Trial Outcomes & Findings for Recombinant Human Antithrombin (ATryn®) in the Treatment of Patients With DIC Associated With Severe Sepsis (NCT NCT00506519)

Last Updated: 2025-03-07

Results Overview

Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome. Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Day 28

Results posted on

2025-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	AT-150 Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control The best standard treatment for the underlying condition only Control
Overall Study STARTED	10	10	5
Overall Study Completed Treatment (Day 5)	8	7	5
Overall Study Day 28 Follow up	8	6	5
Overall Study COMPLETED	5	4	5
Overall Study NOT COMPLETED	5	6	0

Reasons for withdrawal

Reasons for withdrawal
Measure	AT-150 Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control The best standard treatment for the underlying condition only Control
Overall Study Death	4	6	0
Overall Study Adverse Event	1	0	0

Baseline Characteristics

Recombinant Human Antithrombin (ATryn®) in the Treatment of Patients With DIC Associated With Severe Sepsis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control	Total n=25 Participants Total of all reporting groups
Age, Continuous	57 years STANDARD_DEVIATION 16.6 • n=5 Participants	65.5 years STANDARD_DEVIATION 19.4 • n=7 Participants	58 years STANDARD_DEVIATION 22.9 • n=5 Participants	60.6 years STANDARD_DEVIATION 18.7 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Ethnic origin · Caucasian	8 Participants n=5 Participants	10 Participants n=7 Participants	5 Participants n=5 Participants	23 Participants n=4 Participants
Race/Ethnicity, Customized Ethnic origin · Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Weight	75.6 kg STANDARD_DEVIATION 11.3 • n=5 Participants	77.1 kg STANDARD_DEVIATION 14.5 • n=7 Participants	71.4 kg STANDARD_DEVIATION 28.2 • n=5 Participants	75.4 kg STANDARD_DEVIATION 16.2 • n=4 Participants
Height	163 cm STANDARD_DEVIATION 4.2 • n=5 Participants	169 cm STANDARD_DEVIATION 14.1 • n=7 Participants	161 cm STANDARD_DEVIATION 13.7 • n=5 Participants	165 cm STANDARD_DEVIATION 11.1 • n=4 Participants

PRIMARY outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.	2 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Mortality at Day 28	1 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 90

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Mortality at Day 90	4 Participants	6 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Day 6

Population: Participants alive on day 6.

Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.

Outcome measures

Outcome measures
Measure	AT-150 n=9 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=7 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6	-0.2 score on a scale Standard Deviation 1.2	-0.3 score on a scale Standard Deviation 1.5	0.2 score on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline to Day 6

Population: Participants alive on day 6.

Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome

Outcome measures

Outcome measures
Measure	AT-150 n=9 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=7 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6	-3.0 score on a scale Standard Deviation 1.7	-2.2 score on a scale Standard Deviation 2.4	-3.0 score on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: Baseline to Day 28

Days alive and out of ICU at day 28 for all patients

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Days Alive and Out of ICU Day 28	9.8 Days Standard Deviation 10.8	4.7 Days Standard Deviation 10.0	13.6 Days Standard Deviation 8.4

SECONDARY outcome

Timeframe: Baseline to Day 28

Days alive and out of Hospital at day 28 for all patients

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Days Alive and Out of Hospital Day 28	3.0 Days Standard Deviation 6.4	3.0 Days Standard Deviation 6.6	4.6 Days Standard Deviation 7.4

SECONDARY outcome

Timeframe: Baseline to Day 28

Days alive and free of inotrope/vasopressor at day 28 for all patients

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Days Alive and Free of Inotrope/Vasopressor Support Day 28	20.7 Days Standard Deviation 9.0	12.4 Days Standard Deviation 11.7	21.6 Days Standard Deviation 6.8

SECONDARY outcome

Timeframe: Baseline to Day 28

Days alive and free of mechanical ventilation at day 28 for all patients

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Days Alive and Off Ventilator Day 28	11.4 Days Standard Deviation 10.5	8.9 Days Standard Deviation 11.8	14.4 Days Standard Deviation 8.8

SECONDARY outcome

Timeframe: Baseline to Day 28

Days alive and out of renal replacement therapy at day 28 for all patients

Outcome measures

Outcome measures
Measure	AT-150 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Days Alive and Free of Need for Renal Replacement Therapy Day 28	22.6 Days Standard Deviation 13.3	10.5 Days Standard Deviation 13.4	23.0 Days Standard Deviation 6.9

SECONDARY outcome

Timeframe: Baseline to Day 6

Population: Participants alive on day 6 who gave a sample.

Outcome measures

Outcome measures
Measure	AT-150 n=9 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=6 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Change From Baseline to Day 6 in Inflammation Marker IL-6	-68429 pg/mL Standard Deviation 192828	-13153 pg/mL Standard Deviation 31801	-69651 pg/mL Standard Deviation 141889

SECONDARY outcome

Timeframe: Baseline to Day 6

Population: Participants alive on day 6 who gave a sample.

Outcome measures

Outcome measures
Measure	AT-150 n=9 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=6 Participants Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 Participants The best standard treatment for the underlying condition only Control
Change From Baseline to Day 6 in Inflammation Marker Procalcitonin	-203.8 ng/mL Standard Deviation 340.2	-51.1 ng/mL Standard Deviation 49.6	-139.6 ng/mL Standard Deviation 146.2

Adverse Events

AT-150

Serious events: 5 serious events

Other events: 10 other events

Deaths: 4 deaths

AT-250

Serious events: 8 serious events

Other events: 10 other events

Deaths: 6 deaths

Control

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Disclosure

LEO Pharma A/S

Phone: +45 44 94 58 88

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee LEO Pharma A/S seeks publication of all clinical trials in peer-reviewed journals regardless of whether the findings are positive or negative, and acknowledges the investigators' right to publish results irrespective of outcome. Investigators are permitted to publish their individual data with the prior review and consent of LEO Pharma A/S
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	AT-150 n=10 participants at risk Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 participants at risk Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 participants at risk The best standard treatment for the underlying condition only Control
Respiratory, thoracic and mediastinal disorders Haemoptysis	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Hepatobiliary disorders Portal vein thrombosis	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Vascular disorders Shock haemorrhagic	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Vascular disorders Haemorrhage	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	30.0% 3/10 • Number of events 8 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	40.0% 2/5 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Myocardial infarction	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Puncture site haemorrhage	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	60.0% 3/5 • Number of events 3 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Blood and lymphatic system disorders Tracheal haemorrhage	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	30.0% 3/10 • Number of events 3 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Nervous system disorders Cerebral infarction	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Respiratory, thoracic and mediastinal disorders Pleural haemorrhage	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Injury, poisoning and procedural complications Operative haemorrhage	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Blood and lymphatic system disorders Haematoma	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Blood and lymphatic system disorders Gingival bleeding	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Blood and lymphatic system disorders Rectal haemorrhage	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Injury, poisoning and procedural complications Tooth injury	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Injury, poisoning and procedural complications Wound	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Necrosis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Catheter site discharge	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Catheter site haemorrhage	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.

Other adverse events
Measure	AT-150 n=10 participants at risk Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	AT-250 n=10 participants at risk Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	Control n=5 participants at risk The best standard treatment for the underlying condition only Control
Blood and lymphatic system disorders Anaemia	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	40.0% 4/10 • Number of events 5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Blood and lymphatic system disorders Thrombocytopenia	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	60.0% 3/5 • Number of events 3 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Arrhythmia	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Atrial fibrillation	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Cardiac failure	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Cardiomyopathy	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Cyanosis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Tachyarrhythmia	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Tachycardia	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Cardiac disorders Ventricular bigeminy	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Ascites	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Gastric perforation	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Large intestine perforation	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Nausea	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Peritonitis	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Gastrointestinal disorders Vomiting	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 3 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Hyperthermia	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Malaise	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Multi-organ failure	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Oedema	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	40.0% 2/5 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Oedema peripheral	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
General disorders Systemic inflammatory response syndrome	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Hepatobiliary disorders Biloma	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Hepatobiliary disorders Cholestasis	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Hepatobiliary disorders Cytolytic hepatitis	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Immune system disorders Acquired hypogammaglobulinaemia	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Candidiasis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Endocarditis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Infection	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Myocarditis septic	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Pneumonia	30.0% 3/10 • Number of events 4 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 2/10 • Number of events 2 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Sepsis	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Infections and infestations Septic shock	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Injury, poisoning and procedural complications Blister	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Injury, poisoning and procedural complications Eschar	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	10.0% 1/10 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/5 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Investigations Blood lactic acid increased	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Investigations Vitamin K decreased	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	0.00% 0/10 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.	20.0% 1/5 • Number of events 1 • 90 days In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'. All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.