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Pulmonary EmbolismPhase 3NCT06362746

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

A Phase 3 study testing Non-immunogenic recombinant staphylokinase in people with Pulmonary Embolism, run by Supergene, LLC at 24 sites in Russia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Embolism
What is being tested?
Non-immunogenic recombinant staphylokinase
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
486 participants
Where
24 sitesRussia
Study dates
23 May 2024to 1 Dec 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • systolic blood pressure less than 110 mm Hg, but not less than 90 mm Hg for more than 15 minutes;
  • respiratory rate more than 20 per minute or SpO2 less than 90% without oxygen support;
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  • 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.

Who cannot join

  • 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);
Show all 20Show fewer
  • 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.

Trial locations and contacts

24 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Sergey S. Markin, MD, PhD contact

(906) 796-89-06 ext. +7

ssmarkin2153@mail.ru

Sergey N. Tereschenko, MD, PhD contact

(495) 150-44-19 ext. +7

stereschenko@yandex.ru

24 sites in 1 country

Russia24 sites, 21 recruiting

  • Asinovskaya District Hospital

    Asino, Tomsk Oblast, 636840

    Completed

  • RZD Medicine hospital

    Barnaul, Altayskiy Kray, 656038

    Mikhail I. Neimark, MD, PhD, (3852) 757-966 ext. +7, mineimark@asmu.ru

    Mikhail I. Neimark, MD, PhD

    Recruiting

  • Belgorod Regional Clinical Hospital of St. Joseph

    Belgorod, 308007

    Sergei L Konstantinov, MD, konstantinov5@yandex.ru

    Sergei L Konstantinov, MD

    Recruiting

  • Kuzbass Cardiology center

    Kemerovo, 650002

    Vasilii V. Kashtalap, MD, PhD, +7 (3842) 64-22-41, v_kash@mail.ru

    Vasilii V. Kashtalap, MD, PhD

    Recruiting

  • Center of Neurology and Cardiology

    Kirov, 610035

    Oleg V. Solovyev, PhD, (8332) 56-35-74 ext. +7, ckn@medkirov.ru

    Oleg V. Solovyev, PhD

    Recruiting

  • Regional Clinical Hospital №2

    Krasnodar, 350012

    Tamara A. Chirva, MD, (861) 222-000-2 ext. +7, makuhinv@mail.ru

    Tamara A. Chirva, MD

    Recruiting

  • Lipetsk City Hospital No. 4 "Lipetsk-Med"

    Lipetsk, 398006

    Roman S. Ovchinnikov, PhD, (474) 225-81-00 ext. +7, romzec@yandex.ru

    Alexander V. Lubavin, PhD

    Recruiting

  • F.I. Inozemtsev City Clinical Hospital

    Moscow, 105187

    Evgenia V. Tavlueva, PhD, (495) 366-77-19 ext. +7, tavlev1@mail.ru

    Evgenia V. Tavlueva, PhD

    Recruiting

  • Moscow Multidisciplinary Clinical Center "Kommunarka"

    Moscow, 108814

    Anastasia Yu Lebedeva, PhD, (495) 744-07-03 ext. +7, alebedeva-md@yandex.ru

    Anastasia Yu Lebedeva, PhD

    Recruiting

  • S.S. Yudin City Clinical Hospital

    Moscow, 115446

    Bogdan B Orlov, MD, PhD, 7 (499) 612-45-66, bborlov@mail.ru

    Bogdan B Orlov, MD, PhD

    Recruiting

  • V.M. Buyanov City Clinical Hospital

    Moscow, 115516

    Yury V. Gavrilov, PhD, (495) 321-54-92 ext. +7, gavrilovyv@zdrav.mos.ru

    Yury V. Gavrilov, Gavrilov

    Recruiting

  • S.P. Botkin City Clinical Hospital

    Moscow

    Yuri V. Karabach, PhD, (499) 490-03-03 ext. +7, yu.karabach@ya.ru

    Yuri V. Karabach, PhD

    Recruiting

  • N.A. Semashko Nizhny Novgorod Regional Clinical Hospital

    Nizhny Novgorod, 603093

    Galina V. Kovakeva, PhD, (831) 436-40-01 ext. +7, kogaval@mail.ru

    Galina V. Kovakeva, PhD

    Recruiting

  • N.N. Burdenko Penza Regional Clinical hospital

    Penza, 440026

    Withdrawn

  • G.A. Zakharyin Clinical hospital №6

    Penza, 440071

    Elena S. Panina, PhD, (8412) 98-33-55 ext. +7, panina.es@mail.ru

    Elena S. panina, PhD

    Recruiting

  • City Clinical Hospital №4

    Perm, 614107

    Withdrawn

  • City Hospital No. 26

    Saint Petersburg, 196247

    Dmitry A. Svirido, PhD, (812) 415-18-88 ext. +7, teratology@mail.ru

    Dmitry A. Svirido, PhD

    Recruiting

  • City Hospital No. 15

    Saint Petersburg, 198205

    Boris M. Goloschekin, PhD, (812) 338-96-98 ext. +7, bgoloschekin@yandex.ru

    Boris M. Goloschekin, PhD

    Recruiting

  • V.P. Polyakov Samara Regional Clinical Cardiology Dispensary

    Samara, 443070

    Dmitrii V Duplyakov, MD, PhD, 8 (846) 373-70-63, duplyakov@yahoo.com

    Dmitrii V Duplyakov, MD, PhD

    Recruiting

  • Tomsk regional cilinical hospital

    Tomsk, 634063

    Sergei I. Antipov, PhD, (382) 263-00-63 ext. +7, sergey.antipov1974@gmail.com

    Sergei I. Antipov, PhD

    Recruiting

  • Tver Regional Clinical Hospital

    Tver', 170036

    Vladimir V. Bobkov, PhD, (4822)36-40-93 ext. +7, vladibo73@gmail.com

    Vladimir V. Bobkov, PhD

    Recruiting

  • Ufa Emergency City Hospital

    Ufa, 450092

    Marat S. Kashaev, PhD, (347) 291-29-96 ext. +7, mkashaev@gmail.com

    Marat S. Kashaev, PhD

    Recruiting

  • City Clinical Hospital of Emergency medicine №25

    Volgograd, 400138

    Eduard A. Ponomarev, PhD, (8442) 58-16-61 ext. +7, ponomarev67@mail.ru

    Eduard A. Ponomarev, PhD

    Recruiting

  • V.F. Dolgopolov Vyselki Central District Hospital

    Vyselki, Krasnodarskiy Kray, 353100

    Valerii V. Makukhin, PhD, (86199) 123-53 ext. +7, makuhinv@mail.ru

    Valerii V. Makukhin, PhD

    Recruiting

Other trials in Russia

About this study

Official title: 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)

Read the 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.

Being tested
Non-immunogenic recombinant staphylokinase, Placebo
Keywords
Intermediate high-risk pulmonary embolism, Fibrinolysis, Recombinant Non-immunogenic Staphylokinase
Medical subject headings
Pulmonary Embolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Non-immunogenic recombinant staphylokinaseDrug

    Also called Fortelyzin®

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

  • PlaceboDrug

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

Study groups in NCT06362746
Study groupRoleWhat they receive
Non-immunogenic recombinant staphylokinaseExperimentallyophilisate 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.
Receives: Drug: Non-immunogenic recombinant staphylokinase
PlaceboPlacebo comparator15 mg of placebo reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of death from any cause or hemodynamic collapse or recurrent PE

    The efficacy is evaluated in terms of the number of death from any cause or hemodynamic collapse or recurrent PE

    Measured: within 30 days

Secondary outcomes (11)

  1. Right/left ventricular (RV/LV) end-diastolic diameter ratio

    The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to echocardiography

    Measured: within 24 hours

  2. RV/LV end-diastolic diameter ratio

    The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to computed tomography pulmonary angiography (CTPA)

    Measured: within 24 hours

  3. RV/LV end-diastolic diameter ratio

    The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to echocardiography

    Measured: within 30 days

  4. Right ventricular (RV) end-diastolic volume

    The efficacy is evaluated in terms of the RV end-diastolic volume according to CTPA

    Measured: within 24 hours

  5. Qanadli index

    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

    Measured: within 24 hours

  6. Systolic pulmonary artery pressure

    The efficacy is evaluated in terms of the systolic pulmonary artery pressure according to echocardiography

    Measured: within 24 hours

  7. In hospital death from all causes (assessed up to day 7)

    The efficacy is evaluated in terms of the in hospital death from all causes (assessed up to day 7)

    Measured: In hospital period (assessed up to day 7)

  8. Death from all causes

    The efficacy is evaluated in terms of the death from all causes

    Measured: within 30 days

  9. Safety endpoint - hemorrhagic stroke

    The efficacy is evaluated in terms of the hemorrhagic stroke

    Measured: within 30 days

  10. Safety endpoint - BARC type 3 and 5 bleeding

    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.

    Measured: within 30 days

  11. Safety endpoint - number and severity of adverse events (AEs) and serious AEs in organs and systems

    The efficacy is evaluated in terms of the number and severity of AEs and serious AEs in organs and systems

    Measured: within 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2024
  2. Study start23 May 2024
  3. Primary completion1 Jun 2028 (estimated)
  4. Study completion1 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
At clinical sites patients will be equally randomized into two groups to receive non-immunogenic recombinant staphylokinase or placebo. Non-immunogenic recombinant staphylokinase or placebo will be administered intravenously at a dose of 15 mg as a single bolus for 10-15 seconds. All patients will be examined for 30 days.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
486 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06362746
Sponsor's protocol ID
FORPE-2
Status last verified
Nov 2025
First submitted
2 Apr 2024
Last updated
5 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kirienko AI, Leontyev SG, Tereschenko SN, Yavelov IS, Shakhnovich RM, Erlikh AD, Talibov OB, Yarovaya EB, Semenov AM, Semenov MP, Ivanov SV, Beregovykh VV, Archakov AI, Markin SS; FORPE study group. Non-immunogenic recombinant staphylokinase versus alteplase for patients with massive pulmonary embolism: a randomized open-label, multicenter, parallel-group, non-inferiority trial, FORPE. J Thromb Haemost. 2025 Feb;23(2):657-667. doi: 10.1016/j.jtha.2024.09.035. Epub 2024 Oct 23.

    PubMed 39454884

  • 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.

    PubMed 40391253

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Non-immunogenic recombinant staphylokinase in people with Pulmonary Embolism, run by Supergene, LLC at 24 sites in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sergey S. Markin, MD, PhD ((906) 796-89-06 ext. +7, ssmarkin2153@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of death from any cause or hemodynamic collapse or recurrent PE (time frame: within 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06362746, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.

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