Single Bolus Non-immunogenic Staphylokinase in Patients With Acute Ischemic Stroke Within 4.5-24 Hours of Symptom Onset

NCT ID: NCT07324837

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

990 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-01

Study Completion Date

2029-01-01

Brief Summary

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Multicenter, double-blind, randomized, placebo-controlled phase III clinical trial. At the clinical sites, patients with acute ischemic stroke within 4.5-24 hours of symptom onset will be randomized to receive a single bolus injection of the recombinant non-immunogenic staphylokinase (Fortelyzin®, LLC "SuperGene", Russia) or placebo.

Detailed Description

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The current guidelines recommended intravenous thrombolysis as the first-line treatment for acute large vessel occlusion of anterior circulation stroke within 4.5 hours of stroke onset. However, a majority of patients arrive in the hospital outside the 4.5-hour time window, who could not receive intravenous thrombolysis.

In 2020, the non-immunogenic staphylokinase was registered in Russia for the acute ischemic stroke treatment within 4,5 h after the onset of symptoms. In the FRIDA randomized clinical trial the non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Non-immunogenic staphylokinase is easy to administer with a rapid single bolus of 10 mg regardless patients' bodyweight, simplifying clinical use. In 2024, the non-immunogenic staphylokinase has been included in the updated Russian clinical guidelines for the acute ischemic stroke treatment.

A rapid (10 s) single bolus of the non-immunogenic staphylokinase in patients with acute ischemic stroke may provide significant advantages over a one-hour alteplase administration in the more rapid reperfusion in the first 24 hours after thrombolysis and a greater number of good functional outcomes. It can be assumed that the non-immunogenic staphylokinase usage in patients with acute ischemic stroke outside the 4.5-hour therapeutic window will lead to the restoration of collateral blood flow in the penumbra in comparison with standard medical management.

Therefore, FRIDA-CT trial is aimed to investigate the efficacy and safety of the non-immunogenic staphylokinase within the time window of 4.5-24 hours, wake-up stroke or no witness stroke in patients who had an acute ischaemic stroke with salvageable tissue due to large vessel occlusion.

In the multicenter, double-blind, randomized, placebo-controlled phase III clinical trial patients who had an acute ischaemic stroke due to anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume \<70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) will be included and randomised to the non-immunogenic staphylokinase, 10 mg (single bolus) regardless patient's bodyweight or placebo group. Patients who are intended for direct thrombectomy will be excluded from the trial. Follow-up period will be 90 days.

Conditions

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Ischemic Stroke, Acute

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Non-immunogenic staphylokinase

The non-immunogenic staphylokinase is given as a single intravenous bolus, 10 mg (within 5-10 seconds) immediately upon randomization regardless patient's bodyweight

Group Type EXPERIMENTAL

non-immunogenic staphylokinase

Intervention Type DRUG

The non-immunogenic staphylokinase is given as a single intravenous bolus, 10 mg (within 5-10 seconds) immediately upon randomization regardless patient's bodyweight

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo is given as a single intravenous bolus (within 5-10 seconds) immediately upon randomization

Interventions

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non-immunogenic staphylokinase

The non-immunogenic staphylokinase is given as a single intravenous bolus, 10 mg (within 5-10 seconds) immediately upon randomization regardless patient's bodyweight

Intervention Type DRUG

Placebo

Placebo is given as a single intravenous bolus (within 5-10 seconds) immediately upon randomization

Intervention Type DRUG

Other Intervention Names

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Fortelyzin®

Eligibility Criteria

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Inclusion Criteria

1. Men and women aged 18 years and over;
2. Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrolment, including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
3. Pre-stroke modified Rankin scale (mRS) score≤1;
4. Internal carotid artery, middle cerebral artery M1 or M2 occlusion confirmed by CT/MRI, internal carotid artery, middle cerebral artery M1 or M2 being responsible for signs and symptoms of acute ischemic stroke;
5. Neuroimaging: target mismatch profile on CT or MRI perfusion: ischemic core volume \<70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL;
6. Alberta Stroke Program Early CT score (ASPECTS) \> 6;
7. Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive);
8. The patient is not planned or cannot undergo thrombectomy or intravenous thrombolysis in accordance with the current version of the Clinical Guidelines;
9. Written informed consent from patients or their legally authorized representatives.

Exclusion Criteria

1. Acute ischemic stroke within 4,5 h after symptom onset;
2. Intended to proceed to endovascular treatment;
3. Known hypersensitivity to the non-immunogenic staphylokinase;
4. Convulsive seizures at the onset of the disease, if there is no certainty that the seizure is a clinical manifestation of acute ischemic stroke;
5. Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), and the inability to reduce systolic blood pressure below 180 mmHg or diastolic blood pressure below 105 mmHg;
6. Blood glucose \<2.8 or \>22.2 mmol/L (after blood glucose level correction to the specified values, inclusion of the patient in the study is possible);
7. Neuroimaging (CT, MRI) signs of intracranial hemorrhage, brain tumor, arteriovenous malformation, brain abscess, cerebral aneurysm;
8. Subarachnoid hemorrhage;
9. Major bleeding currently or within the past 6 months;
10. Surgery on the brain or spinal cord in the last 2 months;
11. Punctures of non-compressible arteries and veins in the last 7 days;
12. Gastrointestinal or genitourinary bleeding in the last 3 weeks. Confirmed exacerbations of gastric ulcer and duodenal ulcer in the last 3 months;
13. Platelet count below 100,000/mm3;
14. Previous stroke or severe traumatic brain injury within 3 months;
15. Unable to perform CT or MRI;
16. History of hemorrhagic stroke or stroke of unspecified genesis;
17. Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion);
18. Concomitant use of indirect oral anticoagulants (warfarin) with INR \> 1.7;
19. Taking direct anticoagulants (heparin, heparinoids) in the previous 48 hours with an APTT value above normal;
20. Taking new oral anticoagulants in the previous 48 hours with a thrombin time value above normal and the impossibility of administering the specific antagonist idarucizumab (for dabigatran) or the presence of anti-Xa activity (for rivaroxaban, apixaban and edoxaban).
21. Severe liver disease, including liver failure, liver cirrhosis, portal hypertension (with esophageal varices), active hepatitis;
22. Acute pancreatitis;
23. Bacterial endocarditis, pericarditis;
24. Arterial aneurysms, malformations of arteries and veins. Suspected dissecting aortic aneurysm;
25. Cancer with an increased risk of bleeding;
26. Major surgeries or severe injuries within the last 14 days, minor surgeries or invasive procedures within the last 10 days;
27. Prolonged or traumatic cardiopulmonary resuscitation (more than 2 minutes);
28. Hemorrhagic diathesis, including renal and hepatic failure;
29. Data on bleeding or acute trauma (fracture) at the time of examination;
30. Pregnant women, nursing mothers, or reluctant to use effective contraceptive measures during the period of trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Supergene, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nikolay A. Shamalov, MD, prof

Role: PRINCIPAL_INVESTIGATOR

Federal Center for Brain and Neurotechnology of the Federal Medical and Biological Agency of Russia

Sergey S. Markin, MD, prof

Role: STUDY_DIRECTOR

LLC "SuperGene"

Locations

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Ryazan Regional Clinical Hospital

Ryazan, Ryazan Oblast, Russia

Site Status

Altai Regional Clinical Hospital

Barnaul, , Russia

Site Status

Chelyabinsk Regional Clinical Hospital No. 3

Chelyabinsk, , Russia

Site Status

Irkutsk Regional Clinical Hospital

Irkutsk, , Russia

Site Status

Kaluga Regional Clinical Hospital

Kaluga, , Russia

Site Status

Interregional Clinical and Diagnostic Center

Kazan', , Russia

Site Status

S.V. Ochapovsky Research Institute - Regional Clinical Hospital No. 1

Krasnodar, , Russia

Site Status

N.I. Pirogov Russian National Research Medical University

Moscow, , Russia

Site Status

V.I. Voynov Orenburg Regional Clinical Hospital

Orenburg, , Russia

Site Status

Leningradskaya Regional Clinical Hospital

Saint Petersburg, , Russia

Site Status

Sergiev Posad District Hospital

Sergiyev Posad, , Russia

Site Status

Tver Regional Clinical Hospital

Tver', , Russia

Site Status

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, , Russia

Site Status

City Clinical Hospital of Emergency Medical Care No. 25

Volgograd, , Russia

Site Status

Sverdlovsk Regional Clinical Hospital No. 1

Yekaterinburg, , Russia

Site Status

Countries

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Russia

Central Contacts

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Nikolay A. Shamalov, MD, prof

Role: CONTACT

(499) 936-99-37 ext. +7

Natalya A. Marskaya

Role: CONTACT

(499) 936-99-37 ext. +7

Facility Contacts

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Sergei B. Aksentyev, PhD

Role: primary

Sergey A. Fedyanin, PhD

Role: primary

(3852) 68-97-41 ext. +7

Dmitry V. Popov, PhD

Role: primary

Ivan V. Korobeynikov, PhD

Role: primary

Ulukpan A. Elemanov, PhD

Role: primary

(484) 240-33-03 ext. +7

Dina R. Khasanova, MD, Prof

Role: primary

Ludmila V. Timchenko, MD, prof

Role: primary

Larisa L. Korsunskaya, MD, Prof

Role: primary

Alexandr N. Chirkov, PhD

Role: primary

Natalya V. Zhukovskaya, MD, prof

Role: primary

Anton G. Koledinsky, MD, PhD

Role: primary

(496) 542-22-84 ext. +7

Ksenia V. Khoroshavina

Role: primary

(482) 277-54-65 ext. +7

Eduard A. Ponomarev, MD, prof

Role: primary

Andrey M. Alasheev, MD, prof

Role: primary

References

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Gusev EI, Martynov MY, Nikonov AA, Shamalov NA, Semenov MP, Gerasimets EA, Yarovaya EB, Semenov AM, Archakov AI, Markin SS; FRIDA Study Group. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4.5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurol. 2021 Sep;20(9):721-728. doi: 10.1016/S1474-4422(21)00210-6.

Reference Type RESULT
PMID: 34418399 (View on PubMed)

Shamalov NA, Martynov MY, Yarovaya EB, Chefranova ZY, Kutsenko VA, Semenov AM, Ivanov SV, Semenov MP, Markin SS, Gusev EI; FORPI study group. Thrombolysis With the Nonimmunogenic Staphylokinase for Acute Ischemic Stroke in FORPI Registry: An Observational Study. Stroke. 2025 Nov 26. doi: 10.1161/STROKEAHA.125.051115. Online ahead of print.

Reference Type RESULT
PMID: 41293810 (View on PubMed)

Other Identifiers

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FRIDA-CT

Identifier Type: -

Identifier Source: org_study_id

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