Post-registration Trial of the Non-immunogenic Staphylokinase in Acute Ischemic Stroke (FORPI Registry)

An Open, Prospective, Non-interventional, Multicentre, Controlled Study of Safety and Efficacy of the Thrombolysis With the Non-immunogenic Staphylokinase in Patients With Acute Ischemic Stroke (FORPI Registry)

The aim of FORPI Registry is to study the safety and efficacy of the non-immunogenic staphylokinase in patients with acute ischemic stroke in routine clinical practice.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Non-immunogenic staphylokinase

Detailed Description

Acute ischemic stroke is caused by the formation of blood clot in the major vessel which gives blood supply to a certain part of the brain. New approaches to the treatment of acute ischemic stroke include the use of modern highly effective methods of reperfusion of brain tissue in the first hours of the disease, aimed at restoring blood flow in the affected vessel, which helps prevent the development of irreversible damage to brain tissue or reduce its volume, i.e. minimize the severity of residual neurological deficit.

In December 2019, a multicenter, open-label, randomized non-inferiority trial of the efficacy and safety of the non-immunogenic staphylokinase (Fortelyzin®) compared with alteplase (Actilyse®) in patients with acute ischemic stroke (FRIDA) was completed (NCT03151993).

The primary efficacy outcome in both the non-immunogenic staphylokinase and alteplase groups, as well as in their subgroups depending on age, body weight, onset to treatment time, baseline NIHSS, localization and subtype of acute ischemic stroke showed that the non-immunogenic staphylokinase administered as a single bolus in a dose of 10 mg regardless of body weight is non-inferior to alteplase, administered as a bolus infusion at a dose of 0.9 mg/kg body weight, at a maximum dose of 90 mg in the treatment of patients with acute ischemic stroke within 4.5 hours from the symptoms onset. The non-immunogenic staphylokinase has demonstrated high safety profile. The indication "acute ischemic stroke" is included in the Instructions for medical use of the non-immunogenic staphylokinase. In routine clinical practice, the non-immunogenic staphylokinase is used for acute ischemic stroke treatment since 2021.

The aim of FORPI Registry is to study the safety and efficacy of the non-immunogenic staphylokinase in patients with acute ischemic stroke in routine clinical practice.

• Study Type: Observational
• Enrollment (Actual): 23250

Contacts and Locations

Study Locations

• Russia
  • Moscow, Russia, 117513
    • Federal Brain and Neurotechnology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Men and women aged 18 years and older with verified acute ischemic stroke, less than 4.5 h symptoms onset to treatment, who received a single intravenous bolus of the non-immunogenic staphylokinase (10 mg).

Description

Inclusion Criteria:

• Men and women aged 18 years and older.
• Verified diagnosis of acute ischemic stroke.
• The time from the symptoms onset is no more than 4.5 hours.
• Thrombolysis with the non-immunogenic staphylokinase, 10 mg as a single intravenous bolus.

Exclusion Criteria:

• The time from the symptoms onset is more than 4.5 hours or the time of the symptoms onset is unknown.
• Increased sensitivity to the non-immunogenic staphylokinase.
• Systolic blood pressure above 185 mm Hg or diastolic blood pressure above 110 mm Hg or the need in the drug administration to reduce blood pressure to these levels.
• Neuroimaging (CT, MRI) signs of intracranial hemorrhage, brain tumors, arteriovenous malformation, brain abscess, aneurysm of cerebral vessels.
• Surgery on the brain or spinal cord.
• Suspicion of subarachnoid hemorrhage.
• Signs of severe stroke: clinical signs (stroke scale NIH > 25), neuroimaging (according to CT of the brain and / or MRI of the brain in the DWI, the ischemia focuses on the territory of more than 1/3 of the CMA pool).
• Simultaneous reception of oral anticoagulants, for example, warfarin with INR> 1.3.
• The use of direct anticoagulants (heparin, heparinoids) in the preceding stroke of 48 h with APTT values above the norm.
• Prior stroke or severe head injury within 3 months.
• Significant regression of neurological symptoms during the observation of the patient before thrombolysis.
• Hemorrhagic stroke or stroke, unspecified in history.
• Strokes of any genesis in the history of a patient with diabetes mellitus.
• Gastrointestinal bleeding or bleeding from the genitourinary system in the last 3 weeks. Confirmed exacerbations of gastric ulcer and duodenal ulcer during the last 3 months.
• Extensive bleeding now or within the previous 6 months.
• Severe liver disease, including liver failure, cirrhosis, portal hypertension (with varicose veins of the esophagus), active hepatitis.
• Acute pancreatitis.
• Bacterial endocarditis, pericarditis.
• Aneurysms of arteries, malformations of arteries and veins. Suspicion of exfoliating aortic aneurysm.
• Neoplasms with an increased risk of bleeding.
• Large operations or severe injuries within the last 14 days, minor surgery or invasive manipulation in the last 10 days.
• Puncture of uncompensated arteries and veins during the last 7 days.
• Prolonged or traumatic cardiopulmonary resuscitation (more than 2 min).
• Pregnancy, obstetrics, 10 days after birth.
• The number of platelets is less than 100,000 / μL.
• Blood glucose less than 2.7 mmol / L or more than 22.0 mmol / L.
• Hemorrhagic diathesis, including renal and hepatic insufficiency.
• Data on bleeding or acute trauma (fracture) at the time of examination.
• Seizures in the onset of the disease, if there is no certainty that the seizure is a clinical manifestation of acute ischemic stroke with a postictal residual deficiency.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non-immunogenic staphylokinase; Drug: non-immunogenic staphylokinase	Drug: Non-immunogenic staphylokinase; Drug: non-immunogenic staphylokinase 10 mg as a single intravenous bolus Other Names: Fortelyzin®; Other Names: Fortelyzin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) score of 0-2 on day 90 after drug administration	The number of patients with Modified Rankin Scale (mRS) scores 0-2 on day 90 after drug administration, where 0 - No symptoms, 1 - No significant disability, 2 - Slight disability.	day 90 after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS score on day 90 after drug administration	The median of mRS score on day 90 after drug administration, where: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead.	day 90 after drug administration
The National Institutes of Health Stroke Scale (NIHSS) at 24 hours after drug administration	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.	24 hours after drug administration
NIHSS on day 7 after drug administration	The median of NIHSS on discharge	day 7 after drug administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	The number of death from any causes during 90 days after drug administration	day 90 after drug administration
Intracranial haemorrhage	The number of intracranial haemorrhage during 90 days after drug administration	day 90 after drug administration
Symptomatic intracerebral haemorrhage	The number of symptomatic intracranial haemorrhage (sICH) defined as an NIHSS decline of ≥4 points compared with baseline NIHSS or the lowest NIHSS value or death between baseline and 7 days, associated with any haemorrhage judged by core lab evaluation to be responsible for the decline. Blood may be anywhere in the intracranial space including in the intraventricular, intraparenchymal and/or subarachnoid space (modified ECASS III definition) during 90 days after drug administration	day 90 after drug administration
Major bleedings	The number of major bleedings (according to BARC classification type 3 and 5) during 90 days after drug administration	day 90 after drug administration
Thrombectomy	The number of thrombectomy during 90 days after drug administration	day 90 after drug administration
Allergic reactions	The number of allergic reactions during 90 days after drug administration	day 90 after drug administration
Pulmonary embolism	The number of pulmonary embolism during 90 days after drug administration	day 90 after drug administration

Collaborators and Investigators

• Sponsor: Supergene, LLC
• Collaborators: Federal Center of Cerebrovascular Pathology and Stroke, Russian Federation Ministry of Health
• Investigators: Principal Investigator: Nikolay A. Shamalov, MD, PhD Prof, Federal Brain and Neurotechnology Center

Publications and helpful links

General Publications

• 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.
• Alasheev AM, Lantsova EV, Tretyakov DA. [Efficacy and safety of non-immunogenic staphylokinase in the ischemic stroke in real-world clinical practice in the Sverdlovsk region]. Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(7):74-79. doi: 10.17116/jnevro202312307174. Russian.
• Ramazanov GR, Kokov LS, Shamalov NA, Kovaleva EA, Klychnikova EV, Akhmatkhanova LK, Cheboksarov DV, Khamidova LT, Muslimov RS, Rybalko NV, Petrikov SS. [First case of thrombolysis with non-immunogenic staphylokinase in a patient with ischemic stroke receiving dabigatran etexilate followed by thrombectomy]. Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122(6):145-151. doi: 10.17116/jnevro2022122061145. Russian.
• Kulesh AA, Syromyatnikova LI, Krapivin S, Astanin PV. [Comparison of the effectiveness of non-immunogenic staphylokinase and alteplase for intravenous thrombolysis in ischemic stroke: analysis of hospital registry data]. Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(7):139-144. doi: 10.17116/jnevro2024124071139. Russian.
• Gusev EI, Martynov MY, Shamalov NA, Yarovaya EB, Semenov MP, Semenov AM, Orlovsky AA, Kutsenko VA, Nikonov AA, Aksentiev SB, Yunevich DS, Alasheev AM, Androfagina OV, Bobkov VV, Choroshavina KV, Gorbachev VI, Korobeynikov IV, Greshnova IV, Dobrovolskiy AV, Elemanov UA, Zhukovskaya NV, Zakharov SA, Chirkov AN, Korsunskaya LL, Nesterova VN, Nikonova AA, Nizov AA, Girivenko AI, Ponomarev EA, Popov DV, Pribylov SA, Semikhin AS, Timchenko LV, Jadan ON, Fedyanin SA, Chefranova ZY, Lykov YA, Chuprina SE, Vorobev AA, Archakov AI, Markin SS. [Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122(7):56-65. doi: 10.17116/jnevro202212207156. Russian.
• 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.
• Shamalov NA, Chefranova ZY, Yarovaya EB, Kutsenko VA, Marskaya NA, Semenov AM, Semenov MP, Ivanov SV, Romashova YA, Markin SS. Prognostic outcome of intravenous thrombolysis with non-immunogenic staphylokinase in patients aged >/= 60 years with acute ischemic stroke by THRIVE scale. J Thromb Thrombolysis. 2025 Nov 16. doi: 10.1007/s11239-025-03212-0. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): February 1, 2025

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 23, 2024
• First Posted (Actual): November 27, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; Fibrinolysis; Thrombolysis; Non-immunogenic staphylokinase
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: FORPI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No