Trial Outcomes & Findings for Multi-arm Optimization of Stroke Thrombolysis (NCT NCT03735979)

Last Updated: 2025-02-07

Results Overview

The modified Rankin scale is a 7 point ordinal scale ranging from 0="no symptoms" to 6="death" . For the primary analysis, the scale was analyzed with patient-centered utility weights. We assigned the following utility weights to the seven levels: 10, 9.1,, 7.6, 6.5, 3.3, 0, 0 (with higher scores indicating a better outcome).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

514 participants

Primary outcome timeframe

90 days after randomization

Results posted on

2025-02-07

Participant Flow

Participant milestones

Participant milestones
Measure	Argatroban 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo Placebo: IV placebo solution
Overall Study STARTED	59	227	228
Overall Study COMPLETED	56	210	212
Overall Study NOT COMPLETED	3	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Argatroban 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo Placebo: IV placebo solution
Overall Study Lost to Follow-up	1	12	14
Overall Study Withdrawal by Subject	1	5	2
Overall Study Not due to the above reasons	1	0	0

Baseline Characteristics

Multi-arm Optimization of Stroke Thrombolysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution	Total n=514 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	68 years n=7 Participants	66 years n=5 Participants	67 years n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	118 Participants n=7 Participants	110 Participants n=5 Participants	256 Participants n=4 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	109 Participants n=7 Participants	118 Participants n=5 Participants	258 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	23 Participants n=7 Participants	14 Participants n=5 Participants	40 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants	203 Participants n=7 Participants	213 Participants n=5 Participants	472 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	61 Participants n=7 Participants	53 Participants n=5 Participants	129 Participants n=4 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants	156 Participants n=7 Participants	170 Participants n=5 Participants	367 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
NIHSS	12 units on a scale n=5 Participants	12 units on a scale n=7 Participants	11 units on a scale n=5 Participants	12 units on a scale n=4 Participants
IV Thrombolytic recombinant tissue plasminogen activator (rt-PA)	52 Participants n=5 Participants	157 Participants n=7 Participants	151 Participants n=5 Participants	360 Participants n=4 Participants
IV Thrombolytic tenecteplase (TNK)	7 Participants n=5 Participants	70 Participants n=7 Participants	77 Participants n=5 Participants	154 Participants n=4 Participants
Stroke Onset to IV Thrombolytic Start	100 minutes STANDARD_DEVIATION 38.5 • n=5 Participants	103 minutes STANDARD_DEVIATION 36 • n=7 Participants	101 minutes STANDARD_DEVIATION 36.1 • n=5 Participants	102 minutes STANDARD_DEVIATION 36.3 • n=4 Participants
IV Thrombolytic Start to Study Drug Bolus	62 minutes STANDARD_DEVIATION 14.3 • n=5 Participants	65 minutes STANDARD_DEVIATION 20.5 • n=7 Participants	63 minutes STANDARD_DEVIATION 18.2 • n=5 Participants	64 minutes STANDARD_DEVIATION 18.9 • n=4 Participants
Endovascular Thrombectomy (EVT) received	27 Participants n=5 Participants	99 Participants n=7 Participants	99 Participants n=5 Participants	225 Participants n=4 Participants

PRIMARY outcome

Timeframe: 90 days after randomization

Population: Intention-to-treat

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
90-day Utility Weighted Modified Rankin Scores (UW-mRS)	5.2 score on a scale Standard Deviation 3.7	6.3 score on a scale Standard Deviation 3.2	6.8 score on a scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: 24 hours after randomization

National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit. This is a dichotomous analysis with a cutpoint of 0,1,2 defining the event.

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
Percentage of Participants With NIHSS Less Than or Equal to 2 at 24 Hours	14 Participants	84 Participants	89 Participants

SECONDARY outcome

Timeframe: 24 hours after randomization

National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit.

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
Change From Baseline to 24-hour NIHSS	-5.1 units on a scale Standard Deviation 9.3	-6.1 units on a scale Standard Deviation 8.4	-6.3 units on a scale Standard Deviation 6.8

SECONDARY outcome

Timeframe: 90 days after randomization

Population: Intention-to-treat sample

The modified Rankin scale (mRS) is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes. For patients with a pre-stroke mRS of greater than 0 or 1, these patients had to return to their historical (pre-stroke) value to be counted as a success.

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
Percentage of Participants With 90-day mRS 0 or 1 (or Return to Their Historical mRS)	14 Participants	82 Participants	92 Participants

SECONDARY outcome

Timeframe: 90 days after randomization

Population: Intention-to-treat

modified Rankin scale is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes.

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
Percentage of Participants With 90-day mRS 0, 1 or 2 (or Return to Their Historical mRS)	26 Participants	126 Participants	139 Participants

SECONDARY outcome

Timeframe: 90 days after randomization

Population: Intention-to-treat

modified Rankin scale is a 7 point ordinal scale ranging from 0="no symptoms at all" to 6="death" where lower scores are better outcomes.

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
90-day mRS	3 units on a scale Interval 2.0 to 5.0	2 units on a scale Interval 1.0 to 3.0	2 units on a scale Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 90 days after randomization

EuroQol Five-Dimension (EQ-5D) is a measure of health-related quality of life ranging from -0.59 to 1 where 1 is the best possible health state.

Outcome measures

Outcome measures
Measure	Argatroban n=59 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 Participants Placebo: IV placebo solution
90-day EQ-5D	0.6 score on a scale Standard Deviation 0.3	0.6 score on a scale Standard Deviation 0.4	0.7 score on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: baseline

Population: Only participants that received endovascular thrombectomy are analyzed for this outcome.

The modified thrombolysis in cerebral infarction (TICI) score prior to endovascular thrombectomy procedure. The modified pre-thrombectomy TICI score is a 4 point scale with possible values of 0, 1, 2A, and 2B. The values are defined as follows: 0=No flow, 1=Penetration without distal branch filling, 2A=\<50% partial reperfusion, and 2B=50%-99% partial reperfusion.

Outcome measures

Outcome measures
Measure	Argatroban n=27 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=99 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=99 Participants Placebo: IV placebo solution
Pre-thrombectomy Modified TICI Score of 2B.	2 Participants	5 Participants	6 Participants

SECONDARY outcome

Timeframe: baseline

Population: Only participants that received endovascular thrombectomy are analyzed for this outcome.

The modified thrombolysis in cerebral infarction (TICI) score prior to endovascular thrombectomy procedure. The modified post-thrombectomy TICI score is a 5 point scale with possible values of 0, 1, 2A, 2B, 3. The values are defined as follows: 0=No flow, 1=Penetration without distal branch filling, 2A=\<50% partial reperfusion, 2B=50%-99% partial reperfusion, and 3=Completed reperfusion

Outcome measures

Outcome measures
Measure	Argatroban n=27 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=99 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=99 Participants Placebo: IV placebo solution
Post-thrombectomy Modified TICI Score of 2B or 3	22 Participants	92 Participants	93 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 hours after randomization

Population: Participants that took any amount of study drug (safety sample)

Type 2 parenchymal hemorrhage or a parenchymal hemorrhage remote from the area of infarction with neurologic deterioration (defined as an increase of ≥4 points in the NIHSS score)within 36 hours after randomization.

Outcome measures

Outcome measures
Measure	Argatroban n=54 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=212 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=217 Participants Placebo: IV placebo solution
Symptomatic Intracranial Hemorrhage Within 36 Hours (Primary Safety Outcome)	2 Participants	7 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 hours after randomization

Population: Participants that took any amount of study drug (safety sample).

Outcome measures

Outcome measures
Measure	Argatroban n=54 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=212 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=217 Participants Placebo: IV placebo solution
Type 1 or Type 2 Parenchymal Hemorrhage Within 36 Hours (Safety Outcome)	3 Participants	18 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 hours after randomization

Population: Participants that took any amount of study drug (safety sample).

Symptomatic or asymptomatic intracranial hemorrhage within 36 hours of randomization.

Outcome measures

Outcome measures
Measure	Argatroban n=54 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=212 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=217 Participants Placebo: IV placebo solution
Any Intracranial Hemorrhage Within 36 Hours (Safety Outcome)	20 Participants	51 Participants	51 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days after randomization

Population: Participants that took any amount of study drug (safety sample).

Other major hemorrhage other than intracranial hemorrhage (resulting in the transfusion of \>2 units of packed red cells).

Outcome measures

Outcome measures
Measure	Argatroban n=54 Participants 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=212 Participants 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=217 Participants Placebo: IV placebo solution
Other Major Hemorrhage Other Than Intracranial Hemorrhage Within 7 Days (Safety Outcome)	1 Participants	2 Participants	3 Participants

Adverse Events

Argatroban

Serious events: 26 serious events

Other events: 12 other events

Deaths: 13 deaths

Eptifibatide

Serious events: 85 serious events

Other events: 42 other events

Deaths: 25 deaths

Placebo

Serious events: 78 serious events

Other events: 33 other events

Deaths: 17 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Argatroban n=59 participants at risk 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 participants at risk 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 participants at risk Placebo: IV placebo solution
Blood and lymphatic system disorders Anaemia	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/227 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/228 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Cardiac disorders Atrial fibrillation	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/227 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/228 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Infections and infestations Urinary tract infection	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Infections and infestations Coronavirus test positive	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/228 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/227 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.00% 0/228 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Cerebral haemorrhage	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	4.4% 10/227 • Number of events 10 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.8% 4/228 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Haemorrhage intracranial	3.4% 2/59 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Haemorrhagic transformation stroke	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/228 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Headache	1.7% 1/59 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/228 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Vascular disorders Haematoma	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	3.1% 7/227 • Number of events 8 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.8% 4/228 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Vascular disorders Hypotension	5.1% 3/59 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).

Additional Information

Jordan J. Elm, PhD

Medical University of South Carolina

Phone: 843-876-1605

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Argatroban n=59 participants at risk 100µg/kg bolus followed by 3µg/kg per minute for 12 hours	Eptifibatide n=227 participants at risk 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours	Placebo n=228 participants at risk Placebo: IV placebo solution
Cardiac disorders Acute myocardial infarction	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/227 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/228 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Cardiac disorders Atrial fibrillation	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/228 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Cardiac disorders Cardiac arrest	5.1% 3/59 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.6% 6/227 • Number of events 6 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Gastrointestinal disorders Dysphagia	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.8% 4/228 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Gastrointestinal disorders Gastrointestinal haemorrhage	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/227 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/228 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
General disorders Chest pain	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Infections and infestations Corona virus infection	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.8% 4/227 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/228 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Infections and infestations Urinary tract infection	1.7% 1/59 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/227 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/228 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Brain oedema	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.8% 4/227 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/228 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Cerebrovascular accident	1.7% 1/59 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/228 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Haemorrhage intracranial	3.4% 2/59 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	3.1% 7/227 • Number of events 7 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/228 • Number of events 6 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Haemorrhagic transformation stroke	0.00% 0/59 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.6% 6/228 • Number of events 6 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Ischaemic stroke	8.5% 5/59 • Number of events 6 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	3.1% 7/227 • Number of events 8 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.6% 6/228 • Number of events 7 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Nervous system disorders Stroke in evolution	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/227 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.44% 1/228 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Renal and urinary disorders Acute kidney injury	3.4% 2/59 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	1.3% 3/227 • Number of events 3 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.7% 1/59 • Number of events 1 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.00% 0/227 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	2.2% 5/228 • Number of events 5 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.8% 4/59 • Number of events 4 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	3.1% 7/227 • Number of events 7 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	0.88% 2/228 • Number of events 2 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).
General disorders Low frequency SAEs	27.1% 16/59 • Number of events 21 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	23.8% 54/227 • Number of events 83 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).	22.8% 52/228 • Number of events 67 • 90 days after randomization For all-cause mortality, the at-risk population is participants that received any amount of study drug (safety sample). For serious and other adverse events, the at-risk population is all randomized participants (intent to treat sample).