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Randomized Controlled Trial
. 2025 Feb;23(2):657-667.
doi: 10.1016/j.jtha.2024.09.035. Epub 2024 Oct 23.

Non-immunogenic recombinant staphylokinase versus alteplase for patients with massive pulmonary embolism: a randomized open-label, multicenter, parallel-group, non-inferiority trial, FORPE

Alexander I Kirienko  1 , Stanislav G Leontyev  2 , Sergey N Tereschenko  3 , Igor S Yavelov  4 , Roman M Shakhnovich  5 , Alexey D Erlikh  6 , Oleg B Talibov  7 , Elena B Yarovaya  8 , Andrey M Semenov  9 , Michail P Semenov  9 , Sergey V Ivanov  10 , Valery V Beregovykh  11 , Alexander I Archakov  11 , Sergey S Markin  10 ; FORPE study group
Collaborators, Affiliations
Randomized Controlled Trial

Non-immunogenic recombinant staphylokinase versus alteplase for patients with massive pulmonary embolism: a randomized open-label, multicenter, parallel-group, non-inferiority trial, FORPE

Alexander I Kirienko et al. J Thromb Haemost. 2025 Feb.

Abstract

Background: Non-immunogenic staphylokinase is a modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and fibrin selectivity.

Objectives: To assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with those of alteplase in patients with massive pulmonary embolism and hemodynamic instability.

Methods: A randomized, open-label, multicenter, parallel-group, non-inferiority trial, the FORPE (FORtelyzin Pulmionary Embolism), was conducted in Russia. A total of 310 patients aged 18 years and older with computed tomography pulmonary angiography confirmed diagnosis of massive pulmonary embolism and right ventricular dysfunction were included. The patients were randomly assigned to receive either non-immunogenic staphylokinase (15 mg) or alteplase (100 mg), both administered intravenously. The primary efficacy endpoint was death from all causes within 7 days of randomization.

Results: A total of 155 patients were randomly assigned to receive non-immunogenic staphylokinase, and 155 received alteplase. In the non-immunogenic staphylokinase group, the primary efficacy endpoint was 2% in the intention-to-treat population, while in the alteplase group, it was 3% (odds ratio, 0.75; 95% CI, 0.11-4.49; P = 1.00). The difference in the primary efficacy endpoint was 0.6% (95% CI, -2.8% to 4.0%). Thus, the lower limit of the 95% CI did not cross the margin of non-inferiority. No cases of major bleeding were recorded in the non-immunogenic staphylokinase group, whereas there were 5 cases of major bleeding (3%; P = .09) in the alteplase group.

Conclusion: Non-immunogenic staphylokinase was non-inferior to alteplase in patients with massive pulmonary embolism. Future observational studies are needed to assess its safety and efficacy.

Keywords: massive pulmonary embolism; non-immunogenic staphylokinase; randomized clinical trial; thrombolytic therapy.

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Conflict of interest statement

Declaration of competing interests S.G.L. has received lectureship fees from Aspen, Bayer, Medak, Pfizer, Sanofi, Servier, SuperGene, and Takeda and declared a patent issued for a method for the treatment of patients with pulmonary embolism. S.N.T. participated in clinical trials by AstraZeneca, Novartis, Pfizer, Sanofi, Servier, and Takeda; has received lectureship fees from Akrikhin, AstraZeneca, Bayer, Boehringer Ingelheim, Berlin-Chemie AG, Gedeon Richter, Novartis, Pfizer, Sanofi, SuperGene, and Takeda; clinical research grants from Amgen, AstraZeneca, Novartis, Pfizer, and Servier. I.S.Y. has received lectureship fees from Abbott, Alfasigma, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, KRKA, Pfaizer, Sanofi, Servier, and Stada. R.M.S. has received lectureship fees from AstraZeneca, Berlin-Chemie AG, Novartis, Pfizer, Sanofi, and SuperGene. A.D.E. has received lectureship fees from AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novartis, Pfizer, Phillips, Sanofi-Aventis, Servier, and Zentiva. O.B.T. has received lectureship fees from Amgen, AstraZeneca, Generium, Novartis, Pfizer, and R-Pharm. M.P.S., A.M.S., S.V.I., and S.S.M. are employees of SuperGene. M.P.S., A.M.S., and S.S.M. declare a patent issued for a method for the treatment of patients with pulmonary embolism. E.A.P. participated in clinical trials by Biocad and has received lecture fees from Alfasigma, Bayer, and Servier. V.V.B. participated in clinical trials by AstraZeneca and has received lecture fees from Bayer, SuperGene, Pfizer, Boehringer Ingelheim, AstraZeneca, and Sanofi. S.L.K. participated in clinical trials by SuperGene and has received lecture fees from SuperGene. D.V.D. participated in clinical trials by Actelion Pharmaceuticals, Amgen, Bayer, Boehringer Ingelheim, and Novartis. V.V.K. participated in clinical trials by Boehringer Ingelheim, Generium, and Novartis and has received lecture fees from Bayer, Novartis, Pfizer, Stada, Sanofi, and Servier. V.E.O. participated in clinical trials by Boehringer Ingelheim, Novartis, and Servier and has received lecture fees from Akrikhin, AstraZeneca, and Sanofi. V.V.M. participated in clinical trials by Amgen and Pharmasyntez. All other authors declare no competing interests.

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