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

Inclusion Criteria:

• Men and women aged 18 and over.

• Verified diagnosis of intermediate high-risk PE using CTPA, no more than two weeksfrom the symptoms onset.

• RV dysfunction, defined as a RV/LV ventricular end-diastolic diameter ratio morethan 1.0 assessed by CTPA.

• Increased risk of early death or hemodynamic collapse, defined by one of thefollowing criteria:

1. systolic blood pressure less than 110 mm Hg, but not less than 90 mm Hg formore than 15 minutes;

2. respiratory rate more than 20 per minute or SpO2 less than 90% without oxygensupport;

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 3weeks after:

• women who have a negative pregnancy test and use the following contraceptives:intrauterine devices, oral contraceptives, contraceptive patch, prolongedinjectable contraceptives, double barrier method of contraception. Women whoare 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 notfertile (documented conditions: vasectomy, infertility).

• Availability of signed and dated informed consent of the patient to participate inthe 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 jugularvein);

• 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 ofidarucizumab;

• 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 ahigh risk of bleeding.

• Lactation, pregnancy.

• Known hypersensitivity to mon-immunogenic recombinant staphylokinase.