Massive Pulmonary Embolism: Trial of Non-immunogenic Recombinant Staphylokinase VS Alteplase FORPE

NCT04688320 | Completed Phase 3 Results

• 1 other identifier: FORPE
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 23

Brief Summary

Objective: to evaluate the efficacy and safety of the Recombinant Non-immunogenic Staphylokinase with its single bolus administration in comparison with the bolus-infusion administration of the Alteplase in patients with massive pulmonary embolism

Conditions

Massive Pulmonary Embolism

Keywords

Massive pulmonary embolism; Fibrinolysis; Recombinant Non-immunogenic Staphylokinase

Outcome Measures

Primary Outcomes (1)

• Death From All Causes

  The efficacy is evaluated in terms of the number of deaths from all causes

  within 7 days

Secondary Outcomes (9)

• Systolic Pulmonary Artery Pressure Measures (V1, V2, V4, V5)

  baseline and day 1, 7, 14 after randomisation

• Haemodynamic Collapse

  within 7 days

• Recurrent Pulmonary Embolism (PE)

  within 7 days

• Death From PE

  within 30 days

• Death From All Causes

  within 30 days

Study Arms (2)

Recombinant nonimmunogenic staphylokinase

EXPERIMENTAL

lyophilisate for preparation of a solution for intravenous administration, 5 mg (745,000 IU) complete with a solvent. 15 mg (2,235,000 IU) - 3 vials, intravenously as a quick single bolus injection for 10-15 seconds, regardless of body weight.

Drug: Recombinant nonimmunogenic staphylokinase

Alteplase

EXPERIMENTAL

Alteplase® is administered in accordance with the instructions for use for pulmonary embolism( 10 mg bolus and 90 mg as IV infusion over 2 hours, maximum 100 mg). In patients weighing less than 65 kg, the total dose should not exceed 1.5 mg / kg.

Drug: Alteplase

Interventions

Recombinant nonimmunogenic staphylokinase DRUG

15 mg of drug reconstituted in 10 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds

Also known as: Fortelyzin

Recombinant nonimmunogenic staphylokinase

Alteplase DRUG

Alteplase® is administered in accordance with the instructions for use for pulmonary embolism ( 10 mg bolus and 90 mg as IV infusion over 2 hours, maximum 100 mg). In patients weighing less than 65 kg, the total dose should not exceed 1.5 mg / kg.

Also known as: Actillyze

Alteplase

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 aged 18 and over
• Verified diagnosis of massive PE (using MSCT with PA contrast)
• Signs of overload / dysfunction of the right ventricle (at least one) in combination with persistent arterial hypotension or shock
• Patient consent to use reliable contraceptive methods throughout the study and for 3 weeks after:
• women who have a negative pregnancy test and use the following contraceptives: intrauterine devices, oral contraceptives, contraceptive patch, prolonged injectable contraceptives, double barrier method of contraception. Women who are not fertile can also take part in the study (documented conditions: hysterectomy, tubal ligation, infertility, menopause for more than 1 year);
• men using barrier contraception. The study may also involve men who are not fertile (documented conditions: vasectomy, infertility)
• Availability of signed and dated informed consent of the patient to participate in the study.

You may not qualify if:

• Increased risk of bleeding:
• Extensive bleeding at present or within the previous 6 months, hemorrhagic diathesis;
• Intracranial (including subarachnoid) hemorrhage at present or in history, suspected hemorrhagic stroke;
• A history of hemorrhagic stroke or stroke of unknown etiology;
• Ischemic stroke or transient ischemic attack within the last 6 months, except for the current acute ischemic stroke within 4.5 hours;
• A history of diseases of the central nervous system (including neoplasms, aneurysms, surgery on the brain or spinal cord);
• Major surgery or major trauma within the previous 3 months, recent traumatic brain injury;
• Long-term or traumatic cardiopulmonary resuscitation (\> 2 min), delivery within the previous 10 days, recent puncture of an uncompressible blood vessel (eg, subclavian or jugular vein);
• Severe liver disease, including liver failure, cirrhosis, portal hypertension (including esophageal varices) and active hepatitis;
• Confirmed gastric or duodenal ulcer within the last three months;
• Neoplasm with an increased risk of bleeding;
• Concurrent administration of oral anticoagulants, for example, warfarin with an INR\> 1.3;
• Arterial aneurysms, developmental defects of arteries / veins;
• Severe uncontrolled arterial hypertension;
• Acute pancreatitis;

Sponsors & Collaborators

• Supergene, LLC: lead

Study Sites (23)

V.F. Dolgopolov Vyselki Central District Hospital

Vyselki, Krasnodarskiy Kray, 353100, Russia

Location

Sergiyev Posad Regional Clinical Hospital

Sergiyev Posad, Moscow Oblast, 141301, Russia

Location

Belgorod Regional Clinical Hospital of St. Joseph

Belgorod, 308007, Russia

Location

Kuzbass Cardiology center

Kemerovo, 650002, Russia

Location

Krasnoyarsk Regional Clinical Hospital

Krasnoyarsk, 660022, Russia

Location

Kursk Regional Clinical Hospital

Kursk, 305007, Russia

Location

D.D. Pletnev City Clinical Hospital

Moscow, 105077, Russia

Location

I.V. Davydovskii City Clinical Hospital

Moscow, 109240, Russia

Location

S.S. Yudin City Clinical Hospital

Moscow, 115446, Russia

Location

V.V. Vinogradov City Clinical Hospital

Moscow, 117292, Russia

Location

V.V. Veresaev City Clinical Hospital

Moscow, 127644, Russia

Location

N.V. Sklifosovsky Research Institute for Emergency Medicine

Moscow, 129090, Russia

Location

S.P. Botkin City Clinical Hospital

Moscow, Russia

Location

Murmansk Regional Clinical Hospital

Murmansk, 183047, Russia

Location

N.N. Burdenko Penza Regional Clinical hospital

Penza, 440026, Russia

Location

G.A. Zakharyin Clinical hospital №6

Penza, 440071, Russia

Location

Saint Petersburg "Mariinskaya" City Hospital

Saint Petersburg, 191014, Russia

Location

Holy Martyr Elizabeth Saint Petersburg City Hospital

Saint Petersburg, 195257, Russia

Location

V.P. Polyakov Samara Regional Clinical Cardiology Dispensary

Samara, 443070, Russia

Location

Saratov Regional Clinical Cardiology Dispensary

Saratov, 410039, Russia

Location

Tver Regional Clinical Hospital

Tver', 170036, Russia

Location

City Clinical hospital №4

Vladimir, 600009, Russia

Location

City Clinical Hospital of Emergency №25

Volgograd, 400138, Russia

Location

Related Publications (1)

• Leontyev SG, Yarovaya EB, Kutsenko VA, Ivlev OE, Soplenkova AG, Semenov AM, Semenov MP, Ivanov SV, Romashova YA, Markin SS. The Safety of Non-immunogenic Recombinant Staphylokinase in Elderly Patients With Massive Pulmonary Embolism: A Randomized Clinical Trial FORPE. Health Sci Rep. 2025 May 19;8(5):e70826. doi: 10.1002/hsr2.70826. eCollection 2025 May.

  PMID: 40391253 DERIVED

MeSH Terms

Interventions

Tissue Plasminogen Activator

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. Sergey Markin
• Organization: LLC "SuperGene"

info@supergene.ru

(495) 287-98-07

Study Officials

• Alexander I Kirienko, 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 (Actilize) by using "envelope method" of randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: At clinical centers, patients will be equally randomly distributed by the "envelope method" into two groups to receive Fortelizin® or Alteplase®. The drugs will be administered after the signed informed consent. Fortelizin® will be administered intravenously at a dose of 15 mg as a single bolus for 10-15 seconds. Alteplase® will be administered in accordance with the instructions for use. All patients will be examination for 30 days.

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 29, 2020
• Study Start: December 15, 2020
• Primary Completion: July 27, 2023
• Study Completion: July 27, 2023
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-03

Locations

RU (23)