A Phase III Trial to Assess the Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Acute Ischaemic Stroke in 4.5 Hours After Stroke Onset
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,552
- 试验地点
- 72
- 主要终点
- The proportion of patients with excellent functional outcome at 90 days
研究概览
简要总结
Intravenous thrombolysis is the first-line therapy in patients with acute ischemic stroke within 4·5 hours of symptom onset, and recombinant tissue plasminogen activator (alteplase) is the preferred thrombolytic agent for this purpose.
RhPro-UK is a specific plasminogen activator. rhPro-UK only acts on occlusive thrombus and has little effect on hemostatic thrombus. In addition, rhPro-UK does not form covalent complexes with protease inhibitors in plasma, so the concentrations of rhpro-UK and protease inhibitors in the blood do not decrease compared with alteplase. Therefore, rhPro-UK therapies have a potential advantage of less systemic bleeding in treated subjects. Data from several previous studies suggest that rhPro-UK is efficacious when used to treat patients with acute myocardial infarction. On April 2, 2011, rhPro-UK injection was approved by the National Medical Products Administration to treat acute myocardial infarction. Since then, rhPro-UK has been widely used to treat myocardial infarction in China.
Since 2016, a phase 2 clinical trial was carried to explore the dosing of rhPro-UK in patients with acute ischemic stroke, followed by another study with a sample size of 680 patients to initially validate the efficacy and safety of the proposed dose of 35mg. The results of these studies suggested that rhPro-UK was effective, and there were no safety concerns. To further prove the efficacy and safety of rhPro-UK in patients with acute ischemic stroke, investigators conducted this phase 3 study (PROST-2).
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 (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).
- •18 years or older, male or female.
- •NIH Stroke Scale（NIHSS）scores of 4 to
- •Treatment within 4.5 hours after stroke onset.
- •The symptoms of stroke last at least 30 minutes without significant improvement before treatment.
- •Informed consent by patient or by patient's guardians.
排除标准
- •Prestroke modified rankin scale of ≥
- •Large areas of hypodense ischaemic changes on baseline CT（Infarction area> 1/3 of the middle cerebral artery feeding area）.
- •Intracranial hemorrhage.
- •Previous history of intracranial hemorrhage.
- •Severe cerebral trauma or stroke history within 3 months.
- •Intracranial tumor or giant intracranial aneurysm.
- •Intracranial or intraspinal surgery within the past 3 months.
- •Gastrointestinal or urinary bleeding within the past 3 weeks.
- •History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation).
- •Puncture in 1 week which can not be oppressed.
- •Active visceral hemorrhage.
- •Aortic arch dissection.
- •Bacterial endocarditis or pericarditis.
- •Planned for thrombectomy.
- •Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment.
- •High risk of acute hemorrhage include platelet count<10^9/L.
- •Received low molecular weight heparin or heparin within 24 hours.
- •Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours.
- •Using of oral anticoagulant drugs and PT >15s or INR >1.
- •Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke.
- •Blood glucose < 2.8 mmol/L or > 22.2 mmol/L.
- •Allergies to rhPro-UK or rt-PA active ingredients or other components.
- •Pregnant women or beastfeeding women.
- •Participants in other clinical trials within the past month.
- •The investigator believes that the patient is not suitable for the study.
研究组 & 干预措施
rhPro-UK
Recombinant Human Pro-urokinase (rhPro-UK)
干预措施: rhPro-UK (Drug)
rt-PA
Alteplase(rt-PA)
干预措施: rt-PA (Drug)
结局指标
主要结局
The proportion of patients with excellent functional outcome at 90 days
时间窗: 90±7 days
A score of 0 or 1 on the modified Rankin scale(which ranges from 0 \[no symptoms\] to 6 \[death\]) at 90 days indicated an excellent functional outcome.
次要结局
- The proportion of patients with neurological improvement at 24 hours(22-36 hours)
- Self-care ability in daily life(90±7 days)
- The proportion of patients with independent functional outcome at 90 days(90±7 days)
- Functional handicap(90±7 days)
- The change of neurological function at 7 days(7 ±2 days)
- Any intracranial hemorrhage(7 days)
- Any systematic bleeding event（defined as ISTH）(7 days)
- The change of neurological function at 24 hours(22-36 hours)
- All-cause death within 7 days(7 days)
- All-cause death within 90 days(90 days)
- Symptomatic intracranial hemorrhage defined as SITS-MOST(22-36 hours)
- The proportion of patients with neurological improvement at 7 days(7 ±2 days)
- Symptomatic intracranial hemorrhage defined as ECASSIII(7 days)