Additive Effects of Intra-arterial Tenecteplase for Successful Thrombectomy Due to Acute Basilar Artery Occlusion

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Basilar Artery Occlusion; Thrombectomy; Tenecteplase
• Intervention / Treatment: Drug: Tenecteplase for Injection; Drug: Saline

• Study Type: Interventional
• Enrollment (Anticipated): 520
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 - 80 yro；
2. Acute symptomatic basilar artery occlusion identified by neuroimaging modalities (CTA/MRA/DSA)；
3. NIHSS ≥ 6 before thrombectomy；
4. Time from symptom onset (or last seen normal) to arterial TNK/placebo is less than 24 hours；
5. pc-ASPECTS ≥ 6 and Pons-midbrain-index ≤ 2
6. 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.
7. Exclusion of parenchymal hemorrhagic transformation (DynaCT/XpertCT) before intra-arterial agent administration；
8. Pre-morbid mRS ≤ 1；
9. Patient or legal proxy is able to understand and willing to provide written inform and consent.

Exclusion Criteria:

1. Patient received thrombolysis prior to EVT
2. NIHSS score on admission >25
3. Contraindication to IA TNK as per local national guidelines (except time to therapy)
4. Use of stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h
5. Female who is pregnant or lactating or has a positive pregnancy test at time of admission
6. Current participation in another investigation drug or device treatment study (except observational study)
7. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
8. Known coagulopathy, INR >1.7 or use of novel anticoagulants < 48h from symptom onset
9. Platelets <100,000
10. Renal Failure as defined by a serum creatinine >3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] <30.
11. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
12. Any hemorrhage on CT/MRI
13. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
14. Suspicion of aortic dissection
15. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
16. History of life threatening allergy (more than rash) to TNK or contrast medium
17. SBP >185 mmHg or DBP >110 mmHg refractory to treatment
18. Serious, advanced, terminal illness with anticipated life expectancy <6 months
19. Pre-existing neurological or psychiatric disease that would confound evaluation
20. Presumed vasculitis or septic embolization
21. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas)
22. Other conditions at investigators' discretion which are not appropriate for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intra-arterial TNK infusion (0.4mg/min) via support/access catheter, over 15 minutes	Drug: Tenecteplase for Injection; intra-arterial TNK infusing after successful thrombectomy for patient with acute basilar artery occlusion via support/access catheter
Experimental: intra-arterial TNK infusion (0.25mg/min) via support/access catheter, over 15 minutes	Drug: Tenecteplase for Injection; intra-arterial TNK infusing after successful thrombectomy for patient with acute basilar artery occlusion via support/access catheter
Placebo Comparator: intra-arterial placebo infusion via support/access catheter, over 15 minutes	Drug: Saline; intra-arterial saline infusing after successful thrombectomy for patient with acute basilar artery occlusion via support/access catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS 0-3	The proportion of patients with a modified Rankin Scale 0 to 3 at 90 days	90 days
symptomatic ICH	The proportion of symptomatic ICH within 24 hours after allocated intervention	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS 0-1	The proportion of patients with a mRS 0 to 1 at 90 days	90 days
mRS 0-2	The proportion of patients with a mRS 0 to 2 at 90 days	90 days
mRS shift	The proportion of patients with a mRS shift at 90 days	90 days
early neurological improvement	The proportion of patients with early neurological improvement (NIHSS reduction > 4) at 48 hours	48 hours
PH1 and PH2 sICH	The proportion of subtypes (PH1 and PH2) of sICH within 24 hours after allocated intervention	24 hours
mortality	The proportion of mortality at 90 days	90 days

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: ARTERIAL-TNK-BAO-202201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No