Trial Outcomes & Findings for Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency / and Sub-Study (NCT NCT03037931)

NCT ID: NCT03037931

Last Updated: 2024-07-03

Results Overview

The number of participants who died out of the total treated group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

3065 participants

Primary outcome timeframe

1 year

Results posted on

2024-07-03

Participant Flow

Participant milestones

Participant milestones
Measure	Ferric Carboxymaltose Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Overall Study STARTED	1532	1533
Overall Study COMPLETED	1123	1121
Overall Study NOT COMPLETED	409	412

Reasons for withdrawal

Reasons for withdrawal
Measure	Ferric Carboxymaltose Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Overall Study Death	354	367
Overall Study Lost to Follow-up	7	4
Overall Study Withdrawal by Subject	48	41

Baseline Characteristics

Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency / and Sub-Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ferric Carboxymaltose n=1532 Participants Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo n=1533 Participants Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution	Total n=3065 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	508 Participants n=5 Participants	525 Participants n=7 Participants	1033 Participants n=5 Participants
Age, Categorical >=65 years	1024 Participants n=5 Participants	1008 Participants n=7 Participants	2032 Participants n=5 Participants
Age, Continuous	68.57 years STANDARD_DEVIATION 10.94 • n=5 Participants	68.57 years STANDARD_DEVIATION 11.20 • n=7 Participants	68.57 years STANDARD_DEVIATION 11.07 • n=5 Participants
Sex: Female, Male Female	506 Participants n=5 Participants	531 Participants n=7 Participants	1037 Participants n=5 Participants
Sex: Female, Male Male	1026 Participants n=5 Participants	1002 Participants n=7 Participants	2028 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	85 Participants n=5 Participants	100 Participants n=7 Participants	185 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1440 Participants n=5 Participants	1424 Participants n=7 Participants	2864 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Asian	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Black or African American	162 Participants n=5 Participants	160 Participants n=7 Participants	322 Participants n=5 Participants
Race (NIH/OMB) White	1324 Participants n=5 Participants	1325 Participants n=7 Participants	2649 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment Hungary	11 participants n=5 Participants	17 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment United States	612 participants n=5 Participants	601 participants n=7 Participants	1213 participants n=5 Participants
Region of Enrollment Czechia	14 participants n=5 Participants	19 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Ukraine	243 participants n=5 Participants	217 participants n=7 Participants	460 participants n=5 Participants
Region of Enrollment Russia	58 participants n=5 Participants	65 participants n=7 Participants	123 participants n=5 Participants
Region of Enrollment New Zealand	46 participants n=5 Participants	54 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment Canada	109 participants n=5 Participants	120 participants n=7 Participants	229 participants n=5 Participants
Region of Enrollment Latvia	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Poland	83 participants n=5 Participants	87 participants n=7 Participants	170 participants n=5 Participants
Region of Enrollment Georgia	88 participants n=5 Participants	92 participants n=7 Participants	180 participants n=5 Participants
Region of Enrollment Australia	59 participants n=5 Participants	51 participants n=7 Participants	110 participants n=5 Participants
Region of Enrollment Bulgaria	195 participants n=5 Participants	197 participants n=7 Participants	392 participants n=5 Participants
Region of Enrollment Lithuania	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Estonia	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Intent-to-treat Analysis Population	1123 Participants n=5 Participants	1121 Participants n=7 Participants	2244 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Intent-to-treat Population

The number of participants who died out of the total treated group.

Outcome measures

Outcome measures
Measure	Ferric Carboxymaltose n=1532 Participants Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo n=1533 Participants Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Number of Deaths	131 Participants	158 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Intent-to-treat Population

The number of participants who were hospitalized for heart failure out of the total treated group.

Outcome measures

Outcome measures
Measure	Ferric Carboxymaltose n=1532 Participants Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo n=1533 Participants Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Number of Hospitalizations for Heart Failure	297 Participants	332 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Number of participants within the ITT population which contributed to the 6MWT data

The change in meters walked at baseline compared to 6 months later.

Outcome measures

Outcome measures
Measure	Ferric Carboxymaltose n=1285 Participants Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo n=1295 Participants Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Change in 6MWT (Six Minute Walk Test) Distance	8.179 unit of measure in meters Standard Deviation 59.963	3.979 unit of measure in meters Standard Deviation 58.896

Adverse Events

Ferric Carboxymaltose

Serious events: 413 serious events

Other events: 424 other events

Deaths: 354 deaths

Placebo

Serious events: 401 serious events

Other events: 412 other events

Deaths: 367 deaths

Serious adverse events

Other adverse events

Additional Information

Elizabeth Ernst, Global Executive Director of Regulatory Affairs

American Regent, Inc.

Phone: 631-605-5753

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Ferric Carboxymaltose n=1532 participants at risk Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo n=1533 participants at risk Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Infections and infestations Pneumonia	3.7% 57/1532 • Number of events 64 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.3% 35/1533 • Number of events 37 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations COVID-19	2.5% 39/1532 • Number of events 39 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.4% 37/1533 • Number of events 39 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Sepsis	1.4% 21/1532 • Number of events 22 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.85% 13/1533 • Number of events 14 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Cellulitis	0.78% 12/1532 • Number of events 12 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.4% 21/1533 • Number of events 27 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations COVID-19 pneumonia	0.72% 11/1532 • Number of events 11 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.1% 17/1533 • Number of events 17 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Urinary Tract Infection	1.1% 17/1532 • Number of events 20 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.59% 9/1533 • Number of events 11 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Osteomyelitis	0.46% 7/1532 • Number of events 8 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.20% 3/1533 • Number of events 3 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Influenza	0.33% 5/1532 • Number of events 5 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.26% 4/1533 • Number of events 4 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Bronchitis	0.26% 4/1532 • Number of events 4 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.26% 4/1533 • Number of events 4 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Septic shock	0.39% 6/1532 • Number of events 7 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Bacteraemia	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.26% 4/1533 • Number of events 4 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Localised infection	0.20% 3/1532 • Number of events 4 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Pyelonephritis	0.20% 3/1532 • Number of events 3 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Clostridium difficile colitis	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Diabetic foot infection	0.07% 1/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.20% 3/1533 • Number of events 5 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Urosepsis	0.26% 4/1532 • Number of events 4 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.00% 0/1533 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Appendicitis	0.07% 1/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Gastroenteritis	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Lower respiratory tract infection	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Respiratory tract infection	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 3 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Urinary tract infection bacterial	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Cystitis	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Escherichia bacteraemia	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Gangrene	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Gastroenteritis viral	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.00% 0/1533 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Herpes zoster	0.00% 0/1532 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Implant site infection	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Pneumonia aspiration	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Pneumonia bacterial	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Postoperative wound infection	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.00% 0/1533 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Respiratory syncytial virus infection	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Rhinovirus infection	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Upper respiratory tract infection	0.13% 2/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.00% 0/1533 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Wound infection	0.00% 0/1532 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.13% 2/1533 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Wound infection staphylococcal	0.07% 1/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Abdominal abscess	0.07% 1/1532 • Number of events 2 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.00% 0/1533 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Abdominal infection	0.00% 0/1532 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Abdominal wall abscess	0.07% 1/1532 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.00% 0/1533 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Abscess limb	0.00% 0/1532 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Anal abscess	0.00% 0/1532 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.07% 1/1533 • Number of events 1 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.

Other adverse events
Measure	Ferric Carboxymaltose n=1532 participants at risk Ferric Carboxymaltose 2 doses intravenously of 15mg/kg to a maximum individual dose of 750mg 7 days apart and a maximum combined dose of 1500mg - repeated every 6 months as indicated by the results of iron indices. Ferric Carboxymaltose: Intravenous Iron	Placebo n=1533 participants at risk Normal saline 15ml - 2 doses 7 days apart repeated every 6 months. Placebo: Normal Saline Solution
Infections and infestations Pneumonia	3.7% 57/1532 • Number of events 64 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.3% 35/1533 • Number of events 37 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations COVID-19	2.5% 39/1532 • Number of events 39 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.4% 37/1533 • Number of events 39 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Sepsis	1.4% 21/1532 • Number of events 22 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.85% 13/1533 • Number of events 14 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Cellulitis	0.78% 12/1532 • Number of events 12 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.4% 21/1533 • Number of events 27 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations COVID-19 pneumonia	0.72% 11/1532 • Number of events 11 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.1% 17/1533 • Number of events 17 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Infections and infestations Urinary tract infection	1.1% 17/1532 • Number of events 20 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.59% 9/1533 • Number of events 11 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Renal and urinary disorders Acute kidney injury	3.0% 46/1532 • Number of events 60 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.6% 40/1533 • Number of events 49 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Gastrointestinal disorders Gastrointestinal hemorrhage	0.85% 13/1532 • Number of events 14 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.98% 15/1533 • Number of events 17 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.5% 23/1532 • Number of events 25 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.4% 21/1533 • Number of events 27 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.0% 16/1532 • Number of events 18 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.78% 12/1533 • Number of events 13 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Metabolism and nutrition disorders Metabolism and nutrition disorders	2.9% 44/1532 • Number of events 54 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.9% 45/1533 • Number of events 60 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Nervous system disorders Nervous system disorders	2.5% 39/1532 • Number of events 46 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	3.0% 46/1533 • Number of events 55 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	2.8% 43/1532 • Number of events 54 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.3% 35/1533 • Number of events 39 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Vascular disorders Hypotension	1.1% 17/1532 • Number of events 17 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.98% 15/1533 • Number of events 18 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
General disorders General disorders and administration site conditions	1.9% 29/1532 • Number of events 34 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	2.0% 31/1533 • Number of events 34 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder	1.6% 25/1532 • Number of events 26 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.8% 27/1533 • Number of events 28 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl systs and polyps)	1.6% 25/1532 • Number of events 27 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.8% 27/1533 • Number of events 31 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Blood and lymphatic system disorders Anemia	0.46% 7/1532 • Number of events 7 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.98% 15/1533 • Number of events 15 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Hepatobiliary disorders Hepatobiliary disorders	1.1% 17/1532 • Number of events 19 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	0.72% 11/1533 • Number of events 12 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Investigations Investigations	0.59% 9/1532 • Number of events 11 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	1.1% 17/1533 • Number of events 19 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.
Cardiac disorders Cardiac disorders	3.3% 50/1532 • Number of events 56 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.	3.4% 52/1533 • Number of events 64 • 67.5 months Adverse Events (AEs) specified in the protocol were collected for duration of study (67.5 max months duration). After early/permanent discontinuation AEs were reported for 30 days after study drug. Death for any cause was part of the composite primary endpoint. All mortality (Cardiovascular and all other causes) were collected for the duration of the study (67.5 max months duration). The mortality data is used in various secondary endpoint evaluations.