Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2): a Prospective, Randomized, Open Label, Blinded Assessment of Outcome, and Multi-center Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- rate of vessel recanalization
研究概览
简要总结
While intravenous thrombolysis (IVT) within 4.5 hours is the standard medical reperfusion therapy, its efficacy is limited, particularly for large or medium vessel occlusions (LVO/MeVO), with low recanalization rates for IVT with rt-PA. The newer thrombolytic agent, tenecteplase (TNK), offers practical advantages-including single bolus administration, a longer half-life, and potentially higher fibrin specificity-and has been shown to be non-inferior to rt-PA.
Despite advances, a significant proportion of patients with LVO/MeVO do not achieve early clinical improvement after standard IVT, likely due to persistent occlusion from a high thrombus burden. Endovascular therapy, while highly effective for LVO, has limited accessibility. Therefore, there is an urgent need for more effective and widely accessible pharmacological strategies.
This study proposes a rescue strategy based on the hypothesis that a second dose of IVT may improve outcomes in patients with imaging-confirmed LVO or MeVO who show no significant neurological improvement one hour after standard TNK thrombolysis (administered within 4.5 hours of stroke onset). The primary aim of this study is to formally evaluate the efficacy and safety of a repeated dose of intravenous tenecteplase in this specific patient population.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 year;
- •Acute ischemic stroke presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received standard-dose intravenous thrombolysis, and with no planned thrombectomy;
- •Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
- •Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI);
- •No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis;
- •Follow-up imaging (CTA or MRA) at 1 hour after the first thrombolysis rules out intracranial hemorrhage and confirms the presence of large or medium vessel occlusion (internal carotid artery, M1-M3 segments of the middle cerebral artery, A1-A3 segments of the anterior cerebral artery, P1-P3 segments of the posterior cerebral artery, basilar artery or V4 segment of the vertebral artery, PICA, AICA, or SCA);
- •The second intravenous thrombolysis can be administered within 6 hours of onset;
- •First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
- •Signed informed consent.
排除标准
- •Planed for endovascular treatment;
- •Significant white matter hyperintensities (Fazekas score 3);
- •Any coagulation abnormality before the first thrombolysis, including INR > 1.5;
- •Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.；
- •Pregnancy；
- •Allergy to the investigational drug(s)；
- •Comorbidity with other serious diseases;
- •Participating in other clinical trials within 3 months;
- •Patients not suitable for the study considered by researcher.
研究组 & 干预措施
Control group
no tenecteplase
TNK group
Tenecteplase is administered intravenously at a dose of 16 mg, with a maximum dose of 0.25 mg/kg.
干预措施: Tenecteplase (Drug)
结局指标
主要结局
rate of vessel recanalization
时间窗: 24 (-6/+12) hours
次要结局
- occurence of major systemic bleeding event(24 (-6/+12) hours)
- occurence of any bleeding event(24 (-6/+12) hours)
- proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)(90±7 days)
- proportion of favorable functional outcome (modified Rankin Scale (mRS) 0-2)(90±7 days)
- occurence of any intracranial hemorrhage(24 (-6/+12) hours)
- ordinal distribution of modified Rankin Scale (mRS)(90±7 days)
- occurrence of early neurological improvement (ENI)(24 (-6/+12) hours)
- change in National Institute of Health stroke scale (NIHSS) score(24 (-6/+12) hours)
- change in National Institute of Health stroke scale (NIHSS) score(10±2 days)
- all-cause mortality(10±2 days)
- occurence of symptomatic intracranial hemorrhage (sICH)(24 (-6/+12) hours)
研究者
Hui-Sheng Chen
Director
General Hospital of Shenyang Military Region