Post-registration Trial of the Non-immunogenic Staphylokinase in Massive Pulmonary Embolism

An Open, Prospective, Non-interventional, Multicentre, Controlled Study of Safety and Efficacy of the Thrombolysis With the Non-immunogenic Staphylokinase in Patients With Massive Pulmonary Embolism (FORPE Registry)

The aim of FORPE Registry is to study the safety and efficacy of the non-immunogenic staphylokinase in patients with massive pulmonary embolism in routine clinical practice.

In November 2023 a multicenter, open-label, randomized non-inferiority trial of the efficacy and safety of the non-immunogenic staphylokinase (Fortelyzin®) compared with alteplase (Actilyse®) in patients with massive pulmonary embolism (FORPE) has been completed (NCT04688320).

FORPE trial is the first report of the non-immunogenic staphylokinase usage in patients with massive pulmonary embolism accompanied by unstable haemodynamics. Non-immunogenic staphylokinase was found to be non-inferior to alteplase (p=1.00). Non-immunogenic staphylokinase had high safety profile and did not cause the major bleeding. No cases of haemorrhagic stroke or major bleeding were recorded in the non-immunogenic staphylokinase group, whereas there were five cases (5%) of BARC type 3+5 bleedings in the alteplase group (p=0.026). All major bleedings and fatal intracranial haemorrhage in the alteplase group were registered only in 60 years old patients.

The unique mechanism of action of non-immunogenic staphylokinase allows it to be used in a single dose of 15 mg, regardless of the patient's body weight. Non-immunogenic staphylokinase is easy to administer with a rapid single bolus that makes it convenient for use in emergency medicine.

The indication "massive pulmonary embolism" is included in the Instructions for medical use of the non-immunogenic staphylokinase. In routine clinical practice, the non-immunogenic staphylokinase is used for massive pulmonary embolism treatment since 2024.

The aim of FORPE Registry is to study the safety and efficacy of the non-immunogenic staphylokinase in patients with massive pulmonary embolism in routine clinical practice.

Inclusion Criteria:

• Men and women aged 18 years and older.
• Verified diagnosis of massive pulmonary embolism (using computer tomography)
• Signs of overload / dysfunction of the right ventricle (at least one) in combination with persistent arterial hypotension or shock
• The time from the symptoms onset is no more than 14 days.
• Thrombolysis with the non-immunogenic staphylokinase, 15 mg as a single intravenous bolus.

Exclusion Criteria:

• 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.