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

NCT ID: NCT07146360

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-25
• Study Completion Date: 2017-12-11

Brief Summary

Thi is is a multi-center, randomized, single-blind, parallel group clinical trial to evaluate the efficacy and safety of the intravenious thrombolysis with Revelise® (GENERIUM, Russia) in comparosin with the Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany) in patients with acute myocardial infarction (MI) with ST-segment elevation on the electrocardiogram (ECG). The thrombolisis was performed within the period of up to 6 hours and from 6 to 12 hours from the MI symptoms onset.

Detailed Description

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.

Conditions

Myocardial Infarction (MI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Revelise® (GENERIUM, Russia)

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Group Type: EXPERIMENTAL

Revelise (GENERIUM, Russia)

Intervention Type: BIOLOGICAL

1. 90-minute accelerated dosing regimen for patients who can start treatment within 6 hours after the onset of symptoms of acute myocardial infarction (AMI): Initial bolus injection: 15 mg intraveniously (IV) followed by an infusion of 50 mg over 30 minutes and then a subsequent infusion of 35 mg over 60 minutes to reach a maximum total dose of 100 mg.

• For patients less than 65 kg: Initial bolus injection: 15 mg IV - 0.75 mg/kg (maximum 50 mg) over 30 minutes followed by an additional infusion of 0.5 mg/kg (maximum 35 mg) over 60 minutes.

2. 3-hour dosing regimen for patients who can start treatment between 6 and 12 hours after symptom onset of AMI: Initial bolus injection: 10 mg IV followed by an infusion of 50 mg over 60 minutes and then a subsequent infusion of 40 mg over 120 minutes to achieve a maximum total dose of 100 mg.

• For patients less than 65 kg: The cumulative dose should not exceed 1.5 mg/kg.

Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany)

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Group Type: ACTIVE_COMPARATOR

Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany)

Intervention Type: BIOLOGICAL

1. 90-minute accelerated dosing regimen for patients who can start treatment within 6 hours after the onset of symptoms of acute myocardial infarction (AMI): Initial bolus injection: 15 mg intraveniously (IV) followed by an infusion of 50 mg over 30 minutes and then a subsequent infusion of 35 mg over 60 minutes to reach a maximum total dose of 100 mg.

• For patients less than 65 kg: Initial bolus injection: 15 mg IV - 0.75 mg/kg (maximum 50 mg) over 30 minutes followed by an additional infusion of 0.5 mg/kg (maximum 35 mg) over 60 minutes.

2. 3-hour dosing regimen for patients who can start treatment between 6 and 12 hours after symptom onset of AMI: Initial bolus injection: 10 mg IV followed by an infusion of 50 mg over 60 minutes and then a subsequent infusion of 40 mg over 120 minutes to achieve a maximum total dose of 100 mg.

• For patients less than 65 kg: The cumulative dose should not exceed 1.5 mg/kg.

Interventions

Revelise (GENERIUM, Russia)

1. 90-minute accelerated dosing regimen for patients who can start treatment within 6 hours after the onset of symptoms of acute myocardial infarction (AMI): Initial bolus injection: 15 mg intraveniously (IV) followed by an infusion of 50 mg over 30 minutes and then a subsequent infusion of 35 mg over 60 minutes to reach a maximum total dose of 100 mg.

• For patients less than 65 kg: Initial bolus injection: 15 mg IV - 0.75 mg/kg (maximum 50 mg) over 30 minutes followed by an additional infusion of 0.5 mg/kg (maximum 35 mg) over 60 minutes.

2. 3-hour dosing regimen for patients who can start treatment between 6 and 12 hours after symptom onset of AMI: Initial bolus injection: 10 mg IV followed by an infusion of 50 mg over 60 minutes and then a subsequent infusion of 40 mg over 120 minutes to achieve a maximum total dose of 100 mg.

• For patients less than 65 kg: The cumulative dose should not exceed 1.5 mg/kg.

Intervention Type: BIOLOGICAL

Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany)

1. 90-minute accelerated dosing regimen for patients who can start treatment within 6 hours after the onset of symptoms of acute myocardial infarction (AMI): Initial bolus injection: 15 mg intraveniously (IV) followed by an infusion of 50 mg over 30 minutes and then a subsequent infusion of 35 mg over 60 minutes to reach a maximum total dose of 100 mg.

• For patients less than 65 kg: Initial bolus injection: 15 mg IV - 0.75 mg/kg (maximum 50 mg) over 30 minutes followed by an additional infusion of 0.5 mg/kg (maximum 35 mg) over 60 minutes.

2. 3-hour dosing regimen for patients who can start treatment between 6 and 12 hours after symptom onset of AMI: Initial bolus injection: 10 mg IV followed by an infusion of 50 mg over 60 minutes and then a subsequent infusion of 40 mg over 120 minutes to achieve a maximum total dose of 100 mg.

• For patients less than 65 kg: The cumulative dose should not exceed 1.5 mg/kg.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age between 18 and 80 years

2. 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).

3. Written informed consent of the patient for participation in the trial and conduction of coronary angiography.

Exclusion Criteria

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

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

6. 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.

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

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

9. 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.

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

12. 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).

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

15. 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.

17. 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.

20. Pregnancy or lactation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AO GENERIUM

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Oksana A. Markova, MD

Role: STUDY_CHAIR

Locations

Regional State Budgetary Healthcare Institution "Altai Regional Cardiological Dispensary"

Barnaul, Altayskiy Kray, Russia

City Budgetary Healthcare Institution of Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich"

Arkhangelsk, Arkhangelskaya oblast, Russia

SBHI Republican Cardiology Center

Ufa, Bashkortostan Republic, Russia

State Budgetary Healthcare Institution of Novosibirsk "City Clinical Hospital No. 2"

Novosibirsk, Novosibirsk Oblast, Russia

Municipal Health Care Institution City Clinical Hospital No.4

Perm, Perm Krai, Russia

FSBEI of HVE Mordovia State University named after N.P. Ogarev, Medical Institute, SBHI MR "City Clinical Hospital No. 3"

Saransk, Respublika Mordoviya, Russia

Federal State Budgetary Scientific Institution "Scientific Research Institute for Complex Issues of Cardiovascular Diseases"

Kemerovo, , Russia

SBHI "State Budgetary Healthcare Institution of MHD"

Moscow, , Russia

Moscow City State Budgetary Healthcare Institution "Filatov City Clinical Hospital No. 15 of Moscow Healthcare Department"

Moscow, , Russia

State Budgetary Healthcare Institution of the city of Moscow "City Clinical Hospital No. 64 of Moscow Healthcare Department"

Moscow, , Russia

Federally Funded Higher Education Institution "Russian National Research Medical University named after N.I. Pirogov" of the Ministry of Health of the Russian Federation

Moscow, , Russia

Moscow City State Budgetary Healthcare Institution "Botkin City Clinical Hospital of Moscow Healthcare Department"

Moscow, , Russia

SBHI "CCH No. 81 MHD"

Moscow, , Russia

SBHI "Sklifosovsky Research Institute of Emergency Medicine of MHD"

Moscow, , Russia

Novosibirsk Region State Budgetary Healthcare Institution "City Clinical Hospital No. 1"

Novosibirsk, , Russia

Novosibirsk Region State Budgetary Healthcare Institution "City Clinical Hospital No. 34"

Novosibirsk, , Russia

Municipal Budgetary Healthcare Institution "City Emergency Medical Hospital of Rostov-on-Don"

Rostov-on-Don, , Russia

SI "St. Petersburg Dzhanelidze Research Institute of Emergency Medicine"

Saint Petersburg, , Russia

St. Petersburg State Budgetary Healthcare Institution "Pokrovskaya City Hospital"

Saint Petersburg, , Russia

FSI Saratov Research Institute of Cardiology of Russian medical Technologies

Saratov, , Russia

State Healthcare Institution "City Clinical Hospital No. 12"

Saratov, , Russia

SBHI SC "Stavropol Regional Clinical Hospital"

Stavropol, , Russia

Countries

Russia

Related Links

https://therapy-journal.ru/articles/Sravnitelnoe-issledovanie-effektivnosti-i-bezopasnosti-otechestvennogo-rekombinantnogo-tkanevogo-aktivatora-plazminogena-Reveliza-u-bolnyh-infarktom-m.html

Milto A.S., Kokorin V.A., Markova O.A. et. al. Comparative safety and efficacy study of Russian recombinant tissue plazminogen activator Revelisa® in patients with myocardial infarction. Therapy, 2019; 2 \[28\]:42-56

Other Identifiers

REV-STEMI-III

Identifier Type: -

Identifier Source: org_study_id