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
Overview
- Phase
- Phase 2
- Intervention
- Tenecteplase for Injection
- Conditions
- Basilar Artery Occlusion
- Sponsor
- First Hospital of China Medical University
- Enrollment
- 520
- Primary Endpoint
- mRS 0-3
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Chuansheng Zhao
Professor
First Hospital of China Medical University
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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 \[GFR\] \<
Arms & Interventions
intra-arterial TNK infusion (0.4mg/min) via support/access catheter, over 15 minutes
Intervention: Tenecteplase for Injection
intra-arterial TNK infusion (0.25mg/min) via support/access catheter, over 15 minutes
Intervention: Tenecteplase for Injection
intra-arterial placebo infusion via support/access catheter, over 15 minutes
Intervention: Saline
Outcomes
Primary Outcomes
mRS 0-3
Time Frame: 90 days
The proportion of patients with a modified Rankin Scale 0 to 3 at 90 days
symptomatic ICH
Time Frame: 24 hours
The proportion of symptomatic ICH within 24 hours after allocated intervention
Secondary Outcomes
- 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)