Study of Efficacy and Safety of GNR-060 vs Metalyse in Patients With ST Elevation Myocardial Infarction
Study Details
Study Description
Brief Summary
GNR-060(JSC "GENERIUM", Russia) is a proposed biosimilar to the referent product Metalyse. This study is to compare the clinical efficacy and safety of GNR-060 vs Metalyse as a thrombolitic agent in patients with with ST Elevation Myocardial Infarction (STEMI).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The trial is designed as a multicenter randomized single blinded study with the centralized blinded outcome assessment. The patients with diagnosed STEMI will be randomly assigned with one of the treatment options within 4 hours after the symptoms onset. The effectiveness of the tested product GNR-060 or reference product Metalyze will be assessed by the coronarography within 24 hours after the thrombolysis with the following PCI in case of ineffectiveness. The patients will then be followed up for survival and cardiac events for 90 days. The safety assessment will also include any related hemorrhagic complication. The pharmacokinetic parameters and immunogenicity will be also assessed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GNR-060 Main group (122 patients) - GNR-060 |
Biological: GNR-060
GNR-060 will be administered in an individual dose depending on body weight as a single intravenous bolus
Other Names:
|
| Active Comparator: Metalyse Control group (122 patients) - Metalyse |
Biological: Metalyse
Metalyse will be administered in an individual dose depending on body weight as a single intravenous bolus
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Frequency of the complete myocardial reperfusion based on the independent assessment of coronary angiography [up to 24 hours]
TIMI Grade 3 coronary blood flow after the trombolisis
Secondary Outcome Measures
- Frequency of the complete+partial myocardial reperfusion based on the independent assessment of coronary angiography [up to 24 hours]
TIMI Grade 2 or 3 coronary blood flow after the trombolisis
- Frequency of myocardial reperfusion based on ECG data [after 90 minutes]
Resolution of the ST segment by 30%, 50%, 70% or more
- Changes in troponin T and creatine kinase MB levels [7 days]
- 90-Day mortality [90 days]
Mortality within 90 days after myocardial infarction
- 30-Day and 90-Day cardiovascular mortality [30 and 90 days]
Cardiovascular mortality up to 30 and 90 days after myocardial infarction
- Frequency of the postinfarction complications [up to 30 days]
Frequency of any postifarction complication except for arrythmias
- Frequency of the combined events "cardiovascular death + recurrent myocardial infarction + stroke" and "cardiovascular death + recurrent myocardial infarction + stroke + heart failure" [30 days]
Other Outcome Measures
- Frequency and severity of hemorrhagic complications [up to 30 days]
Hemorragies will be classified based on BARC, ISTH and TIMI definitions
- Incidence of the hemorrhagic stroke [up to 30 days]
Any case of treatment-related hemorrhagic stroke
- Frequency and severity of the adverse drug reactions [up to 30 days]
Any adverse events related to the trombolisis
- Proportion of patients with the antidrug antibodies [7 days]
Anti-tenecteplaze antibody will be measured before trombolisis and 7 days after.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Myocardial infarction with elevation of the ST segment of the ECG (at point J) in 2 adjacent leads after no more than 6 hours from the onset of pain (lasting at least 20 minutes) in the chest (at the time of screening):
-
≥ 2.5 mm in male ˂ 40 years, ≥ 2 mm in male ≥ 40 years, or ≥ 1.5 mm in female in leads V2-V3 and/or
-
≥ 1 mm in other leads in the absence of left ventricular hypertrophy or left bundle branch block.
Exclusion Criteria:
-
Diseases accompanied by significant bleeding, currently or within the last 6 months, hemorrhagic diathesis.
-
Current oral anticoagulant therapy with INR > 1.3.
-
Diseases of the central nervous system at present or in history (neoplasm, aneurysm, surgery on the brain or spinal cord).
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Severe uncontrolled arterial hypertension.
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Major surgical interventions, biopsy of a parenchymal organ or significant trauma within the last 2 months (including trauma in combination with AMI at the present time), recent (within the last 3 months) traumatic brain injury.
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Prolonged or traumatic cardiopulmonary resuscitation (> 2 minutes) within the last 2 weeks.
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Severe liver dysfunction, including liver failure, cirrhosis, portal hypertension (including esophageal varicose veins), active hepatitis.
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Peptic ulcer of the stomach or duodenum in the acute stage.
-
Chronic kidney disease or other significant kidney disease with a decrease in glomerular filtration rate ≤30 ml / min / 1.73 m2.
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Arterial aneurysm or presence of arterial/venous vascular malformation.
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Neoplasm with an increased risk of bleeding.
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Acute pericarditis and/or subacute bacterial endocarditis.
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Acute pancreatitis.
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Hypersensitivity to the active substance (tenecteplase), gentamicin (residual traces of the manufacturing process) or any excipient.
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Hemorrhagic stroke or stroke of unknown etiology at present or in history.
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Intracranial (including subarachnoid) hemorrhage at present or in history.
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Ischemic stroke or transient ischemic attack (TIA) within the last 6 months.
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Recent bleeding from the gastrointestinal or genitourinary tract or childbirth (within the last 10 days).
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A recent (before 24 hours) puncture of an incompressible blood vessel (eg, subclavian or jugular vein).
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Congenital and hereditary hemorrhagic coagulopathy (hemophilia, etc.) in history.
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Pregnancy or breastfeeding.
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Body mass index (BMI) less than 18.5 or more than 40 kg/m2.
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Participation in another clinical trial currently or within 30 days prior to screening; use of any investigational drug within 30 days or 5 half-lives prior to screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Regional State Budgetary Health Institution "Regional Clinical Emergency Hospital" | Barnaul | Altai Territory | Russian Federation | 656038 |
| 2 | Regional State Budgetary Institution of Health Care "Altai Territorial Cardiology Dispensary" | Barnaul | Altai Territory | Russian Federation | 656055 |
| 3 | State Budgetary Institution of Health Care of the Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich" | Arkhangel'sk | Arkhangelsk Region | Russian Federation | 163001 |
| 4 | Regional State Budgetary Health Institution "Belgorod Regional Clinical Hospital of St. Joasaph" | Belgorod | Belgorod Region | Russian Federation | 308007 |
| 5 | State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4" | Perm | Perm Territory | Russian Federation | 614107 |
| 6 | State Autonomous Healthcare Institution "Interregional Clinical and Diagnostic Center" | Kazan | Republic Of Tatarstan | Russian Federation | 420101 |
| 7 | Municipal budgetary health care institution "City emergency hospital of the city of Rostov-on-Don" | Rostov-on-Don | Rostov Region | Russian Federation | 344068 |
| 8 | State Budgetary Institution of the Ryazan Region "Regional Clinical Hospital" | Ryazan' | Ryazan Region | Russian Federation | 390039 |
| 9 | State budgetary health care institution of the Sverdlovsk region "Scientific and practical center for specialized types of medical care" Ural Institute of Cardiology " | Ekaterinburg | Sverdlovsk Region | Russian Federation | 620144 |
| 10 | State Health Institution "City Clinical Emergency Hospital No. 25" | Volgograd | Volgograd Region | Russian Federation | 400138 |
| 11 | State Budgetary Health Institution of the Yaroslavl Region "Regional Clinical Hospital" | Yaroslavl | Yaroslavl Region | Russian Federation | 150062 |
Sponsors and Collaborators
- AO GENERIUM
Investigators
- Study Chair: Oksana A. Markova, MD, MSc, AO GENERIUM
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TNP-STEMI-III
- № 142 eff. date 17 March 2021