Clinical trial NCT06707987: Post-registration Trial of the Non-immunogenic Staphylokinase in Acute Ischemic Stroke (FORPI Registry)
Official title: 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)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Ischemic Stroke
Keywords: Acute ischemic stroke
Fibrinolysis
Thrombolysis
Non-immunogenic staphylokinase
Lead sponsor: Supergene, LLC
Sponsor class: INDUSTRY
Collaborators: name: Federal Center of Cerebrovascular Pathology and Stroke, Russian Federation Ministry of Health
First posted: 2024-11-27
Enrollment: 23250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Modified Rankin Scale (mRS) score of 0-2 on day 90 after drug administration
timeFrame: day 90 after drug administration
Secondary outcomes:
measure: mRS score on day 90 after drug administration
timeFrame: day 90 after drug administration
measure: The National Institutes of Health Stroke Scale (NIHSS) at 24 hours after drug administration
timeFrame: 24 hours after drug administration
measure: NIHSS on day 7 after drug administration
timeFrame: day 7 after drug administration
Other outcomes:
measure: All-cause mortality
timeFrame: day 90 after drug administration
measure: Intracranial haemorrhage
timeFrame: day 90 after drug administration
measure: Symptomatic intracerebral haemorrhage
timeFrame: day 90 after drug administration
measure: Major bleedings
timeFrame: day 90 after drug administration
measure: Thrombectomy
timeFrame: day 90 after drug administration
measure: Allergic reactions
timeFrame: day 90 after drug administration
measure: Pulmonary embolism
timeFrame: day 90 after drug administration
Locations:
city: Moscow
country: Russian Federation
facility: Federal Brain and Neurotechnology Center
Study officials:
affiliation: Federal Brain and Neurotechnology Center
name: Nikolay A. Shamalov, MD, PhD Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.