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

NCT06362746 | Recruiting Phase 3 DMC

• 1 other identifier: FORPE-2
• Study Type: interventional
• Target: 486
• Locations: 1 country
• Sites: 24

Brief 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)

Conditions

Pulmonary Embolism

Keywords

Intermediate high-risk pulmonary embolism; Fibrinolysis; Recombinant Non-immunogenic Staphylokinase

Outcome Measures

Primary Outcomes (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

  within 30 days

Secondary Outcomes (11)

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

  within 24 hours

• RV/LV end-diastolic diameter ratio

  within 24 hours

• RV/LV end-diastolic diameter ratio

  within 30 days

• Right ventricular (RV) end-diastolic volume

  within 24 hours

• Qanadli index

  within 24 hours

Study Arms (2)

Non-immunogenic recombinant 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: Non-immunogenic recombinant staphylokinase

Placebo

PLACEBO COMPARATOR

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

Interventions

Non-immunogenic recombinant staphylokinase 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

Also known as: Fortelyzin®

Non-immunogenic recombinant staphylokinase

Placebo 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

Placebo

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 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;
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Supergene, LLC: lead

Study Sites (24)

RZD Medicine hospital

Barnaul, Altayskiy Kray, 656038, Russia

RECRUITING

V.F. Dolgopolov Vyselki Central District Hospital

Vyselki, Krasnodarskiy Kray, 353100, Russia

RECRUITING

Asinovskaya District Hospital

Asino, Tomsk Oblast, 636840, Russia

COMPLETED

Belgorod Regional Clinical Hospital of St. Joseph

Belgorod, 308007, Russia

RECRUITING

Kuzbass Cardiology center

Kemerovo, 650002, Russia

RECRUITING

Center of Neurology and Cardiology

Kirov, 610035, Russia

RECRUITING

Regional Clinical Hospital №2

Krasnodar, 350012, Russia

RECRUITING

Lipetsk City Hospital No. 4 "Lipetsk-Med"

Lipetsk, 398006, Russia

RECRUITING

F.I. Inozemtsev City Clinical Hospital

Moscow, 105187, Russia

RECRUITING

Moscow Multidisciplinary Clinical Center "Kommunarka"

Moscow, 108814, Russia

RECRUITING

S.S. Yudin City Clinical Hospital

Moscow, 115446, Russia

RECRUITING

V.M. Buyanov City Clinical Hospital

Moscow, 115516, Russia

RECRUITING

S.P. Botkin City Clinical Hospital

Moscow, Russia

RECRUITING

N.A. Semashko Nizhny Novgorod Regional Clinical Hospital

Nizhny Novgorod, 603093, Russia

RECRUITING

N.N. Burdenko Penza Regional Clinical hospital

Penza, 440026, Russia

WITHDRAWN

G.A. Zakharyin Clinical hospital №6

Penza, 440071, Russia

RECRUITING

City Clinical Hospital №4

Perm, 614107, Russia

WITHDRAWN

City Hospital No. 26

Saint Petersburg, 196247, Russia

RECRUITING

City Hospital No. 15

Saint Petersburg, 198205, Russia

RECRUITING

V.P. Polyakov Samara Regional Clinical Cardiology Dispensary

Samara, 443070, Russia

RECRUITING

Tomsk regional cilinical hospital

Tomsk, 634063, Russia

RECRUITING

Tver Regional Clinical Hospital

Tver', 170036, Russia

RECRUITING

Ufa Emergency City Hospital

Ufa, 450092, Russia

RECRUITING

City Clinical Hospital of Emergency medicine №25

Volgograd, 400138, Russia

RECRUITING

Related Publications (2)

• 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.

  PMID: 39454884 RESULT

• 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 RESULT

MeSH Terms

Conditions

Pulmonary Embolism

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Sergey N. Tereschenko, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sergey S. Markin, MD, PhD

CONTACT

(906) 796-89-06; ssmarkin2153@mail.ru

Sergey N. Tereschenko, MD, PhD

CONTACT

(495) 150-44-19; stereschenko@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 12, 2024
• Study Start: May 23, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

RU (24)