Non-immunogenic Recombinant Staphylokinase vs Placebo in Patients With Intermediate High-risk Pulmonary Embolism

November 27, 2025 updated by: Supergene, LLC

Multicenter, Double-blind, Randomized, Placebo-controlled Trial of the Efficacy and Safety of a Single Bolus Administration of Non-immunogenic Recombinant Staphylokinase in Patients With Intermediate High-risk Pulmonary Embolism (FORPE-2)

Objective: to evaluate the efficacy and safety of the non-immunogenic recombinant staphylokinase with its single bolus administration in comparison with placebo in normotensive patients with intermediate high-risk pulmonary embolism (PE)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

For patients with massive PE thrombolysis can be life-saving and may reduce a pulmonary obstruction, pulmonary hypertension, and right ventricle dysfunction. Efficacy of the thrombolytic therapy has been proven in patients with high-risk pulmonary embolism accompanied by shock or systemic hypotension. However, the question of whether thrombolytic therapy can improve the clinical outcome of hemodynamically stable patients, i.e. with PE of intermediate high-risk, still remains controversial.

In PEITHO trial tenecteplase, administered as a single bolus at a dose of 30-50 mg depending on body weight was compared with a placebo in patients with intermediate high-risk PE with right ventricular dysfunction. Efficacy of tenecteplase was combined with a significant (6.3%) risk of hemorrhagic stroke, which did not allow tenecteplase to be included in the list of recommended thrombolytics for PE treatment.

PEITHO-3 trial has now begun, in which patients with intermediate high-risk PE are given a reduced dose of alteplase (0.6 mg/kg infusion with the total dose not exceeding 50 mg) compared with placebo.

Staphylokinase is a thrombolytic agent with high biological activity. Amino acid substitutions - including Lys74Ala, Glu75Ala, and Arg77Ala - resulted in a more than 200-times reduction in titres of neutralising antistaphylokinase IgGs in patients with ST-elevation myocardial infarction. In FORPE trial non-immunogenic recombinant staphylokinase was non-inferior as compared with alteplase in patients with high-risk massive PE.

The main objectives of this study: to assess the efficacy, safety and possible adverse events of the non-immunogenic recombinant staphylokinase with its single bolus administration in normotensive patients with intermediate high-risk PE in comparison with placebo.

Study Type

Interventional

Enrollment (Estimated)

486

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Russia
      • Belgorod, Russia, 308007
        • Recruiting
        • Belgorod Regional Clinical Hospital of St. Joseph
        • Contact:
        • Principal Investigator:
          • Sergei L Konstantinov, MD
      • Kemerovo, Russia, 650002
        • Recruiting
        • Kuzbass Cardiology center
        • Contact:
          • Vasilii V. Kashtalap, MD, PhD
          • Phone Number: +7 (3842) 64-22-41
          • Email: v_kash@mail.ru
        • Principal Investigator:
          • Vasilii V. Kashtalap, MD, PhD
      • Kirov, Russia, 610035
        • Recruiting
        • Center of Neurology and Cardiology
        • Contact:
          • Oleg V. Solovyev, PhD
          • Phone Number: +7 (8332) 56-35-74
          • Email: ckn@medkirov.ru
        • Principal Investigator:
          • Oleg V. Solovyev, PhD
      • Krasnodar, Russia, 350012
        • Recruiting
        • Regional Clinical Hospital №2
        • Contact:
        • Principal Investigator:
          • Tamara A. Chirva, MD
      • Lipetsk, Russia, 398006
        • Recruiting
        • Lipetsk City Hospital No. 4 "Lipetsk-Med"
        • Contact:
          • Roman S. Ovchinnikov, PhD
          • Phone Number: +7 (474) 225-81-00
          • Email: romzec@yandex.ru
        • Contact:
          • Alexander V. Lubavin, PhD
        • Principal Investigator:
          • Roman S. Ovchinnikov, PhD
      • Moscow, Russia, 105187
        • Recruiting
        • F.I. Inozemtsev City Clinical Hospital
        • Contact:
          • Evgenia V. Tavlueva, PhD
          • Phone Number: +7 (495) 366-77-19
          • Email: tavlev1@mail.ru
        • Principal Investigator:
          • Evgenia V. Tavlueva, PhD
      • Moscow, Russia, 108814
        • Recruiting
        • Moscow Multidisciplinary Clinical Center "Kommunarka"
        • Principal Investigator:
          • Anastasia Yu Lebedeva, PhD
        • Contact:
      • Moscow, Russia, 115446
        • Recruiting
        • S.S. Yudin City Clinical Hospital
        • Contact:
          • Bogdan B Orlov, MD, PhD
          • Phone Number: 7 (499) 612-45-66
          • Email: bborlov@mail.ru
        • Principal Investigator:
          • Bogdan B Orlov, MD, PhD
      • Moscow, Russia
        • Recruiting
        • S.P. Botkin City Clinical Hospital
        • Contact:
        • Principal Investigator:
          • Yuri V. Karabach, PhD
      • Moscow, Russia, 115516
        • Recruiting
        • V.M. Buyanov City Clinical Hospital
        • Contact:
        • Principal Investigator:
          • Yury V. Gavrilov, Gavrilov
      • Nizhny Novgorod, Russia, 603093
        • Recruiting
        • N.A. Semashko Nizhny Novgorod Regional Clinical Hospital
        • Contact:
          • Galina V. Kovakeva, PhD
          • Phone Number: +7 (831) 436-40-01
          • Email: kogaval@mail.ru
        • Principal Investigator:
          • Galina V. Kovakeva, PhD
      • Penza, Russia, 440071
        • Recruiting
        • G.A. Zakharyin Clinical hospital №6
        • Contact:
        • Principal Investigator:
          • Elena S. panina, PhD
      • Penza, Russia, 440026
        • Withdrawn
        • N.N. Burdenko Penza Regional Clinical hospital
      • Perm, Russia, 614107
        • Withdrawn
        • City Clinical Hospital №4
      • Saint Petersburg, Russia, 196247
        • Recruiting
        • City Hospital No. 26
        • Contact:
        • Principal Investigator:
          • Dmitry A. Svirido, PhD
      • Saint Petersburg, Russia, 198205
        • Recruiting
        • City Hospital No. 15
        • Contact:
        • Principal Investigator:
          • Boris M. Goloschekin, PhD
      • Samara, Russia, 443070
        • Recruiting
        • V.P. Polyakov Samara Regional Clinical Cardiology Dispensary
        • Contact:
        • Principal Investigator:
          • Dmitrii V Duplyakov, MD, PhD
      • Tomsk, Russia, 634063
        • Recruiting
        • Tomsk regional cilinical hospital
        • Contact:
        • Principal Investigator:
          • Sergei I. Antipov, PhD
      • Tver', Russia, 170036
        • Recruiting
        • Tver Regional Clinical Hospital
        • Principal Investigator:
          • Vladimir V. Bobkov, PhD
        • Contact:
      • Ufa, Russia, 450092
        • Recruiting
        • Ufa Emergency City Hospital
        • Contact:
        • Principal Investigator:
          • Marat S. Kashaev, PhD
      • Volgograd, Russia, 400138
        • Recruiting
        • City Clinical Hospital of Emergency medicine №25
        • Contact:
        • Principal Investigator:
          • Eduard A. Ponomarev, PhD
    • Altayskiy Kray
      • Barnaul, Altayskiy Kray, Russia, 656038
        • Recruiting
        • RZD Medicine hospital
        • Contact:
          • Mikhail I. Neimark, MD, PhD
          • Phone Number: +7 (3852) 757-966
          • Email: mineimark@asmu.ru
        • Principal Investigator:
          • Mikhail I. Neimark, MD, PhD
    • Krasnodarskiy Kray
      • Vyselki, Krasnodarskiy Kray, Russia, 353100
        • Recruiting
        • V.F. Dolgopolov Vyselki Central District Hospital
        • Contact:
          • Valerii V. Makukhin, PhD
          • Phone Number: +7 (86199) 123-53
          • Email: makuhinv@mail.ru
        • Principal Investigator:
          • Valerii V. Makukhin, PhD
    • Tomsk Oblast
      • Asino, Tomsk Oblast, Russia, 636840
        • Completed
        • Asinovskaya District Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women aged 18 and over.
  • Verified diagnosis of intermediate high-risk PE using CTPA, no more than two weeks from the symptoms onset.
  • RV dysfunction, defined as a RV/LV ventricular end-diastolic diameter ratio more than 1.0 assessed by CTPA.

  • Increased risk of early death or hemodynamic collapse, defined by one of the following criteria:

    1. systolic blood pressure less than 110 mm Hg, but not less than 90 mm Hg for more than 15 minutes;
    2. respiratory rate more than 20 per minute or SpO2 less than 90% without oxygen support;
    3. chronic heart failure with left ventricular ejection fraction less than 40%.
  • Serum troponin I level more than 14 pg/mL in patients under 75 years, and more than 45 pg/mL in patients aged 75 years or older.

  • 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.

Exclusion Criteria:

  • High-risk PE with hemodynamic instability.

  • Increased risk of bleeding:

    • extensive bleeding at present or within the previous 6 months;
    • intracranial (including subarachnoid) hemorrhage at present or in history;
    • hemorrhagic stroke within the last 6 months;
    • a history of diseases of the central nervous system (including neoplasms, aneurysms);
    • intracranial or spinal surgical interventions within the last 2 months;
    • major surgery or major trauma within the previous 4 weeks;
    • recent puncture of an incompressible 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 3 months;
    • neoplasm with an increased risk of bleeding;
    • simultaneous administration of Dabigatran without prior administration of idarucizumab;
    • arterial aneurysms, developmental defects of arteries / veins;
    • acute pancreatitis;
    • bacterial endocarditis, pericarditis;
    • suspicion of aortic dissecting aneurysm;
    • any other conditions, in the opinion of the investigator, associated with a high risk of bleeding.
  • Lactation, pregnancy.
  • Known hypersensitivity to the non-immunogenic recombinant staphylokinase.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Non-immunogenic recombinant staphylokinase
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: Non-immunogenic recombinant staphylokinase
15 mg of drug reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds
Other Names:
  • Fortelyzin®
Placebo Comparator: Placebo
15 mg of placebo reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds
Drug: Placebo
15 mg of placebo reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of death from any cause or hemodynamic collapse or recurrent PE
Time Frame: within 30 days
The efficacy is evaluated in terms of the number of death from any cause or hemodynamic collapse or recurrent PE
within 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Right/left ventricular (RV/LV) end-diastolic diameter ratio
Time Frame: within 24 hours
The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to echocardiography
within 24 hours
RV/LV end-diastolic diameter ratio
Time Frame: within 24 hours
The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to computed tomography pulmonary angiography (CTPA)
within 24 hours
RV/LV end-diastolic diameter ratio
Time Frame: within 30 days
The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to echocardiography
within 30 days
Right ventricular (RV) end-diastolic volume
Time Frame: within 24 hours
The efficacy is evaluated in terms of the RV end-diastolic volume according to CTPA
within 24 hours
Qanadli index
Time Frame: within 24 hours
The efficacy is evaluated in terms of Qanadli index according to CTPA in points from 0 to 40, where 0 points - absence of thrombotic masses in the pulmonary artery, 40 points - complete occlusion of the pulmonary artery
within 24 hours
Systolic pulmonary artery pressure
Time Frame: within 24 hours
The efficacy is evaluated in terms of the systolic pulmonary artery pressure according to echocardiography
within 24 hours
In hospital death from all causes (assessed up to day 7)
Time Frame: In hospital period (assessed up to day 7)
The efficacy is evaluated in terms of the in hospital death from all causes (assessed up to day 7)
In hospital period (assessed up to day 7)
Death from all causes
Time Frame: within 30 days
The efficacy is evaluated in terms of the death from all causes
within 30 days
Safety endpoint - hemorrhagic stroke
Time Frame: within 30 days
The efficacy is evaluated in terms of the hemorrhagic stroke
within 30 days
Safety endpoint - BARC type 3 and 5 bleeding
Time Frame: within 30 days
The efficacy is evaluated in terms of the Bleeding Academic Research Consortium definitions, where type 3a is an overt bleeding with hemoglobin drop of 3 to 5 g/dL and any transfusion with overt bleeding; type 3b is a bleeding requiring surgical intervention or intravenous vasoactive agents; type 3c is an intracranial hemorrhage; type 5 is fatal bleeding.
within 30 days
Safety endpoint - number and severity of adverse events (AEs) and serious AEs in organs and systems
Time Frame: within 30 days
The efficacy is evaluated in terms of the number and severity of AEs and serious AEs in organs and systems
within 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Supergene, LLC

Investigators

  • Principal Investigator: Sergey N. Tereschenko, MD, PhD, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 23, 2024

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

April 2, 2024

First Submitted That Met QC Criteria

April 8, 2024

First Posted (Actual)

April 12, 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

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FORPE-2

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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