Trial Outcomes & Findings for DETERMINE-reduced - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction (NCT NCT03877237)

Last Updated: 2021-05-05

Results Overview

Change from baseline in KCCQ-TSS was defined as the endpoint value at week 16 minus the baseline value. KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The KCCQ-TSS incorporates the symptom frequency (4 items) and symptom burden (3 items) domains into a single summary score. The score is transformed to a range of 0-100, in which a higher score reflects better health status. Baseline value is the last value on or prior to the randomization visit. Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive. In rank ANCOVA and HL estimation, multiple imputation was performed on missing values for participants who were alive at the visit at week 16 but did not have KCCQ-TSS values.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

313 participants

Primary outcome timeframe

At baseline and at week 16 or death before week 16

Results posted on

2021-05-05

Participant Flow

Participant milestones

Participant milestones
Measure	Dapa 10mg Dapagliflozin 10 mg, given once daily per oral use.	Placebo Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Study STARTED	156	157
Overall Study Treated	156	157
Overall Study COMPLETED	151	151
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dapa 10mg Dapagliflozin 10 mg, given once daily per oral use.	Placebo Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Study Adverse Event	1	2
Overall Study Death	3	2
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

DETERMINE-reduced - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dapa 10mg n=156 Participants Dapagliflozin 10 mg, given once daily per oral use.	Placebo n=157 Participants Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.	Total n=313 Participants Total of all reporting groups
Age, Continuous	68.4 Years STANDARD_DEVIATION 9.84 • n=5 Participants	67.3 Years STANDARD_DEVIATION 10.95 • n=7 Participants	67.8 Years STANDARD_DEVIATION 10.41 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	35 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	111 Participants n=5 Participants	122 Participants n=7 Participants	233 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	21 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	138 Participants n=5 Participants	136 Participants n=7 Participants	274 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	100 Participants n=5 Participants	98 Participants n=7 Participants	198 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	19 Participants n=5 Participants	27 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Other	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline and at week 16 or death before week 16

Population: Full Analysis Set: All participants that were randomized, regardless of whether treated or not.

Outcome measures

Outcome measures
Measure	Dapa 10mg n=156 Participants Dapagliflozin 10 mg, given once daily per oral use.	Placebo n=157 Participants Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Change From Baseline in Kansas-City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 16 (Higher Scores Represent Less HF Symptom Frequency and Burden).	2.08 Score on a scale Interval -4.17 to 14.58	0.00 Score on a scale Interval -10.42 to 9.38

PRIMARY outcome

Timeframe: At baseline and at week 16 or death before week 16

Population: Full Analysis Set: All participants that were randomized, regardless of whether treated or not, excluding participants with non-calculable baseline or week 16 KCCQ-PLS.

Change from baseline in KCCQ-PLS was defined as the endpoint value at week 16 minus the baseline value. KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The KCCQ-PLS incorporates the 6 physical limitation items into a single score. The score is transformed to a range of 0-100, in which a higher score reflects better health status. Baseline value is the last value on or prior to the randomization visit. Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive. Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive. In rank ANCOVA and HL estimation, multiple imputation was performed on missing values for participants who were alive at the visit at week 16 but did not have KCCQ-PLS values.

Outcome measures

Outcome measures
Measure	Dapa 10mg n=153 Participants Dapagliflozin 10 mg, given once daily per oral use.	Placebo n=156 Participants Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Change From Baseline in Kansas-City Cardiomyopathy Questionnaire-Physical Limitation Score (KCCQ-PLS) at Week 16 (Higher Scores Represent Less Physical Limitation Due to HF)	4.17 Score on a scale Interval -4.17 to 12.5	0.00 Score on a scale Interval -8.33 to 8.33

PRIMARY outcome

Timeframe: At baseline and at week 16 or death prior to week 16

Population: Full Analysis Set: All participants that were randomized, regardless of whether treated or not.

Change from baseline in 6-minute walk distance (6MWD) (exercise capacity) at week 16 was defined as the distance walked in 6 minutes at week 16 minus the baseline value. Baseline value is the last value on or prior to the randomization visit. Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive. In rank ANCOVA and HL estimation, multiple imputation was performed on missing values for participants who were alive at the visit at week 16 but did not have 6MWD values.

Outcome measures

Outcome measures
Measure	Dapa 10mg n=156 Participants Dapagliflozin 10 mg, given once daily per oral use.	Placebo n=157 Participants Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Change From Baseline in 6-minute Walk Distance (6MWD) at Week 16 (Larger Distances Represent Better Functional Capacity).	20.0 meters Interval -2.0 to 42.0	13.5 meters Interval -12.5 to 46.5

SECONDARY outcome

Timeframe: At baseline and at end of study or death before week 16.

Population: Full Analysis Set: All participants that were randomized, regardless of whether treated or not, including participants from investigator sites having wearable activity monitor data collected.

Change from baseline at the end of the study in total time spent in light to vigorous physical activity (LVPA), as assessed using a wearable activity monitor, was defined as the total time \[per day\] spent in LVPA at the end of the study minus the baseline value. Baseline is the 7 day period starting on the day of enrolment and ending before randomization. End of study is defined as the period starting on the day of week 14 and prior to the week 16 visit. Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive.

Outcome measures

Outcome measures
Measure	Dapa 10mg n=42 Participants Dapagliflozin 10 mg, given once daily per oral use.	Placebo n=34 Participants Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Change From Baseline at the End of the Study in the Total Time Spent in Light to Vigorous Physical Activity, as Assessed Using a Wearable Activity Monitor (Accelerometer).	-0.19 hours Interval -0.57 to 0.15	-0.15 hours Interval -0.68 to 0.53

Adverse Events

Dapa 10mg

Serious events: 19 serious events

Other events: 0 other events

Deaths: 3 deaths

Placebo

Serious events: 23 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Łyżwa, Dawid

Astrazeneca

Phone: +48 882 345 259

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Dapa 10mg n=156 participants at risk Dapagliflozin 10 mg, given once daily per oral use.	Placebo n=157 participants at risk Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Cardiac disorders Cardiac failure	1.9% 3/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	3.8% 6/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Cardiac arrest	1.3% 2/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Acute myocardial infarction	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	1.3% 2/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	1.3% 2/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure acute	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	2.5% 4/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Left ventricular failure	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	1.3% 2/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Cardiac disorders Ventricular tachycardia	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	1.3% 2/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Infections and infestations Chagas' cardiomyopathy	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Infections and infestations Erysipelas	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Infections and infestations Sepsis	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Infections and infestations Infected skin ulcer	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
General disorders Multiple organ dysfunction syndrome	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
General disorders Non-cadiac chest pain	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
General disorders Death	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Gout	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Nervous system disorders Cerebrovascular accident	1.3% 2/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Nervous system disorders Cerebral infarction	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Iron deficiency anaemia	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin ulcer haemorrhage	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	1.3% 2/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Vascular disorders Peripheral ischaemia	0.64% 1/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.00% 0/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Vascular disorders Orthostatic hypotension	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Postoperative thoracic procedure complication	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	1.3% 2/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Mediastinal haemorrhage	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/156 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.	0.64% 1/157 • Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days. For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.