Overview
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).
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.
Eligibility
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).
- Severe uncontrolled arterial hypertension.
- 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.
- Prolonged or traumatic cardiopulmonary resuscitation (> 2 minutes) within the last 2 weeks.
- Severe liver dysfunction, including liver failure, cirrhosis, portal hypertension (including esophageal varicose veins), active hepatitis.
- 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.
- Arterial aneurysm or presence of arterial/venous vascular malformation.
- Neoplasm with an increased risk of bleeding.
- Acute pericarditis and/or subacute bacterial endocarditis.
- Acute pancreatitis.
- Hypersensitivity to the active substance (tenecteplase), gentamicin (residual traces of the manufacturing process) or any excipient.
- Hemorrhagic stroke or stroke of unknown etiology at present or in history.
- Intracranial (including subarachnoid) hemorrhage at present or in history.
- Ischemic stroke or transient ischemic attack (TIA) within the last 6 months.
- Recent bleeding from the gastrointestinal or genitourinary tract or childbirth (within the last 10 days).
- A recent (before 24 hours) puncture of an incompressible blood vessel (eg, subclavian or jugular vein).
- Congenital and hereditary hemorrhagic coagulopathy (hemophilia, etc.) in history.
- Pregnancy or breastfeeding.
- Body mass index (BMI) less than 18.5 or more than 40 kg/m2.
- 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.