Additive Effects of Intra-arterial Tenecteplase for Successful Thrombectomy Due to Acute Basilar Artery Occlusion (ARTERIAL TNK BAO)：a Prospective, Randomized, Open-label, Blinded Endpoint, Multicenter, Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 520
- 主要终点
- mRS 0-3
研究概览
简要总结
Recent studies revealed the safety and effectiveness of EVT in patients with acute occlusion at basilar artery, showing that up to 46% of patients receiving EVT had favorable functional outcome at 3 months (ATTENTION and BAOCHE trials, ESOC). Although the rate of successful recanalization can be as high as 90% , a large number of these patients remains to be functionally independent while recovery. In addition, a number of recent studies indicated the functional outcome of patients with successful recanalization of TICI 2b was not as good as those with TICI 3 grade. Therefore, restoring reperfusion of distal vessels and territorial microcirculation may be pivotal to further improvement of neurological outcomes for AIS patients receiving EVT. Correspondingly, a very recent Spanish multicenter randomized trial showed the effect of further functional improvement of post-EVT intra-arterial alteplase for successful mechanical thrombectomy in anterior circulation More importantly, head-to-head comparison between TNK and tPA showed the former has a significantly higher chance of reperfusion, indicating that TNK may be a potentially better candidate for post-EVT bridging.
Based on the above findings, we hypothesize in the present study that, adjunct intra-arterial tenecteplase after successful thrombectomy could enhance the functional improvement in patients with acute basilar artery occlusion.
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 - 80 yro；
- •Acute symptomatic basilar artery occlusion identified by neuroimaging modalities (CTA/MRA/DSA)；
- •NIHSS ≥ 6 before thrombectomy；
- •Time from symptom onset (or last seen normal) to arterial TNK/placebo is less than 24 hours；
- •pc-ASPECTS ≥ 6 and Pons-midbrain-index ≤ 2
- •Successful recanalization（eTICI 2b-3）at the end of procedure（The maximum will be six passes or six aspirations for the patient）；Patients with an eTICI score 2b/3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.
- •Exclusion of parenchymal hemorrhagic transformation (DynaCT/XpertCT) before intra-arterial agent administration；
- •Pre-morbid mRS ≤ 1；
- •Patient or legal proxy is able to understand and willing to provide written inform and consent.
排除标准
- •Patient received thrombolysis prior to EVT
- •NIHSS score on admission >25
- •Contraindication to IA TNK as per local national guidelines (except time to therapy)
- •Use of stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h
- •Female who is pregnant or lactating or has a positive pregnancy test at time of admission
- •Current participation in another investigation drug or device treatment study (except observational study)
- •Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
- •Known coagulopathy, INR >1.7 or use of novel anticoagulants < 48h from symptom onset
- •Platelets <100,000
- •Renal Failure as defined by a serum creatinine >3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] <
- •Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
- •Any hemorrhage on CT/MRI
- •Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
- •Suspicion of aortic dissection
- •Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
- •History of life threatening allergy (more than rash) to TNK or contrast medium
- •SBP >185 mmHg or DBP >110 mmHg refractory to treatment
- •Serious, advanced, terminal illness with anticipated life expectancy <6 months
- •Pre-existing neurological or psychiatric disease that would confound evaluation
- •Presumed vasculitis or septic embolization
- •Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas)
- •Other conditions at investigators' discretion which are not appropriate for participation.
研究组 & 干预措施
intra-arterial TNK infusion (0.4mg/min) via support/access catheter, over 15 minutes
干预措施: Tenecteplase for Injection (Drug)
intra-arterial TNK infusion (0.25mg/min) via support/access catheter, over 15 minutes
干预措施: Tenecteplase for Injection (Drug)
intra-arterial placebo infusion via support/access catheter, over 15 minutes
干预措施: Saline (Drug)
结局指标
主要结局
mRS 0-3
时间窗: 90 days
The proportion of patients with a modified Rankin Scale 0 to 3 at 90 days
symptomatic ICH
时间窗: 24 hours
The proportion of symptomatic ICH within 24 hours after allocated intervention
次要结局
- mortality(90 days)
- mRS shift(90 days)
- PH1 and PH2 sICH(24 hours)
- mRS 0-1(90 days)
- mRS 0-2(90 days)
- early neurological improvement(48 hours)
研究者
Chuansheng Zhao
Professor
First Hospital of China Medical University