Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Recombinant Human TNK Tissue-Type Plasminogen Activator for Injection (rhTNK-tPA, Mingfule) in Intravenous Thrombolysis for Acute Ischemic Stroke With Extended Time Window (4.5-24 Hours After Onset).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 890
- 试验地点
- 1
- 主要终点
- The proportion of participants with a score of 0-1 on the modified Rankin Scale (mRS)
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical study designed to evaluate the efficacy of recombinant human tissue-type plasminogen activator variant (rhTNK-tPA) (0.25 mg/kg, maximum dose 25 mg) compared with placebo in patients with acute large vessel occlusive stroke who present within 4.5 to 24 hours of symptom onset. The study plans to enroll patients with acute large vessel occlusive stroke who present within 4.5 to 24 hours of symptom onset (including wake-up strokes and strokes without witnesses). A centralized 1:1 randomization will be adopted, and eligible participants will be randomly assigned to two groups: the experimental group will receive rhTNK-tPA at a dose of 0.25 mg/kg, while the placebo group will receive rhTNK-tPA placebo.
详细描述
This multicenter, randomized, double-blind, placebo-controlled Phase III clinical study aims to evaluate the efficacy of recombinant human tissue-type plasminogen activator variant (rhTNK-tPA) (0.25 mg/kg, maximum dose 25 mg) compared with placebo in patients with acute large vessel occlusive stroke who present within 4.5 to 24 hours of symptom onset. The study initially planned to enroll 890 patients, who would be randomly assigned to the experimental group (rhTNK-tPA group) or the control group (placebo group) at a 1:1 ratio. After an unblinded sample size re-estimation during the interim analysis, the maximum sample size could be adjusted to 1,300 patients.
Key characteristics of the primary study population include: age ≥ 18 years; time from symptom onset to treatment ranging from 4.5 hours to 24 hours; occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery confirmed by computed tomography angiography (CTA)/magnetic resonance angiography (MRA), which is the responsible vessel for the signs and symptoms of acute ischemic stroke; modified Rankin Scale (mRS) score ≤ 1 before symptom onset; baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 6; and presence of target mismatch on computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) combined with magnetic resonance perfusion (MRP) (ischemic core volume < 70 mL, mismatch ratio ≥ 1.8, and mismatch volume ≥ 15 mL). Patients with a known allergy to rhTNK-tPA and those with contraindications to thrombolysis were excluded.
The entire study duration is approximately 90 days, including the screening period, treatment period, and follow-up period. The primary study endpoint is the proportion of participants with a modified Rankin Scale (mRS) score of 0-1 at the 90-day follow-up.
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
- Triple (Care Provider, Investigator, 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
- •Aged ≥ 18 years, regardless of gender;
- •Time from symptom onset to treatment is 4.5 - 24 hours(Including the boundary values.), including patients with wake-up stroke or stroke without witnesses; the time of symptom onset is defined as the "last known normal time";
- •Modified Rankin Scale (mRS) score ≤ 1 before stroke onset;
- •Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 6;
- •Neuroimaging findings: occlusion of the internal carotid artery (ICA), M1 or M2 segment of the middle cerebral artery (MCA) confirmed by computed tomography angiography (CTA)/magnetic resonance angiography (MRA), which is the responsible vessel for the signs and symptoms of acute ischemic stroke; presence of target mismatch on computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) + magnetic resonance perfusion (MRP) (ischemic core volume < 70 mL, mismatch ratio ≥ 1.8, mismatch volume ≥ 15 mL);
- •Voluntary signing of the informed consent form by the participant or their legal guardian.
排除标准
- •Patients with known allergy to recombinant human tissue plasminogen activator (rhTNK-tPA);
- •Patients with an expected life expectancy of less than 1 year;
- •Patients with rapidly improving symptoms (which may indicate spontaneous recanalization), as determined by the investigator;
- •Patients with a score of > 2 on Item 1a (Level of Consciousness) of the National Institutes of Health Stroke Scale (NIHSS), or those who had a seizure at stroke onset, or had hemiplegia after seizure, or had other neurological/psychiatric disorders that rendered them unable or unwilling to cooperate;
- •Severe and persistent hypertension uncontrolled by medication ;
- •Blood glucose < 2.8 mmol/L or > 22.2 mmol/L;
- •Active internal bleeding with a high risk of hemorrhage;
- •Any known coagulation disorder;
- •Known platelet function defect or platelet count less than 100×10⁹/L;
研究组 & 干预措施
Experimental Group
Receive rhTNK-tPA administration at 0.25mg/kg, with the maximum dose not exceeding 25mg.
干预措施: rhTNK-tPA (Drug)
Placebo Group
Receive placebo treatment, administration method and dosage same as rhTNK-tPA
干预措施: Placebo (Drug)
结局指标
主要结局
The proportion of participants with a score of 0-1 on the modified Rankin Scale (mRS)
时间窗: At Day90.
The modified Rankin Scale (mRS) is used to assess the status of neurological function recovery in patients after stroke. By evaluating the independence of patients in daily activities, it classifies functional levels into grades 0-6 (Grade 0 indicates no symptoms at all, Grades 1-5 correspond to functional impairments ranging from mild to severe, and Grade 6 indicates death).
次要结局
- Incidence of symptomatic intracerebral hemorrhage within 36 hours after randomization(36 Hours after Randomization)
- Overall mortality rate at Day 90.(At Day90.)
- Incidence of significant systemic hemorrhage (moderate to severe per GUSTO classification) at Day 90.(At Day90.)
- Proportion of adverse events (AEs)/serious adverse events (SAEs) at Day 90.(At Day90.)
- Modified Rankin Scale (mRS) score at Day 90 (shift analysis).(At Day90.)
- Title: Proportion of participants with mRS score of 0-2 at Day 90.(At Day90.)
- Proportion of participants with an NIHSS score of ≤1 or a reduction of ≥8 points from baseline within 72 hours after randomization.(72 Hours after Randomization.)
- Change in NIHSS score from baseline at Day 7.(At Day7.)
- Rate of favorable reperfusion (90% improvement in Tmax >6s compared with prior status) within 24 hours after randomization.(24 Hours after Randomization.)
- Proportion of participants with a Barthel Index (BI) score of ≥95 at Day 90.(At Day90.)
- Growth of irreversible cerebral infarction volume before treatment and 24 hours after treatment.(72 Hours after Treatment.)
- Proportion of participants with favorable reperfusion (TICI 2b/3 or TICI 3) on angiography before endovascular treatment (limited to participants who received endovascular treatment).(Periprocedural)