A Multicentre, Prospective, Randomized, Open Label, Blinded-endpoint Trial to Optimize the Use of Intravenous Tenecteplase in Participants with Acute Ischemic Stroke (ACT-WHEN)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 4,000
- 试验地点
- 28
- 主要终点
- modified Rankin scale (mRS) scores
研究概览
简要总结
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design. Up to 4,000 patients with presumed acute ischemic stroke (AIS) will be followed for 90 days (or until death, if prior to 90 days). The end of the trial is defined as the date that all participants have completed their Day 90 assessment.
This domain aim is to efficiently, reliably, and simultaneously, determine the comparative effectiveness of intravenous thrombolysis (IVT) using standard-dose intravenous tenecteplase (0.25 mg/kg body weight), vs. low-dose intravenous tenecteplase (0.18 mg/kg body weight) in all patients who present to hospital with acute ischemic stroke and are considered for intravenous thrombolysis. In addition, this domain also seeks to study standard-dose intravenous tenecteplase (0.25 mg/kg body weight), vs. low-dose intravenous tenecteplase (0.18 mg/kg body weight) vs. no TNK upfront with rescue IA TNK if necessary (in those eligible for emergency EVT) and no TNK upfront in those who have taken DOACs during the preceding 24 hours. This domain therefore seeks to generate more robust randomized evidence to guide clinicians in their decisions over the balance of risks and treatment with intravenous thrombolysis with tenecteplase wherever such evidence is currently insufficient.
This domain will currently evaluate four research questions about the use of IVT with tenecteplase:
-
In patients with recent (24 hours) intake of a standard-dose direct oral anticoagulant (DOAC), how should IVT be used? - Use standard-dose (0.25 mg/kg body weight) or low-dose tenecteplase (0.18 mg/kg) or not at all.
-
In patients planned to be treated with endovascular thrombectomy, how should tenecteplase be used? -Treat with IV tenecteplase (standard- or low-dose) or not at all.
-
In any patient receiving IVT, what is the optimal dose of tenecteplase? - use standard-dose (0.25 mg/kg body weight) or low-dose tenecteplase (0.18 mg/kg).
-
To what extent is the treatment effect of standard- vs. low-dose tenecteplase modified by key patient characteristics, such as diabetes, prior antiplatelet therapy, renal failure, or frailty, old age, or having a heavy burden of cerebral small vessel disease on brain imaging?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Age greater than or equal to 18 years
- •Clinical diagnosis of stroke
- •All patients with disabling AIS presenting within 4.5 hours of symptom onset or last known well who may benefit from intravenous thrombolysis (IVT) with tenecteplase.
- •Patients potentially eligible for IVT with conditions described as relative contraindications in national guidelines where physician discretion is recommended are eligible.
- •Patients who received a DOAC, and those planned for EVT are eligible.
- •Consent process completed as per national laws and regulations and the applicable ethics committee requirements.
排除标准
- •Any absolute contraindication for IV thrombolysis per current national guidelines.
- •Examples include those who have active bleeding, recent (less than 7 days) intracranial surgery, head trauma, intracranial or subarachnoid hemorrhage, or have a bleeding diathesis.
- •Minor stroke patients with non-disabling symptoms.
结局指标
主要结局
modified Rankin scale (mRS) scores
时间窗: Day 90
次要结局
- Place of residence(Day 90)
- Ambulatory status at discharge
- Proportion of participants with mRS score of 0-1
- Proportion of participants with mRS score of 0-2
- Health-related quality of life, as measured by the EQ-5D-5L(Day 90)
- Ordinal shift of 7 levels of mRS at 90 days
- Imaging assessments (e.g., infarct and edema volumes)(NIL)
- Proportion of participant achieving revised arterial occlusive lesion [rAOL] score of 2b-3 at first angiographic images (when treated with EVT)
- Proportion of participants achieving first pass reperfusion expanded treatment in cerebral ischemia (eTICI) 2c or higher (when treated with EVT)
- Summative total length of hospital stay in the first 90-days after stroke onset(Day 90)
- Mortality(Day 90)
- Symptomatic intracranial hemorrhage, Large parenchymal hemorrhage (PH-2)(NIL)
- SAEs(Within 4 days)
研究者
Dr P N Sylaja
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum