Trial Outcomes & Findings for Single Bolus Recombinant Nonimmunogenic Staphylokinase (Fortelyzin) and Bolus Infusion Alteplase in Patients With AIS (NCT NCT03151993)

Results Overview

The number of patients with Modified Rankin Scale (mRS) scores 0-1 on day 90 after drug administration, where 0 - No symptoms, 1 - No significant disability. All scale is 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

336 participants

Primary outcome timeframe

within 90 days after fibrinolysis

Results posted on

2025-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	Recombinant Staphylokinase Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Overall Study STARTED	168	168
Overall Study COMPLETED	168	168
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)	Total n=336 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=168 Participants	0 Participants n=168 Participants	0 Participants n=336 Participants
Age, Categorical Between 18 and 65 years	84 Participants n=168 Participants	80 Participants n=168 Participants	164 Participants n=336 Participants
Age, Categorical >=65 years	84 Participants n=168 Participants	88 Participants n=168 Participants	172 Participants n=336 Participants
Age, Continuous	64.4 years STANDARD_DEVIATION 9.6 • n=168 Participants	64.6 years STANDARD_DEVIATION 10.6 • n=168 Participants	64.5 years STANDARD_DEVIATION 10.1 • n=336 Participants
Sex: Female, Male Female	106 Participants n=168 Participants	112 Participants n=168 Participants	218 Participants n=336 Participants
Sex: Female, Male Male	62 Participants n=168 Participants	56 Participants n=168 Participants	118 Participants n=336 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Russia	168 Participants n=168 Participants	168 Participants n=168 Participants	336 Participants n=336 Participants
Baseline NIHSS score	11 score n=168 Participants	11 score n=168 Participants	11 score n=336 Participants
Baseline mRS score	4 score n=168 Participants	4 score n=168 Participants	4 score n=336 Participants

PRIMARY outcome

Timeframe: within 90 days after fibrinolysis

The number of patients with Modified Rankin Scale (mRS) scores 0-1 on day 90 after drug administration, where 0 - No symptoms, 1 - No significant disability. All scale is 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead.

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Good Functional Recovery	84 patients	68 patients

SECONDARY outcome

Timeframe: within 90 days after fibrinolysis

Composite endpoint, included the number of patients reached Modified Rankin scale 0-1 score, NIHSS 0-1 score and Barthel index 95-100. Modified Rankin scale: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead. The National Institutes of Health Stroke Scale (NIHSS): 0 - No stroke symptoms, 1-4 - Minor stroke, 5-15 - Moderate stroke, 16-20 - Moderate to severe stroke, 21-42 - Severe stroke. Barthel index: 80-100 - Independent, 60-79 - Minimally dependent, 40-59 - Partially dependent, 20-39 - Very dependent, \<20 - Totally dependent.

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
The Number of Patients With Modified Rankin Scale (0-1) + NIHSS (0-1) + Barthel (95-100)	59 patients	52 patients

SECONDARY outcome

Timeframe: after 24 hours

The median of The National Institutes of Health Stroke Scale (NIHSS) at 24 h after drug administration, where: 0 - No stroke symptoms, 1-4 - Minor stroke, 5-15 - Moderate stroke, 16-20 - Moderate to severe stroke, 21-42 - Severe stroke.

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
The Median of NIHSS After 24 Hours	6 score Interval 3.0 to 11.0	6 score Interval 3.0 to 12.0

SECONDARY outcome

Timeframe: within 90 days after fibrinolysis

The median of The National Institutes of Health Stroke Scale (NIHSS) after 90 days of drug administration, where: 0 - No stroke symptoms, 1-4 - Minor stroke, 5-15 - Moderate stroke, 16-20 - Moderate to severe stroke, 21-42 - Severe stroke.

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
The Median of NIHSS After 90 Days	2 score Interval 1.0 to 5.0	2 score Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: within 90 days after fibrinolysis

Death caused by any event

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
All Cause Death	17 patients	24 patients

SECONDARY outcome

Timeframe: within 90 days after fibrinolysis

The number of intracranial hemorrhage (events)

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Intracranial Haemorrhage	31 events	28 events

SECONDARY outcome

Timeframe: within 90 days after fibrinolysis

The number of symptomatic intracranial haemorrhage according to ECASS III definition (events). The ECASS III definition of symptomatic intracranial haemorrhage was any haemorrhage with neurologic deterioration, as indicated by an NIHSS score that was higher by 4 points or more than the value at baseline or the lowest value in the first 7 days, or any haemorrhage leading to death. In addition, the haemorrhage must have been identified as the predominant cause of the neurologic deterioration.

Outcome measures

Outcome measures
Measure	Recombinant Staphylokinase n=168 Participants Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 Participants Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Symptomatic Intracranial Haemorrhage	5 events	13 events

Adverse Events

Recombinant Staphylokinase

Serious events: 22 serious events

Other events: 7 other events

Deaths: 17 deaths

Actilyse

Serious events: 38 serious events

Other events: 8 other events

Deaths: 24 deaths

Serious adverse events

Serious adverse events
Measure	Recombinant Staphylokinase n=168 participants at risk Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 participants at risk Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Nervous system disorders Cerebral oedema	4.2% 7/168 • Number of events 7 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	8.3% 14/168 • Number of events 14 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Nervous system disorders Symptomatic intracranial haemorrhage	3.0% 5/168 • Number of events 5 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	7.7% 13/168 • Number of events 13 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Nervous system disorders Surgery	3.0% 5/168 • Number of events 5 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	1.8% 3/168 • Number of events 3 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Nervous system disorders Neurosurgery	1.2% 2/168 • Number of events 2 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	0.60% 1/168 • Number of events 1 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Cardiac disorders Acute myocardial infarction	0.60% 1/168 • Number of events 1 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	0.60% 1/168 • Number of events 1 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Blood and lymphatic system disorders Pulmonary thromboembolism	0.60% 1/168 • Number of events 1 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	1.8% 3/168 • Number of events 3 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Nervous system disorders New acute ischaemic stroke	0.60% 1/168 • Number of events 1 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	0.00% 0/168 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Gastrointestinal disorders Gastric ulcer	0.00% 0/168 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	1.2% 2/168 • Number of events 2 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.
Cardiac disorders Takotsubo cardiomyopathy	0.00% 0/168 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	0.60% 1/168 • Number of events 1 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.

Other adverse events

Other adverse events
Measure	Recombinant Staphylokinase n=168 participants at risk Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds Recombinant staphylokinase: 10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds	Actilyse n=168 participants at risk Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) Alteplase: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
Renal and urinary disorders Haematuria	4.2% 7/168 • Number of events 7 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.	4.8% 8/168 • Number of events 8 • 90 days after fibronolysis Cerebral oedema, Symptomatic intracranial haemorrhage, Surgery, Neurosurgery, Acute myocardial infarction, Pulmonary thromboembolism, New acute ischaemic stroke, Gastric ulcer, Takotsubo cardiomyopathy.

Additional Information

Dr. Eugene I. Gusev, President of the Federal Center for Brain and Neurotechnology

Federal Center for Brain and Neurotechnology

Phone: 495-280-01-74

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place