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

NCT07146360 | Completed Phase 3 DMC

• 1 other identifier: REV-STEMI-III
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 22

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.

Conditions

Myocardial Infarction (MI)

Keywords

Acute Myocardial Infarction; Thrombosis; Recombinant tissue plasminogen activator; Acute Coronary Syndrome; Coronary Syndrome; Chronic heart failure; Activated partial thromboplastin time; New York Heart Association; Thrombolytic therapy

Outcome Measures

Primary Outcomes (1)

• Myocardial reperfusion rate confirmed by the coronary angiography (CAG)

  Myocardial reperfusion confirmed by the CAG: coronary blood flow TIMI 3 or 2 degrees are considered to be myocardial reperfusion. Grade 3 - normal coronary perfusion: antegrade blood flow and contrast washout distal to the site of obstruction do not differ from those in an unaffected vessel; grade 2 - incomplete coronary perfusion: complete contrasting of the coronary artery distal to the site of obstruction, however, there is a delay in filling of the distal bed or slowdown in contrast washout).

  In 3 hours after the beginning of IV thrombolysis in case of ECG data of successful reperfusion and immediately - if there is no effect of thrombolysis based on ECG data.

Secondary Outcomes (9)

• Frequency of percutaneous coronary intervention (PCI)

  During the first day after the intravenous thrombolysis, but not earlier than 3 hours after the start of the infusion in case of coronary reperfusion and immediately in case of nocoronary thrombolysis based on ECG data

• Cardiovascular mortality

  Up to 30 days after acute myocardial infarction

• Myocardial reperfusion rate according to ECG data.

  90 or 180 minutes after the beginning of the IV thrombolysis.

• Overall mortality

  Up to 90 days

• Incidence of post-infarction complications

  30 days

Study Arms (2)

Revelise® (GENERIUM, Russia)

EXPERIMENTAL

аlteplase

Biological: Revelise (GENERIUM, Russia)

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

ACTIVE COMPARATOR

аlteplase

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

Interventions

Revelise (GENERIUM, Russia) 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.

Revelise® (GENERIUM, Russia)

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (22)

Regional State Budgetary Healthcare Institution "Altai Regional Cardiological Dispensary"

Barnaul, Altayskiy Kray, 656055, Russia

Location

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

Arkhangelsk, Arkhangelskaya oblast, 163001, Russia

Location

SBHI Republican Cardiology Center

Ufa, Bashkortostan Republic, 450106, Russia

Location

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

Novosibirsk, Novosibirsk Oblast, 630051, Russia

Location

Municipal Health Care Institution City Clinical Hospital No.4

Perm, Perm Krai, 614107, Russia

Location

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

Saransk, Respublika Mordoviya, 430005, Russia

Location

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

Kemerovo, 650002, Russia

Location

SBHI "State Budgetary Healthcare Institution of MHD"

Moscow, 101000, Russia

Location

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

Moscow, 111539, Russia

Location

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

Moscow, 117292, Russia

Location

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, 117997, Russia

Location

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

Moscow, 125284, Russia

Location

SBHI "CCH No. 81 MHD"

Moscow, 127644, Russia

Location

SBHI "Sklifosovsky Research Institute of Emergency Medicine of MHD"

Moscow, 129090, Russia

Location

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

Novosibirsk, 630047, Russia

Location

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

Novosibirsk, 630054, Russia

Location

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

Rostov-on-Don, 344068, Russia

Location

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

Saint Petersburg, 192242, Russia

Location

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

Saint Petersburg, 199106, Russia

Location

FSI Saratov Research Institute of Cardiology of Russian medical Technologies

Saratov, 410028, Russia

Location

State Healthcare Institution "City Clinical Hospital No. 12"

Saratov, 410039, Russia

Location

SBHI SC "Stavropol Regional Clinical Hospital"

Stavropol, 355000, Russia

Location

Related Links

• 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

MeSH Terms

Conditions

Myocardial Infarction; Thrombosis; Acute Coronary Syndrome; Angina, Unstable

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Embolism and Thrombosis; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Oksana A. Markova, MD

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 28, 2025
• Study Start: May 25, 2014
• Primary Completion: November 21, 2017
• Study Completion: December 11, 2017
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

RU (22)