Efficacy and Safety Study of Proposed Biosimilar Product Reveliza vs Actilise in Patients With ST-segment Elevation Myocardial Infarction

Revelise®, lyophilizate for solution for infusion, 50 mg, is the proposed biosimilar recombinant human tissue plasminogen activator developed by GENERIUM JSC (Russia).

All the patients with acute myocardial infurction, enrolled into the study, have been randomised to receive either biosimilar product or a reference produc. The stratification factor was the time from the MI symptoms onset: 1) within the 6 hours and 2) from 6 to 12 hours. Each patient was then followed-up for 3 months, including up to 14 days in an inpatient facility. Coronary angiography was to be performed within the first 24 hours after the administration of the study products, but not earlier than 3 hours after beginning of infusion in case of confirmed thrombolysis (onset of myocardial reperfusion) and immediately - in the absence of reperfusion according to ECG data (ST-segment reduction by less than 50% afterthe infusion start). The patients' condition will be assessed at the scheduled visits.

Inclusion criteria

• Age between 18 and 80 years
• Acute myocardial infarction with ST-segment elevation on ECG (point J) in 2 or more consecutive leads of more than 0.2 mV in men or more than 0.15 mV in women in leads V2-V3 or more than 0.1 mV in other leads after not more than 12 hours from pain onset (lasting at least 20 minutes) in chest (at the time of screening).
• Written informed consent of the patient for participation in the trial and conduction of coronary angiography.

Exclusion criteria

• Significant bleeding at present or during the previous 6 months, hemorrhagic diathesis.

• Congenital-hereditary hemorrhagic coagulopathy (hemophilia, etc.) in medical history 5. Concomitant administration of oral anticoagulants, for example, warfarin (INR > 1.3).

• Surgery of the brain or spinal cord, neoplasms of the brain or spinal cord in past medical history, traumatic brain injury during the last 3 months.

• Intracranial (including subarachnoid) hemorrhage currently or in past medical history.

• Hemorrhagic stroke or stroke of unknown etiology in the anamnesis, suspected hemorrhagic stroke.

• Ischemic stroke or transient ischemic attack during the last 6 months. 10. Severe (systolic blood pressure higher than 185 mmHg or diastolic blood pressure higher than 110 mmHg) uncontrolled hypertension.

• Extensive surgery or significant trauma during the previous 3 weeks (including any injury combined with this acute myocardial infarction).

• Long-term or traumatic cardiopulmonary resuscitation (>2 min), delivery during the previous 10 days; recently performed puncture of an incompressible blood vessel (for example, subclavian or jugular vein).

• Bacterial endocarditis, pericarditis. 14. Known arterial aneurysms, defects in arteries or veins' development, suspected aortic dissection.

• Confirmed gastric ulcer or duodenal ulcer during the last 3 months. 16. Known severe liver diseases, including liver failure, cirrhosis, portal hypertension (including esophageal varicose veins dilatation), active hepatitis.

• Acute pancreatitis. 18. Known neoplasm with an increased risk of bleeding. 19. Hypersensitivity to the components of the product, allergic reactions to gentamicin in past medical history.

• Pregnancy or lactation.