParticipants 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.
Overall Number of Participants Analyzed 1403 1396
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Contacts per participant per year
1.48
(1.30 to 1.67)
1.57
(1.39 to 1.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.488
Comments [Not Specified]
Method Generalized linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment ratio
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.89 to 1.27
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of COPD-related Primary Care Contacts Expressed Using Least Square Mean
Hide Description 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.
Time Frame Up to 54 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 1403 1396
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Contacts per participant per year
2.46
(2.34 to 2.58)
2.42
(2.30 to 2.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.622
Comments [Not Specified]
Method Generalized linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment ratio
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.92 to 1.05
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of All Secondary Care Contacts Expressed Using Least Square Mean
Hide Description 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.
Time Frame Up to 54 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 1403 1396
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Contacts per participant per year
9.36
(8.74 to 10.02)
9.81
(9.17 to 10.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.336
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.95 to 1.15
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of All Primary Care Contacts Expressed Using Least Square Mean
Hide Description 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.
Time Frame Up to 54 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 1403 1396
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Contacts per participant per year
18.88
(18.06 to 19.74)
21.20
(20.27 to 22.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment ratio
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
1.05 to 1.20
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to an Event of Discontinuation of Initial Therapy Occurring in a Year
Hide Description 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.
Time Frame Up to 364 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
219 374
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.89
Confidence Interval (2-Sided) 95%
1.60 to 2.23
Estimation Comments A hazard ratio <1 indicates a lower risk with FF/VI compared with Usual Care.
10.Secondary Outcome
Title Time to the Addition of a Further COPD Controller Medication Occurring in a Year
Hide Description 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.
Time Frame Up to 364 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
142 72
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cox proprotional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.37 to 0.66
Estimation Comments A hazard ratio <1 indicates a lower risk with FF/VI compared with Usual Care
11.Secondary Outcome
Title Time to First Moderate/Severe Exacerbations Occurring in a Year
Hide Description 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.
Time Frame Up to 364 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
977 947
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.111
Comments [Not Specified]
Method Cox porportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.85 to 1.02
Estimation Comments A hazard ratio <1 indicates a lower risk with FF/VI compared with Usual Care
12.Secondary Outcome
Title Time to First Moderate/Severe Exacerbations on Initial Therapy Occurring in a Year
Hide Description 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.
Time Frame Up to 364 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
943 852
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments [Not Specified]
Method Cox porportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.84 to 1.01
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Time to First Severe Exacerbations Occurring in a Year
Hide Description

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.

Time Frame Up to 364 days
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ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
97 122
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, FF/VI 100 mcg/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.98 to 1.66
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Fatal Serious Adverse Events of Pneumonia
Hide Description 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.
Time Frame Upto 58 weeks
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Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
13 13
15.Secondary Outcome
Title Number of Participants With Non-serious Adverse Drug Reactions (ADR)
Hide Description 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.
Time Frame Up to 54 weeks
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Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
88 192
16.Secondary Outcome
Title Number of Participants With Serious Adverse Events
Hide Description 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.
Time Frame Up to 56 weeks
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Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
383 404
17.Secondary Outcome
Title Number of Participants With Serious Adverse Drug Reactions
Hide Description 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.
Time Frame Upto 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 1403 1396
Measure Type: Number
Unit of Measure: Participants
10 23
Time Frame 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)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Usual Care FF/VI 100 mcg/25 mcg
Hide Arm/Group Description 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 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.
All-Cause Mortality
Usual Care FF/VI 100 mcg/25 mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Usual Care FF/VI 100 mcg/25 mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   383/1403 (27.30%)   404/1396 (28.94%) 
Blood and lymphatic system disorders     
Anaemia  1  6/1403 (0.43%)  5/1396 (0.36%) 
Microcytic anaemia  1  4/1403 (0.29%)  0/1396 (0.00%) 
Coagulopathy  1  1/1403 (0.07%)  1/1396 (0.07%) 
Normochromic normocytic anaemia  1  1/1403 (0.07%)  1/1396 (0.07%) 
Thrombocytopenia  1  0/1403 (0.00%)  2/1396 (0.14%) 
Agranulocytosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Iron deficiency anaemia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Neutropenia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pernicious anaemia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Cardiac disorders     
Atrial fibrillation  1  29/1403 (2.07%)  27/1396 (1.93%) 
Acute myocardial infarction  1  9/1403 (0.64%)  13/1396 (0.93%) 
Cardiac failure  1  11/1403 (0.78%)  10/1396 (0.72%) 
Acute coronary syndrome  1  12/1403 (0.86%)  5/1396 (0.36%) 
Angina pectoris  1  9/1403 (0.64%)  5/1396 (0.36%) 
Cardiac failure congestive  1  5/1403 (0.36%)  6/1396 (0.43%) 
Angina unstable  1  4/1403 (0.29%)  5/1396 (0.36%) 
Myocardial infarction  1  3/1403 (0.21%)  6/1396 (0.43%) 
Myocardial ischaemia  1  3/1403 (0.21%)  4/1396 (0.29%) 
Left ventricular dysfunction  1  4/1403 (0.29%)  2/1396 (0.14%) 
Atrial flutter  1  2/1403 (0.14%)  3/1396 (0.21%) 
Cor pulmonale  1  2/1403 (0.14%)  3/1396 (0.21%) 
Ventricular tachycardia  1  3/1403 (0.21%)  2/1396 (0.14%) 
Left ventricular failure  1  3/1403 (0.21%)  1/1396 (0.07%) 
Supraventricular tachycardia  1  0/1403 (0.00%)  4/1396 (0.29%) 
Arrhythmia  1  1/1403 (0.07%)  2/1396 (0.14%) 
Cardiac arrest  1  2/1403 (0.14%)  1/1396 (0.07%) 
Right ventricular failure  1  0/1403 (0.00%)  3/1396 (0.21%) 
Bradycardia  1  2/1403 (0.14%)  0/1396 (0.00%) 
Cardiac failure acute  1  0/1403 (0.00%)  2/1396 (0.14%) 
Cardiogenic shock  1  2/1403 (0.14%)  0/1396 (0.00%) 
Palpitations  1  2/1403 (0.14%)  0/1396 (0.00%) 
Pericardial effusion  1  1/1403 (0.07%)  1/1396 (0.07%) 
Sinus tachycardia  1  1/1403 (0.07%)  1/1396 (0.07%) 
Acute left ventricular failure  1  1/1403 (0.07%)  0/1396 (0.00%) 
Aortic valve incompetence  1  0/1403 (0.00%)  1/1396 (0.07%) 
Arteriosclerosis coronary artery  1  0/1403 (0.00%)  1/1396 (0.07%) 
Atrioventricular block complete  1  1/1403 (0.07%)  0/1396 (0.00%) 
Bradyarrhythmia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Cardiac ventricular thrombosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Cardiomyopathy  1  0/1403 (0.00%)  1/1396 (0.07%) 
Coronary artery disease  1  1/1403 (0.07%)  0/1396 (0.00%) 
Diastolic dysfunction  1  0/1403 (0.00%)  1/1396 (0.07%) 
Sinus bradycardia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Sinus node dysfunction  1  1/1403 (0.07%)  0/1396 (0.00%) 
Tachyarrhythmia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Tachycardia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Trifascicular block  1  1/1403 (0.07%)  0/1396 (0.00%) 
Ventricular arrhythmia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Ventricular fibrillation  1  1/1403 (0.07%)  0/1396 (0.00%) 
Congenital, familial and genetic disorders     
Phimosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Ear and labyrinth disorders     
Deafness unilateral  1  0/1403 (0.00%)  1/1396 (0.07%) 
Vertigo  1  1/1403 (0.07%)  0/1396 (0.00%) 
Endocrine disorders     
Hypothyroidism  1  1/1403 (0.07%)  2/1396 (0.14%) 
Hyperthyroidism  1  1/1403 (0.07%)  1/1396 (0.07%) 
Hyperparathyroidism primary  1  1/1403 (0.07%)  0/1396 (0.00%) 
Inappropriate antidiuretic hormone secretion  1  0/1403 (0.00%)  1/1396 (0.07%) 
Eye disorders     
Cataract  1  2/1403 (0.14%)  2/1396 (0.14%) 
Blindness unilateral  1  1/1403 (0.07%)  0/1396 (0.00%) 
Retinal artery occlusion  1  0/1403 (0.00%)  1/1396 (0.07%) 
Retinal detachment  1  1/1403 (0.07%)  0/1396 (0.00%) 
Vision blurred  1  1/1403 (0.07%)  0/1396 (0.00%) 
Vitreous haemorrhage  1  0/1403 (0.00%)  1/1396 (0.07%) 
Gastrointestinal disorders     
Constipation  1  5/1403 (0.36%)  3/1396 (0.21%) 
Diarrhoea  1  2/1403 (0.14%)  4/1396 (0.29%) 
Haematemesis  1  2/1403 (0.14%)  4/1396 (0.29%) 
Abdominal pain  1  4/1403 (0.29%)  1/1396 (0.07%) 
Gastritis  1  2/1403 (0.14%)  3/1396 (0.21%) 
Gastrointestinal haemorrhage  1  1/1403 (0.07%)  4/1396 (0.29%) 
Colitis ischaemic  1  1/1403 (0.07%)  3/1396 (0.21%) 
Colitis  1  1/1403 (0.07%)  2/1396 (0.14%) 
Pancreatitis  1  2/1403 (0.14%)  1/1396 (0.07%) 
Pancreatitis acute  1  1/1403 (0.07%)  2/1396 (0.14%) 
Pancreatitis chronic  1  1/1403 (0.07%)  2/1396 (0.14%) 
Upper gastrointestinal haemorrhage  1  2/1403 (0.14%)  1/1396 (0.07%) 
Vomiting  1  1/1403 (0.07%)  2/1396 (0.14%) 
Diverticulum  1  2/1403 (0.14%)  0/1396 (0.00%) 
Dyspepsia  1  1/1403 (0.07%)  1/1396 (0.07%) 
Gastrooesophageal reflux disease  1  0/1403 (0.00%)  2/1396 (0.14%) 
Intestinal obstruction  1  1/1403 (0.07%)  1/1396 (0.07%) 
Oesophageal ulcer  1  2/1403 (0.14%)  0/1396 (0.00%) 
Ascites  1  0/1403 (0.00%)  1/1396 (0.07%) 
Barrett’s oesophagus  1  1/1403 (0.07%)  0/1396 (0.00%) 
Coeliac disease  1  1/1403 (0.07%)  0/1396 (0.00%) 
Diverticulum intestinal  1  1/1403 (0.07%)  0/1396 (0.00%) 
Duodenal ulcer  1  0/1403 (0.00%)  1/1396 (0.07%) 
Duodenal ulcer perforation  1  1/1403 (0.07%)  0/1396 (0.00%) 
Duodenitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Dyskinesia oesophageal  1  0/1403 (0.00%)  1/1396 (0.07%) 
Dysphagia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Food poisoning  1  0/1403 (0.00%)  1/1396 (0.07%) 
Gastric dysplasia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Gastric ulcer  1  1/1403 (0.07%)  0/1396 (0.00%) 
Gastrointestinal hypomotility  1  1/1403 (0.07%)  0/1396 (0.00%) 
Intestinal ischaemia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Large intestine perforation  1  1/1403 (0.07%)  0/1396 (0.00%) 
Lower gastrointestinal haemorrhage  1  1/1403 (0.07%)  0/1396 (0.00%) 
Obstruction gastric  1  0/1403 (0.00%)  1/1396 (0.07%) 
Oesophageal spasm  1  1/1403 (0.07%)  0/1396 (0.00%) 
Oesophagitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Pancreatic insufficiency  1  0/1403 (0.00%)  1/1396 (0.07%) 
Small intestinal obstruction  1  0/1403 (0.00%)  1/1396 (0.07%) 
Intra-abdominal haemorrhage  1  0/1403 (0.00%)  2/1396 (0.14%) 
Abdominal pain upper  1  0/1403 (0.00%)  1/1396 (0.07%) 
General disorders     
Chest pain  1  8/1403 (0.57%)  1/1396 (0.07%) 
Non-cardiac chest pain  1  1/1403 (0.07%)  4/1396 (0.29%) 
Cyst  1  1/1403 (0.07%)  0/1396 (0.00%) 
Hypothermia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Multi-organ failure  1  0/1403 (0.00%)  1/1396 (0.07%) 
Stent-graft endoleak  1  0/1403 (0.00%)  1/1396 (0.07%) 
Unintentional medical device removal  1  1/1403 (0.07%)  0/1396 (0.00%) 
Vascular stent occlusion  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hepatobiliary disorders     
Cholecystitis  1  3/1403 (0.21%)  2/1396 (0.14%) 
Hepatic function abnormal  1  3/1403 (0.21%)  2/1396 (0.14%) 
Cholecystitis acute  1  1/1403 (0.07%)  3/1396 (0.21%) 
Cholangitis  1  0/1403 (0.00%)  3/1396 (0.21%) 
Cholelithiasis  1  0/1403 (0.00%)  3/1396 (0.21%) 
Alcoholic liver disease  1  0/1403 (0.00%)  1/1396 (0.07%) 
Autoimmune hepatitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Gallbladder perforation  1  1/1403 (0.07%)  0/1396 (0.00%) 
Hepatic cirrhosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hepatic failure  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hepatitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Jaundice cholestatic  1  0/1403 (0.00%)  1/1396 (0.07%) 
Immune system disorders     
Hypersensitivity  1  2/1403 (0.14%)  2/1396 (0.14%) 
Anaphylactic reaction  1  0/1403 (0.00%)  2/1396 (0.14%) 
Drug hypersensitivity  1  2/1403 (0.14%)  0/1396 (0.00%) 
Allergic granulomatous angiitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Infections and infestations     
Pneumonia  1  81/1403 (5.77%)  89/1396 (6.38%) 
Infective exacerbation of chronic obstructive airway disease  1  47/1403 (3.35%)  50/1396 (3.58%) 
Cellulitis  1  9/1403 (0.64%)  14/1396 (1.00%) 
Lower respiratory tract infection  1  10/1403 (0.71%)  12/1396 (0.86%) 
Urinary tract infection  1  12/1403 (0.86%)  9/1396 (0.64%) 
Sepsis  1  10/1403 (0.71%)  9/1396 (0.64%) 
Gastroenteritis  1  4/1403 (0.29%)  3/1396 (0.21%) 
Urosepsis  1  1/1403 (0.07%)  4/1396 (0.29%) 
Abdominal sepsis  1  2/1403 (0.14%)  2/1396 (0.14%) 
Biliary sepsis  1  2/1403 (0.14%)  2/1396 (0.14%) 
Bronchopulmonary aspergillosis  1  1/1403 (0.07%)  3/1396 (0.21%) 
Gastroenteritis viral  1  2/1403 (0.14%)  2/1396 (0.14%) 
Osteomyelitis  1  3/1403 (0.21%)  1/1396 (0.07%) 
Clostridium difficile infection  1  2/1403 (0.14%)  1/1396 (0.07%) 
Anal abscess  1  1/1403 (0.07%)  1/1396 (0.07%) 
Diverticulitis  1  0/1403 (0.00%)  2/1396 (0.14%) 
Endocarditis  1  2/1403 (0.14%)  0/1396 (0.00%) 
Neutropenic sepsis  1  0/1403 (0.00%)  2/1396 (0.14%) 
Ophthalmic herpes zoster  1  1/1403 (0.07%)  1/1396 (0.07%) 
Upper respiratory tract infection  1  0/1403 (0.00%)  2/1396 (0.14%) 
Abscess limb  1  0/1403 (0.00%)  1/1396 (0.07%) 
Abscess oral  1  1/1403 (0.07%)  0/1396 (0.00%) 
Appendicitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Arthritis bacterial  1  0/1403 (0.00%)  1/1396 (0.07%) 
Arthritis infective  1  1/1403 (0.07%)  0/1396 (0.00%) 
Aspergillus infection  1  1/1403 (0.07%)  0/1396 (0.00%) 
Atypical mycobacterial infection  1  0/1403 (0.00%)  1/1396 (0.07%) 
Bronchitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Clostridium difficile colitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Device related infection  1  0/1403 (0.00%)  1/1396 (0.07%) 
Empyema  1  1/1403 (0.07%)  0/1396 (0.00%) 
Encephalitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Endophthalmitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Haematoma infection  1  0/1403 (0.00%)  1/1396 (0.07%) 
Herpes virus infection  1  0/1403 (0.00%)  1/1396 (0.07%) 
Herpes zoster  1  1/1403 (0.07%)  0/1396 (0.00%) 
Herpes zoster meningoencephalitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Infective exacerbation of bronchiectasis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Influenza  1  1/1403 (0.07%)  0/1396 (0.00%) 
Localised infection  1  0/1403 (0.00%)  1/1396 (0.07%) 
Lung abscess  1  1/1403 (0.07%)  0/1396 (0.00%) 
Lymphangitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Mycetoma mycotic  1  1/1403 (0.07%)  0/1396 (0.00%) 
Oesophageal candidiasis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Oral candidiasis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Orchitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Otitis externa  1  1/1403 (0.07%)  0/1396 (0.00%) 
Pelvic abscess  1  0/1403 (0.00%)  1/1396 (0.07%) 
Peritonitis bacterial  1  0/1403 (0.00%)  1/1396 (0.07%) 
Peritonsillar abscess  1  1/1403 (0.07%)  0/1396 (0.00%) 
Pneumonia streptococcal  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pulmonary tuberculosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pyelonephritis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Pyelonephritis acute  1  0/1403 (0.00%)  1/1396 (0.07%) 
Septic embolus  1  1/1403 (0.07%)  0/1396 (0.00%) 
Septic shock  1  0/1403 (0.00%)  1/1396 (0.07%) 
Subcutaneous abscess  1  1/1403 (0.07%)  0/1396 (0.00%) 
Tonsillitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Varicella zoster virus infection  1  0/1403 (0.00%)  1/1396 (0.07%) 
Viral labyrinthitis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  9/1403 (0.64%)  15/1396 (1.07%) 
Rib fracture  1  9/1403 (0.64%)  5/1396 (0.36%) 
Radius fracture  1  5/1403 (0.36%)  8/1396 (0.57%) 
Head injury  1  2/1403 (0.14%)  8/1396 (0.57%) 
Hand fracture  1  4/1403 (0.29%)  4/1396 (0.29%) 
Humerus fracture  1  3/1403 (0.21%)  5/1396 (0.36%) 
Ankle fracture  1  5/1403 (0.36%)  2/1396 (0.14%) 
Femoral neck fracture  1  3/1403 (0.21%)  4/1396 (0.29%) 
Alcohol poisoning  1  4/1403 (0.29%)  2/1396 (0.14%) 
Foot fracture  1  2/1403 (0.14%)  4/1396 (0.29%) 
Intentional overdose  1  2/1403 (0.14%)  4/1396 (0.29%) 
Overdose  1  3/1403 (0.21%)  3/1396 (0.21%) 
Fibula fracture  1  2/1403 (0.14%)  2/1396 (0.14%) 
Joint dislocation  1  3/1403 (0.21%)  1/1396 (0.07%) 
Wrist fracture  1  2/1403 (0.14%)  2/1396 (0.14%) 
Femur fracture  1  2/1403 (0.14%)  1/1396 (0.07%) 
Thoracic vertebral fracture  1  3/1403 (0.21%)  0/1396 (0.00%) 
Ulna fracture  1  0/1403 (0.00%)  3/1396 (0.21%) 
Clavicle fracture  1  1/1403 (0.07%)  1/1396 (0.07%) 
Facial bones fracture  1  0/1403 (0.00%)  2/1396 (0.14%) 
Lumbar vertebral fracture  1  0/1403 (0.00%)  2/1396 (0.14%) 
Procedural pain  1  2/1403 (0.14%)  0/1396 (0.00%) 
Spinal compression fracture  1  0/1403 (0.00%)  2/1396 (0.14%) 
Spinal fracture  1  1/1403 (0.07%)  1/1396 (0.07%) 
Subdural haematoma  1  0/1403 (0.00%)  2/1396 (0.14%) 
Upper limb fracture  1  2/1403 (0.14%)  0/1396 (0.00%) 
Accidental overdose  1  1/1403 (0.07%)  0/1396 (0.00%) 
Brachial plexus injury  1  1/1403 (0.07%)  0/1396 (0.00%) 
Cardiac valve rupture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Chemical injury  1  0/1403 (0.00%)  1/1396 (0.07%) 
Chest injury  1  1/1403 (0.07%)  0/1396 (0.00%) 
Contrast media reaction  1  0/1403 (0.00%)  1/1396 (0.07%) 
Craniocerebral injury  1  0/1403 (0.00%)  1/1396 (0.07%) 
Forearm fracture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Foreign body aspiration  1  1/1403 (0.07%)  0/1396 (0.00%) 
Fracture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hip fracture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Open fracture  1  1/1403 (0.07%)  0/1396 (0.00%) 
Patella fracture  1  1/1403 (0.07%)  0/1396 (0.00%) 
Pelvic fracture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pneumothorax traumatic  1  0/1403 (0.00%)  1/1396 (0.07%) 
Post procedural haematoma  1  0/1403 (0.00%)  1/1396 (0.07%) 
Post procedural haemorrhage  1  1/1403 (0.07%)  0/1396 (0.00%) 
Procedural complication  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pubis fracture  1  1/1403 (0.07%)  0/1396 (0.00%) 
Radiation mucositis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Soft tissue injury  1  0/1403 (0.00%)  1/1396 (0.07%) 
Splenic rupture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Stress fracture  1  0/1403 (0.00%)  1/1396 (0.07%) 
Transfusion reaction  1  0/1403 (0.00%)  1/1396 (0.07%) 
Urethral injury  1  0/1403 (0.00%)  1/1396 (0.07%) 
Investigations     
Liver function test abnormal  1  6/1403 (0.43%)  15/1396 (1.07%) 
Renal function test abnormal  1  9/1403 (0.64%)  12/1396 (0.86%) 
Electrocardiogram QT prolonged  1  2/1403 (0.14%)  2/1396 (0.14%) 
International normalised ratio increased  1  2/1403 (0.14%)  1/1396 (0.07%) 
Weight decreased  1  1/1403 (0.07%)  2/1396 (0.14%) 
Haemoglobin decreased  1  1/1403 (0.07%)  1/1396 (0.07%) 
Alanine aminotransferase increased  1  0/1403 (0.00%)  1/1396 (0.07%) 
Blood electrolytes abnormal  1  1/1403 (0.07%)  0/1396 (0.00%) 
Prostatic specific antigen increased  1  0/1403 (0.00%)  1/1396 (0.07%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  7/1403 (0.50%)  7/1396 (0.50%) 
Electrolyte imbalance  1  6/1403 (0.43%)  4/1396 (0.29%) 
Dehydration  1  2/1403 (0.14%)  6/1396 (0.43%) 
Metabolic acidosis  1  3/1403 (0.21%)  5/1396 (0.36%) 
Type 2 diabetes mellitus  1  5/1403 (0.36%)  3/1396 (0.21%) 
Hyperkalaemia  1  1/1403 (0.07%)  4/1396 (0.29%) 
Gout  1  2/1403 (0.14%)  2/1396 (0.14%) 
Hypokalaemia  1  2/1403 (0.14%)  2/1396 (0.14%) 
Hypocalcaemia  1  1/1403 (0.07%)  2/1396 (0.14%) 
Hypomagnesaemia  1  2/1403 (0.14%)  1/1396 (0.07%) 
Diabetes mellitus  1  1/1403 (0.07%)  1/1396 (0.07%) 
Diabetic ketoacidosis  1  2/1403 (0.14%)  0/1396 (0.00%) 
Hypercalcaemia  1  0/1403 (0.00%)  2/1396 (0.14%) 
Hypoglycaemia  1  0/1403 (0.00%)  2/1396 (0.14%) 
Cachexia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Diabetes mellitus inadequate control  1  0/1403 (0.00%)  1/1396 (0.07%) 
Haemochromatosis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Hyperosmolar hyperglycaemic state  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hypophagia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hypophosphataemia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Malnutrition  1  1/1403 (0.07%)  0/1396 (0.00%) 
Obesity  1  0/1403 (0.00%)  1/1396 (0.07%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain  1  6/1403 (0.43%)  2/1396 (0.14%) 
Osteoporosis  1  1/1403 (0.07%)  3/1396 (0.21%) 
Back pain  1  3/1403 (0.21%)  0/1396 (0.00%) 
Muscle necrosis  1  0/1403 (0.00%)  2/1396 (0.14%) 
Muscular weakness  1  2/1403 (0.14%)  0/1396 (0.00%) 
Neck pain  1  1/1403 (0.07%)  1/1396 (0.07%) 
Osteoarthritis  1  2/1403 (0.14%)  0/1396 (0.00%) 
Arthritis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Bursitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Compartment syndrome  1  0/1403 (0.00%)  1/1396 (0.07%) 
Haemarthrosis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Intervertebral disc protrusion  1  1/1403 (0.07%)  0/1396 (0.00%) 
Lumbar spinal stenosis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Mobility decreased  1  0/1403 (0.00%)  1/1396 (0.07%) 
Muscle spasms  1  0/1403 (0.00%)  1/1396 (0.07%) 
Musculoskeletal pain  1  0/1403 (0.00%)  1/1396 (0.07%) 
Myositis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Rheumatoid arthritis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Soft tissue swelling  1  1/1403 (0.07%)  0/1396 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  7/1403 (0.50%)  10/1396 (0.72%) 
Metastases to liver  1  3/1403 (0.21%)  2/1396 (0.14%) 
Breast cancer  1  1/1403 (0.07%)  3/1396 (0.21%) 
Basal cell carcinoma  1  2/1403 (0.14%)  1/1396 (0.07%) 
Bladder neoplasm  1  1/1403 (0.07%)  2/1396 (0.14%) 
Laryngeal squamous cell carcinoma  1  1/1403 (0.07%)  2/1396 (0.14%) 
Lung cancer metastatic  1  1/1403 (0.07%)  2/1396 (0.14%) 
Metastatic neoplasm  1  0/1403 (0.00%)  3/1396 (0.21%) 
Rectal cancer  1  3/1403 (0.21%)  0/1396 (0.00%) 
Squamous cell carcinoma of lung  1  2/1403 (0.14%)  1/1396 (0.07%) 
Adenocarcinoma of colon  1  2/1403 (0.14%)  0/1396 (0.00%) 
Bladder cancer  1  1/1403 (0.07%)  1/1396 (0.07%) 
Colon neoplasm  1  2/1403 (0.14%)  0/1396 (0.00%) 
Invasive ductal breast carcinoma  1  0/1403 (0.00%)  2/1396 (0.14%) 
Lung adenocarcinoma  1  0/1403 (0.00%)  2/1396 (0.14%) 
Lymphoma  1  1/1403 (0.07%)  1/1396 (0.07%) 
Renal neoplasm  1  0/1403 (0.00%)  2/1396 (0.14%) 
Squamous cell carcinoma  1  2/1403 (0.14%)  0/1396 (0.00%) 
Bowen’s disease  1  1/1403 (0.07%)  0/1396 (0.00%) 
Brain neoplasm  1  0/1403 (0.00%)  1/1396 (0.07%) 
Bronchial carcinoma  1  0/1403 (0.00%)  1/1396 (0.07%) 
Carcinoma in situ of skin  1  1/1403 (0.07%)  0/1396 (0.00%) 
Carotid body tumour  1  1/1403 (0.07%)  0/1396 (0.00%) 
Chronic lymphocytic leukaemia  1  1/1403 (0.07%)  0/1396 (0.00%) 
Chronic lymphocytic leukaemia recurrent  1  0/1403 (0.00%)  1/1396 (0.07%) 
Colon adenoma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Gastrointestinal carcinoma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Gastrointestinal tract adenoma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Glioblastoma multiforme  1  0/1403 (0.00%)  1/1396 (0.07%) 
Glottis carcinoma  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hepatic cancer metastatic  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hepatic neoplasm  1  1/1403 (0.07%)  0/1396 (0.00%) 
Lung carcinoma cell type unspecified recurrent  1  0/1403 (0.00%)  1/1396 (0.07%) 
Lung squamous cell carcinoma recurrent  1  0/1403 (0.00%)  1/1396 (0.07%) 
Lung squamous cell carcinoma stage 0  1  0/1403 (0.00%)  1/1396 (0.07%) 
Lung squamous cell carcinoma stage IV  1  0/1403 (0.00%)  1/1396 (0.07%) 
Mantle cell lymphoma  1  0/1403 (0.00%)  1/1396 (0.07%) 
Meningioma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Metastases to lung  1  1/1403 (0.07%)  0/1396 (0.00%) 
Metastases to lymph nodes  1  1/1403 (0.07%)  0/1396 (0.00%) 
Metastatic malignant melanoma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Myelodysplastic syndrome  1  1/1403 (0.07%)  0/1396 (0.00%) 
Neuroendocrine tumour  1  1/1403 (0.07%)  0/1396 (0.00%) 
Oesophageal carcinoma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Pancreatic carcinoma  1  1/1403 (0.07%)  0/1396 (0.00%) 
Prostate cancer  1  0/1403 (0.00%)  1/1396 (0.07%) 
Prostate cancer recurrent  1  1/1403 (0.07%)  0/1396 (0.00%) 
Prostatic adenoma  1  0/1403 (0.00%)  1/1396 (0.07%) 
Refractory anaemia with an excess of blasts  1  0/1403 (0.00%)  1/1396 (0.07%) 
Small cell lung cancer  1  1/1403 (0.07%)  0/1396 (0.00%) 
Ureteral neoplasm  1  0/1403 (0.00%)  1/1396 (0.07%) 
Ureteric cancer  1  0/1403 (0.00%)  1/1396 (0.07%) 
Nervous system disorders     
Syncope  1  10/1403 (0.71%)  11/1396 (0.79%) 
Transient ischaemic attack  1  9/1403 (0.64%)  5/1396 (0.36%) 
Ischaemic stroke  1  6/1403 (0.43%)  3/1396 (0.21%) 
Seizure  1  4/1403 (0.29%)  3/1396 (0.21%) 
Cerebrovascular accident  1  5/1403 (0.36%)  1/1396 (0.07%) 
Cerebrovascular disorder  1  2/1403 (0.14%)  2/1396 (0.14%) 
Cerebral infarction  1  1/1403 (0.07%)  2/1396 (0.14%) 
Brain injury  1  2/1403 (0.14%)  0/1396 (0.00%) 
Carotid artery stenosis  1  1/1403 (0.07%)  1/1396 (0.07%) 
Dizziness  1  1/1403 (0.07%)  1/1396 (0.07%) 
Loss of consciousness  1  1/1403 (0.07%)  1/1396 (0.07%) 
Migraine  1  1/1403 (0.07%)  1/1396 (0.07%) 
VIth nerve paralysis  1  0/1403 (0.00%)  2/1396 (0.14%) 
Vocal cord paresis  1  0/1403 (0.00%)  2/1396 (0.14%) 
Basal ganglia infarction  1  1/1403 (0.07%)  0/1396 (0.00%) 
Brain mass  1  1/1403 (0.07%)  0/1396 (0.00%) 
Carotid artery aneurysm  1  0/1403 (0.00%)  1/1396 (0.07%) 
Carotid artery disease  1  1/1403 (0.07%)  0/1396 (0.00%) 
Carotid sinus syndrome  1  1/1403 (0.07%)  0/1396 (0.00%) 
Carpal tunnel syndrome  1  1/1403 (0.07%)  0/1396 (0.00%) 
Cerebral haemorrhage  1  0/1403 (0.00%)  1/1396 (0.07%) 
Cervical myelopathy  1  0/1403 (0.00%)  1/1396 (0.07%) 
Dementia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Dementia with Lewy bodies  1  0/1403 (0.00%)  1/1396 (0.07%) 
Drug withdrawal convulsions  1  1/1403 (0.07%)  0/1396 (0.00%) 
Epilepsy  1  0/1403 (0.00%)  1/1396 (0.07%) 
Generalised tonic-clonic seizure  1  0/1403 (0.00%)  1/1396 (0.07%) 
Haemorrhage intracranial  1  0/1403 (0.00%)  1/1396 (0.07%) 
Headache  1  1/1403 (0.07%)  0/1396 (0.00%) 
Hepatic encephalopathy  1  1/1403 (0.07%)  0/1396 (0.00%) 
Hydrocephalus  1  0/1403 (0.00%)  1/1396 (0.07%) 
Meningism  1  1/1403 (0.07%)  0/1396 (0.00%) 
Peroneal nerve palsy  1  1/1403 (0.07%)  0/1396 (0.00%) 
Presyncope  1  0/1403 (0.00%)  1/1396 (0.07%) 
Radiculitis brachial  1  0/1403 (0.00%)  1/1396 (0.07%) 
Radiculopathy  1  0/1403 (0.00%)  1/1396 (0.07%) 
Sedation  1  0/1403 (0.00%)  1/1396 (0.07%) 
Subarachnoid haemorrhage  1  0/1403 (0.00%)  1/1396 (0.07%) 
Unresponsive to stimuli  1  1/1403 (0.07%)  0/1396 (0.00%) 
VIIth nerve paralysis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Vascular dementia  1  0/1403 (0.00%)  1/1396 (0.07%) 
Psychiatric disorders     
Delirium  1  2/1403 (0.14%)  4/1396 (0.29%) 
Alcohol withdrawal syndrome  1  1/1403 (0.07%)  3/1396 (0.21%) 
Confusional state  1  2/1403 (0.14%)  1/1396 (0.07%) 
Depression  1  3/1403 (0.21%)  0/1396 (0.00%) 
Suicidal ideation  1  1/1403 (0.07%)  2/1396 (0.14%) 
Anxiety  1  2/1403 (0.14%)  0/1396 (0.00%) 
Delirium tremens  1  0/1403 (0.00%)  1/1396 (0.07%) 
Major depression  1  0/1403 (0.00%)  1/1396 (0.07%) 
Self-injurious ideation  1  1/1403 (0.07%)  0/1396 (0.00%) 
Suicide attempt  1  0/1403 (0.00%)  1/1396 (0.07%) 
Renal and urinary disorders     
Acute kidney injury  1  16/1403 (1.14%)  23/1396 (1.65%) 
Renal impairment  1  7/1403 (0.50%)  10/1396 (0.72%) 
Urinary retention  1  7/1403 (0.50%)  8/1396 (0.57%) 
Chronic kidney disease  1  5/1403 (0.36%)  2/1396 (0.14%) 
Haematuria  1  3/1403 (0.21%)  0/1396 (0.00%) 
Renal artery stenosis  1  1/1403 (0.07%)  1/1396 (0.07%) 
Renal colic  1  2/1403 (0.14%)  0/1396 (0.00%) 
Acute prerenal failure  1  1/1403 (0.07%)  0/1396 (0.00%) 
Calculus ureteric  1  0/1403 (0.00%)  1/1396 (0.07%) 
Hydronephrosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Nephrolithiasis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Renal disorder  1  1/1403 (0.07%)  0/1396 (0.00%) 
Renal mass  1  0/1403 (0.00%)  1/1396 (0.07%) 
Sterile pyuria  1  0/1403 (0.00%)  1/1396 (0.07%) 
Reproductive system and breast disorders     
Postmenopausal haemorrhage  1  1/1403 (0.07%)  0/1396 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  70/1403 (4.99%)  86/1396 (6.16%) 
Respiratory failure  1  24/1403 (1.71%)  15/1396 (1.07%) 
Pulmonary oedema  1  9/1403 (0.64%)  5/1396 (0.36%) 
Bronchiectasis  1  4/1403 (0.29%)  6/1396 (0.43%) 
Pulmonary embolism  1  2/1403 (0.14%)  8/1396 (0.57%) 
Epistaxis  1  3/1403 (0.21%)  4/1396 (0.29%) 
Asthma  1  2/1403 (0.14%)  2/1396 (0.14%) 
Pneumonia aspiration  1  1/1403 (0.07%)  3/1396 (0.21%) 
Haemoptysis  1  1/1403 (0.07%)  2/1396 (0.14%) 
Pneumothorax  1  2/1403 (0.14%)  1/1396 (0.07%) 
Pickwickian syndrome  1  1/1403 (0.07%)  1/1396 (0.07%) 
Pleural effusion  1  2/1403 (0.14%)  0/1396 (0.00%) 
Pulmonary hypertension  1  0/1403 (0.00%)  2/1396 (0.14%) 
Respiratory arrest  1  1/1403 (0.07%)  1/1396 (0.07%) 
Stridor  1  0/1403 (0.00%)  2/1396 (0.14%) 
Atelectasis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Bronchial secretion retention  1  0/1403 (0.00%)  1/1396 (0.07%) 
Bronchospasm  1  1/1403 (0.07%)  0/1396 (0.00%) 
Dyspnoea  1  0/1403 (0.00%)  1/1396 (0.07%) 
Laryngeal oedema  1  1/1403 (0.07%)  0/1396 (0.00%) 
Lung disorder  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pleural fibrosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Pneumonitis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Respiratory acidosis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Sputum retention  1  0/1403 (0.00%)  1/1396 (0.07%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  3/1403 (0.21%)  0/1396 (0.00%) 
Dermatitis  1  1/1403 (0.07%)  1/1396 (0.07%) 
Dermatitis allergic  1  0/1403 (0.00%)  2/1396 (0.14%) 
Eczema  1  1/1403 (0.07%)  1/1396 (0.07%) 
Miliaria  1  1/1403 (0.07%)  0/1396 (0.00%) 
Rash  1  1/1403 (0.07%)  0/1396 (0.00%) 
Skin ulcer  1  1/1403 (0.07%)  0/1396 (0.00%) 
Surgical and medical procedures     
Hospitalisation  1  2/1403 (0.14%)  0/1396 (0.00%) 
Carotid endarterectomy  1  0/1403 (0.00%)  1/1396 (0.07%) 
Vascular disorders     
Deep vein thrombosis  1  3/1403 (0.21%)  9/1396 (0.64%) 
Aortic aneurysm  1  3/1403 (0.21%)  3/1396 (0.21%) 
Aortic stenosis  1  2/1403 (0.14%)  4/1396 (0.29%) 
Haematoma  1  3/1403 (0.21%)  2/1396 (0.14%) 
Orthostatic hypotension  1  0/1403 (0.00%)  4/1396 (0.29%) 
Hypotension  1  3/1403 (0.21%)  0/1396 (0.00%) 
Peripheral ischaemia  1  2/1403 (0.14%)  1/1396 (0.07%) 
Angiodysplasia  1  1/1403 (0.07%)  1/1396 (0.07%) 
Lymphoedema  1  1/1403 (0.07%)  1/1396 (0.07%) 
Aortic aneurysm rupture  1  1/1403 (0.07%)  0/1396 (0.00%) 
Aortic dissection  1  1/1403 (0.07%)  0/1396 (0.00%) 
Aortic thrombosis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Blood pressure inadequately controlled  1  1/1403 (0.07%)  0/1396 (0.00%) 
Circulatory collapse  1  0/1403 (0.00%)  1/1396 (0.07%) 
Extremity necrosis  1  1/1403 (0.07%)  0/1396 (0.00%) 
Femoral artery occlusion  1  0/1403 (0.00%)  1/1396 (0.07%) 
Peripheral artery stenosis  1  0/1403 (0.00%)  1/1396 (0.07%) 
Peripheral vascular disorder  1  1/1403 (0.07%)  0/1396 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Usual Care FF/VI 100 mcg/25 mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   40/1403 (2.85%)   56/1396 (4.01%) 
Infections and infestations     
Oral candidiasis  1 [1]  40/1403 (2.85%)  56/1396 (4.01%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.1
[1]
In this study, only information regarding non- serious adverse drug reactions (ADRs) and serious adverse events (SAEs) were detected, documented and reported.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01551758     History of Changes
Other Study ID Numbers: 115151
First Submitted: March 1, 2012
First Posted: March 13, 2012
Results First Submitted: September 5, 2016
Results First Posted: March 7, 2017
Last Update Posted: May 31, 2017