Single Bolus Recombinant Nonimmunogenic Staphylokinase (Fortelyzin) and Bolus Infusion Alteplase in Patients With AIS

NCT03151993 | Completed Phase 3 Results

• 1 other identifier: FRIDA Stroke Trial
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 18

Brief Summary

The aim of the study is to determine if single-bolus recombinant nonimmunogenic staphylokinase is effective and save thrombolytic agent in patients with ischemic stroke in comparison to alteplase.

Conditions

Ischemic Stroke

Keywords

Acute Ischemic Stroke; Fibrinolysis; Fortelyzin

Outcome Measures

Primary Outcomes (1)

• Good Functional Recovery

  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.

  within 90 days after fibrinolysis

Secondary Outcomes (6)

• The Number of Patients With Modified Rankin Scale (0-1) + NIHSS (0-1) + Barthel (95-100)

  within 90 days after fibrinolysis

• The Median of NIHSS After 24 Hours

  after 24 hours

• The Median of NIHSS After 90 Days

  within 90 days after fibrinolysis

• All Cause Death

  within 90 days after fibrinolysis

• Intracranial Haemorrhage

  within 90 days after fibrinolysis

Study Arms (2)

Recombinant staphylokinase

EXPERIMENTAL

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

Drug: Recombinant staphylokinase

Actilyse

ACTIVE COMPARATOR

Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)

Drug: Alteplase

Interventions

Recombinant staphylokinase DRUG

10 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds

Also known as: Fortelyzin

Recombinant staphylokinase

Alteplase DRUG

Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)

Also known as: Actilyse

Actilyse

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of 18 and 80 (Version 1.0)
• Men and women aged 18 years and older, after 80 years with caution (Version 2.0)
• Verified diagnosis of ischemic stroke (from 5 to 25 points on the NIHSS scale). (Version 1.0)
• Verified diagnosis of ischemic stroke (Version 2.0)
• The time from the onset of the disease is no more than 4.5 hours.
• Informed consent received

You may not qualify if:

• The time of the onset of the first symptoms is more than 4.5 hours from the onset of the disease or the time of the onset of the first symptoms of a stroke is not known (for example, the development of a stroke during sleep - the so-called "night stroke").
• Increased sensitivity to alteplase, gentamicin (residual traces from the production process).
• Systolic blood pressure above 185 mm Hg. Art. Or diastolic blood pressure above 110 mm Hg. Art. Or the need for / in the administration of drugs to reduce blood pressure to these boundaries.
• 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.(Version 1.0)
• Light neurological symptoms (NIH \<4 points). (Version 1.0)
• Significant regression of neurological symptoms during the observation of the patient before thrombolisis (Version 2.0)
• Hemorrhagic stroke or stroke, unspecified in history.
• Strokes of any genesis in the history of a patient with diabetes mellitus.

Sponsors & Collaborators

• Supergene, LLC: lead

Study Sites (18)

Regional Clinical Hospital

Barnaul, 656024, Russia

Location

St.Iosaf's Belgorod Regional Clinical Hospital

Belgorod, 308007, Russia

Location

Regional Clinical Hospital №3

Chelyabinsk, 454021, Russia

Location

Regional Clinical Hospital

Irkutsk, 664079, Russia

Location

Regional Clinical Hospital

Kaluga, 248007, Russia

Location

Ochapowski Regional Hospital №1

Krasnodar, 350086, Russia

Location

Regional Clinical Hospital

Kursk, 305007, Russia

Location

Regional Clinical Hospital

Nizhny Novgorod, 603126, Russia

Location

Regional Clinical Hospital

Orenburg, 460018, Russia

Location

City Clinical Hospital №11

Ryazan, 390000, Russia

Location

Regional Clinical Hospital

Ryazan, 390039, Russia

Location

Regional Clinical Hospital

Saint Petersburg, 194291, Russia

Location

Regional Clinical Hospital

Samara, 443095, Russia

Location

Regional Clinical Hospital

Tver', 170036, Russia

Location

Regional Clinical Hospital

Ulyanovsk, 432017, Russia

Location

City Clinical Hospital of Emergency №25

Volgograd, 400138, Russia

Location

Regional Clinical Hospital №1

Voronezh, 394066, Russia

Location

Regional Clinical Hospital №1

Yekaterinburg, 620014, Russia

Location

Related Publications (13)

• Armstrong PW, Gershlick A, Goldstein P, Wilcox R, Danays T, Bluhmki E, Van de Werf F; STREAM Steering Committee. The Strategic Reperfusion Early After Myocardial Infarction (STREAM) study. Am Heart J. 2010 Jul;160(1):30-35.e1. doi: 10.1016/j.ahj.2010.04.007.

  PMID: 20598969 BACKGROUND

• Van de Werf F, Cannon CP, Luyten A, Houbracken K, McCabe CH, Berioli S, Bluhmki E, Sarelin H, Wang-Clow F, Fox NL, Braunwald E. Safety assessment of single-bolus administration of TNK tissue-plasminogen activator in acute myocardial infarction: the ASSENT-1 trial. The ASSENT-1 Investigators. Am Heart J. 1999 May;137(5):786-91. doi: 10.1016/s0002-8703(99)70400-x.

  PMID: 10220625 BACKGROUND

• Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators; Van De Werf F, Adgey J, Ardissino D, Armstrong PW, Aylward P, Barbash G, Betriu A, Binbrek AS, Califf R, Diaz R, Fanebust R, Fox K, Granger C, Heikkila J, Husted S, Jansky P, Langer A, Lupi E, Maseri A, Meyer J, Mlczoch J, Mocceti D, Myburgh D, Oto A, Paolasso E, Pehrsson K, Seabra-Gomes R, Soares-Piegas L, Sugrue D, Tendera M, Topol E, Toutouzas P, Vahanian A, Verheugt F, Wallentin L, White H. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999 Aug 28;354(9180):716-22. doi: 10.1016/s0140-6736(99)07403-6.

  PMID: 10475182 BACKGROUND

• Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001 Aug 25;358(9282):605-13. doi: 10.1016/S0140-6736(01)05775-0.

  PMID: 11530146 BACKGROUND

• Wallentin L, Goldstein P, Armstrong PW, Granger CB, Adgey AA, Arntz HR, Bogaerts K, Danays T, Lindahl B, Makijarvi M, Verheugt F, Van de Werf F. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation. 2003 Jul 15;108(2):135-42. doi: 10.1161/01.CIR.0000081659.72985.A8. Epub 2003 Jul 7.

  PMID: 12847070 BACKGROUND

• Vanderschueren S, Dens J, Kerdsinchai P, Desmet W, Vrolix M, De Man F, Van den Heuvel P, Hermans L, Collen D, Van de Werf F. Randomized coronary patency trial of double-bolus recombinant staphylokinase versus front-loaded alteplase in acute myocardial infarction. Am Heart J. 1997 Aug;134(2 Pt 1):213-9. doi: 10.1016/s0002-8703(97)70127-3.

  PMID: 9313600 BACKGROUND

• Collaborative Research Group of Reperfusion Therapy in Acute Myocardial Infarction. [A randomized multicenter trial comparing recombinant staphylokinase with recombinant tissue-type plasminogen activator in patients with acute myocardial infarction]. Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Aug;35(8):691-6. Chinese.

  PMID: 17963623 BACKGROUND

• Collen D. Staphylokinase: a potent, uniquely fibrin-selective thrombolytic agent. Nat Med. 1998 Mar;4(3):279-84. doi: 10.1038/nm0398-279. No abstract available.

  PMID: 9500599 BACKGROUND

• Wahlgren N, Ahmed N, Eriksson N, Aichner F, Bluhmki E, Davalos A, Erila T, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kohrmann M, Larrue V, Lees KR, Machnig T, Roine RO, Toni D, Vanhooren G; Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy Investigators. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST). Stroke. 2008 Dec;39(12):3316-22. doi: 10.1161/STROKEAHA.107.510768. Epub 2008 Oct 16.

  PMID: 18927461 BACKGROUND

• Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 Oct 17;352(9136):1245-51. doi: 10.1016/s0140-6736(98)08020-9.

  PMID: 9788453 BACKGROUND

• Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA. 1999 Dec 1;282(21):2019-26. doi: 10.1001/jama.282.21.2019.

  PMID: 10591384 BACKGROUND

• Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.

  PMID: 18815396 BACKGROUND

• 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.

  PMID: 34418399 DERIVED

Related Links

• Efficacy Guidelines. The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials.

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Eugene I. Gusev, President of the Federal Center for Brain and Neurotechnology
• Organization: Federal Center for Brain and Neurotechnology

egusev2339@gmail.com

495-280-01-74

Study Officials

• Evgenii I Gusev, MD, PhD

  Pirogov Russian National Research Medical University

  PRINCIPAL INVESTIGATOR

• Sergey S Markin, MD, PhD

  Supergene, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: All eligible patients will be randomized in two equal groups for administration recombinant nonimmunogenic staphylokinase (Fortelyzin) or alteplase (Actilyse) by using "envelope method" of randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All eligible patients will be randomized in two equal groups for administration recombinant nonimmunogenic staphylokinase (Fortelyzin) or alteplase (Actilyse) by using "envelope method" of randomization. It is an open-lable study. Each of agents will be administered no longer then 4,5 hours from symptoms onset. Comparative agent will be administered as prescribed in its instructions. All patients will be examination for 90 days

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 12, 2017
• Study Start: March 18, 2017
• Primary Completion: March 23, 2019
• Study Completion: June 20, 2019
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (18)