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

NCT ID: NCT06362746

Last Updated: 2025-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

486 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-23

Study Completion Date

2028-12-01

Brief Summary

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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)

Detailed Description

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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.

Conditions

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Pulmonary Embolism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Neither patient nor investigator knows treatment assignment. All eligible patients will be randomized in two equal groups for administration of non-immunogenic recombinant staphylokinase or placebo.

Study Groups

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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.

Group Type EXPERIMENTAL

Non-immunogenic recombinant staphylokinase

Intervention Type DRUG

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

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Fortelyzin®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Supergene, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sergey N. Tereschenko, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Locations

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RZD Medicine hospital

Barnaul, Altayskiy Kray, Russia

Site Status RECRUITING

V.F. Dolgopolov Vyselki Central District Hospital

Vyselki, Krasnodarskiy Kray, Russia

Site Status RECRUITING

Asinovskaya District Hospital

Asino, Tomsk Oblast, Russia

Site Status COMPLETED

Belgorod Regional Clinical Hospital of St. Joseph

Belgorod, , Russia

Site Status RECRUITING

Kuzbass Cardiology center

Kemerovo, , Russia

Site Status RECRUITING

Center of Neurology and Cardiology

Kirov, , Russia

Site Status RECRUITING

Regional Clinical Hospital №2

Krasnodar, , Russia

Site Status RECRUITING

Lipetsk City Hospital No. 4 "Lipetsk-Med"

Lipetsk, , Russia

Site Status RECRUITING

F.I. Inozemtsev City Clinical Hospital

Moscow, , Russia

Site Status RECRUITING

Moscow Multidisciplinary Clinical Center "Kommunarka"

Moscow, , Russia

Site Status RECRUITING

S.S. Yudin City Clinical Hospital

Moscow, , Russia

Site Status RECRUITING

V.M. Buyanov City Clinical Hospital

Moscow, , Russia

Site Status RECRUITING

S.P. Botkin City Clinical Hospital

Moscow, , Russia

Site Status RECRUITING

N.A. Semashko Nizhny Novgorod Regional Clinical Hospital

Nizhny Novgorod, , Russia

Site Status RECRUITING

N.N. Burdenko Penza Regional Clinical hospital

Penza, , Russia

Site Status WITHDRAWN

G.A. Zakharyin Clinical hospital №6

Penza, , Russia

Site Status RECRUITING

City Clinical Hospital №4

Perm, , Russia

Site Status WITHDRAWN

City Hospital No. 26

Saint Petersburg, , Russia

Site Status RECRUITING

City Hospital No. 15

Saint Petersburg, , Russia

Site Status RECRUITING

V.P. Polyakov Samara Regional Clinical Cardiology Dispensary

Samara, , Russia

Site Status RECRUITING

Tomsk regional cilinical hospital

Tomsk, , Russia

Site Status RECRUITING

Tver Regional Clinical Hospital

Tver', , Russia

Site Status RECRUITING

Ufa Emergency City Hospital

Ufa, , Russia

Site Status RECRUITING

City Clinical Hospital of Emergency medicine №25

Volgograd, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Sergey S. Markin, MD, PhD

Role: CONTACT

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

Sergey N. Tereschenko, MD, PhD

Role: CONTACT

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

Facility Contacts

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Mikhail I. Neimark, MD, PhD

Role: primary

(3852) 757-966 ext. +7

Valerii V. Makukhin, PhD

Role: primary

(86199) 123-53 ext. +7

Sergei L Konstantinov, MD

Role: primary

Vasilii V. Kashtalap, MD, PhD

Role: primary

+7 (3842) 64-22-41

Oleg V. Solovyev, PhD

Role: primary

(8332) 56-35-74 ext. +7

Tamara A. Chirva, MD

Role: primary

(861) 222-000-2 ext. +7

Roman S. Ovchinnikov, PhD

Role: primary

(474) 225-81-00 ext. +7

Alexander V. Lubavin, PhD

Role: backup

Evgenia V. Tavlueva, PhD

Role: primary

(495) 366-77-19 ext. +7

Anastasia Yu Lebedeva, PhD

Role: primary

(495) 744-07-03 ext. +7

Bogdan B Orlov, MD, PhD

Role: primary

7 (499) 612-45-66

Yury V. Gavrilov, PhD

Role: primary

(495) 321-54-92 ext. +7

Yuri V. Karabach, PhD

Role: primary

(499) 490-03-03 ext. +7

Galina V. Kovakeva, PhD

Role: primary

(831) 436-40-01 ext. +7

Elena S. Panina, PhD

Role: primary

(8412) 98-33-55 ext. +7

Dmitry A. Svirido, PhD

Role: primary

(812) 415-18-88 ext. +7

Boris M. Goloschekin, PhD

Role: primary

(812) 338-96-98 ext. +7

Dmitrii V Duplyakov, MD, PhD

Role: primary

8 (846) 373-70-63

Sergei I. Antipov, PhD

Role: primary

(382) 263-00-63 ext. +7

Vladimir V. Bobkov, PhD

Role: primary

(4822)36-40-93 ext. +7

Marat S. Kashaev, PhD

Role: primary

(347) 291-29-96 ext. +7

Eduard A. Ponomarev, PhD

Role: primary

(8442) 58-16-61 ext. +7

References

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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.

Reference Type RESULT
PMID: 39454884 (View on PubMed)

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.

Reference Type RESULT
PMID: 40391253 (View on PubMed)

Other Identifiers

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FORPE-2

Identifier Type: -

Identifier Source: org_study_id

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