A Multi-center, Randomized, Single-blind, Parallel Group Clinical Trial to Evaluate the Efficacy and Safety of the Revelise® (GENERIUM, Russia) as Compared With the Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany) in Patients With Acute Myocardial Infarction With ST-segment Elevation on ECG
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AO GENERIUM
- 入组人数
- 180
- 试验地点
- 22
- 主要终点
- Myocardial reperfusion rate confirmed by the coronary angiography (CAG)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •1. Significant bleeding at present or during the previous 6 months, hemorrhagic diathesis.
- •4. Congenital-hereditary hemorrhagic coagulopathy (hemophilia, etc.) in medical history
- •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.
- •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.
- •Known arterial aneurysms, defects in arteries or veins' development, suspected aortic dissection.
- •15. Confirmed gastric ulcer or duodenal ulcer during the last 3 months.
- •Known severe liver diseases, including liver failure, cirrhosis, portal hypertension (including esophageal varicose veins dilatation), active hepatitis.
- •17. Acute pancreatitis.
- •Known neoplasm with an increased risk of bleeding.
- •Hypersensitivity to the components of the product, allergic reactions to gentamicin in past medical history.
- •20. Pregnancy or lactation.
研究组 & 干预措施
Revelise® (GENERIUM, Russia)
аlteplase
干预措施: Revelise (GENERIUM, Russia) (Biological)
Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany)
аlteplase
干预措施: Actilyse® (Boehringer Ingelheim Pharma GmbH and Co.KG, Germany) (Biological)
结局指标
主要结局
Myocardial reperfusion rate confirmed by the coronary angiography (CAG)
时间窗: 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.
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).
次要结局
- 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)
- Incidence of the combined cardiovascular events(Within 30 and 90 days)
- Troponin changes(14 days)
- Fibrinogen concentration(Days 1, 2 and 3)
- D-dimer concentration(Days 1, 2 and 3)