Intravenous Tenecteplase Plus EVT Versus EVT Alone on 4.5 to 24 Hours After Basilar Artery Occlusion

Intravenous Tenecteplase Plus Endovascular Thrombectomy Versus Endovascular Thrombectomy Alone on 4.5 to 24 Hours After Stroke Due to Basilar Artery Occlusion -a Multicenter, Randomized Controlled, Clinical Trial

To assess the effect of intravenous tenecteplase plus endovascular thrombectomy (EVT) compared to EVT alone on 4.5 to 24 hours after stroke due to basilar artery occlusion.

Study Overview

• Status: Recruiting
• Conditions: Basilar Artery Occlusion; Acute Cerebrovascular Accident; Stroke Due to Basilar Artery Occlusion
• Intervention / Treatment: Drug: Tenecteplase; Procedure: Endovascular thrombectomy

Detailed Description

Background and Rationale: Recently, two prospective multicenter RCT (ATTENTION and BAOCHE trials) have shown a significantly beneficial effect of EVT in patients with an acute symptomatic basilar artery occlusion. The EXTEND-IA TNK trial demonstrated that intravenous thrombolysis with tenecteplase is superior to alteplase before EVT for anterior circulation large vessel occlusion strokes. However, it is unclear whether intravenous tenecteplase bridging with EVT is superior to EVT alone in the extended window patients with basilar artery occlusion. Therefore, additional studies are needed to explore the potential benefit of intravenous tenecteplase in these patients.

Study design: Multicenter, prospective, controlled clinical trial with open-label treatment and blind outcome assessment (PROBE) of intravenous tenecteplase plus EVT versus EVT alone. The trial has observer blinded assessment of the primary outcome and neuroimaging at baseline and follow up.

• Study Type: Interventional
• Enrollment (Estimated): 332
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wei Hu, MD; Phone Number: +8615155510611; Email: andinghu@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China
      • Contact: Wei Hu, MD; Phone Number: +8615155510611; Email: andinghu@ustc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients presenting with posterior circulation ischemic stroke symptoms due to basilar artery occlusion or vertebral artery occlusions that prevent antegrade flow into the basilar artery;
2. Time from stroke onset to randomization within 4.5-24 hours of estimated time of basilar artery occlusion;
3. Patient's age≥18 years;
4. Presence of basilar artery or vertebral artery occlusion, confirmed by CT Angiography (CTA), MR Angiography (MRA) or Digital Subtraction Angiography (DSA). In cases of vertebral artery occlusion, the occlusion must completely prevent antegrade flow into the basilar artery;
5. Patients presenting with acute ischemic stroke eligible using standard criteria (except for time window) to receive both endovascular thrombectomy and intravenous thrombolysis;
6. Baseline National Institutes of Health Stroke Scale (NIHSS) score≥ 10 at the time of neuroimaging;
7. The patient or patient's legal representative signs the informed consent form.

Exclusion Criteria:

1. CT or MR evidence of intracerebral hemorrhage (the presence of < 10 microbleeds is allowed);
2. Pre-stroke modified Rankin scale (mRS) score of ≥ 2;
3. Posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) on CT/ CTA-Source Images<6; PC-ASPECTS on magnetic resonance imaging-diffusion weighted imaging (MRI-DWI) <5;
4. Pregnant or lactating women;
5. Allergy to contrast agent or nitinol alloy;
6. Life expectancy<1 year;
7. CTA/MRA/DSA show vascular tortuosity, vascular variation or artery dissection, which would make it difficult to perform endovascular treatment;
8. Participating in other clinical trials;
9. Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, which cannot be controlled by antihypertensive drugs;
10. Genetic or acquired hemorrhagic diathesis, lack of anticoagulant factor; or oral anticoagulant with international normalized ratio (INR) > 1.7, or novel oral anticoagulant within prior 48 hours;
11. Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L), platelet< 100*109/L;
12. Renal insufficiency defined as serum creatinine >2.0 mg/dl (or 176.8 μ mol/l) or a glomerular filtration rate <30 mL/min or the need for hemodialysis or peritoneal dialysis;
13. Patients who cannot complete 90-day follow-up (such as patients without fixed residence, overseas patients, etc);
14. The patient has acute ischemic cerebral infarction within 3 months from randomization;
15. The patient had a history of or clinical suspicion for cerebral vasculitis or infectious endocarditis;
16. The patient has nervous system disease or mental disorder before stroke onset, which may affect the assessment of their condition;
17. CT or MR examination showed large cerebellar infarction with obvious space occupying effect and compression of the fourth ventricle;
18. Patients with extensive bilateral thalamic or extensive bilateral brainstem infarction on CT or MR examination;
19. CTA/MRA/DSA show both anterior and posterior circulation large vessel occlusion;
20. Patients with intracranial tumors (except small meningiomas);
21. Patients who received intravenous thrombolytics treatment before the randomization;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous tenecteplase+endovascular thrombectomy; Patients will receive intravenous tenecteplase (0.25mg/kg, max 25mg) plus endovascular thrombectomy.	Drug: Tenecteplase; Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds) before endovascular thrombectomy; Other Names: TNK; TNKase; TNK-tPA; rhTNK-tPA; Procedure: Endovascular thrombectomy; The choice of endovascular thrombectomy strategy will be made by the treating neurointerventionist. All thrombectomy devices for endovascular treatment, which are approved by CFDA for this purpose, are allowed in the trial.; Other Names: thrombectomy
Active Comparator: Endovascular thrombectomy alone; Patients will receive endovascular thrombectomy alone.	Procedure: Endovascular thrombectomy; The choice of endovascular thrombectomy strategy will be made by the treating neurointerventionist. All thrombectomy devices for endovascular treatment, which are approved by CFDA for this purpose, are allowed in the trial.; Other Names: thrombectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with modified Rankin Score 0-2 at day 90 (±14 days)	modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90 (± 14 days) after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with modified Rankin Score 0-3 at day 90 (±14 days)	modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90 (± 14 days) after procedure
Ordinal Shift analysis of modified Rankin Score at day 90 (±14 days)	modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90 (± 14 days) after procedure
Score on the NIHSS at 24 hours	The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.	24 hours after procedure
Score on the NIHSS at 5-7 days or discharge	The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.	5-7 days or discharge after procedure
Score on the EuroQoL 5-dimensions 5-level (EQ5D-5L) at 90 days (±14 days)	Health-related quality of life, assessed with EQ-5D-5L	90 (± 14 days) after procedure
level of activities of daily living (Barthel index, BI) at 90 days (±14 days)	Level of activities of daily living	90 (± 14 days) after procedure
Successful reperfusion (Extended thrombolysis in cerebral infarction [eTICI] score 2b50-3) on digital substraction angiography (DSA) prior to thrombectomy	Evaluate effect of intravenous thrombolysis on reperfusion	within 5 minutes at angiography
Successful reperfusion on final angiography of thrombectomy	Evaluate effect of thrombectomy on reperfusion	Within 5 minutes at final angiography of thrombectomy
Successful recanalization on CT or MR angiography within 72 hours	Evaluate vascular patency after treatment	Within 72 hours after procedure
Infarct volume (Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score, PC-ASPECTS) evaluated on CT or MRI within 72 hours	PC-ASPECTS=10 indicates a normal scan, PC-ASPECTS=0 indicates early ischemic changes or hypoattenuation in all above territories. 1 or 2 points each are subtracted for early ischemic changes or hypoattenuation in: left or right thalamus, cerebellum or posterior cerebral artery territory, respectively (1 point); any part of midbrain or pons (2 points)	Within 72 hours after procedure
Proportion of patients with modified Rankin Score 0-1 at day 90 (±14 days)	modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90 (± 14 days) after procedure
Proportion of patients with modified Rankin Score 0-4 at day 90 (±14 days)	modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)	90 (± 14 days) after procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall mortality at 7 (± 2 days) and 90 (± 14 days)	evaluate death rate	7 (± 2 days) and 90 (± 14 days) after procedure
Symptomatic intracerebral hemorrhage (sICH) within 72 hours	SICH means any hemorrhage with neurological deterioration, as indicated by an NIHSS score that was higher by ≥4 points than the value at baseline or the lowest value in the first 72 hours or any hemorrhage leading to death	Within 72 hours after procedure
Any intracerebral hemorrhage within 72 hours	Evaluate intracerebral hemorrhage	Within 72 hours after procedure

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of University of Science and Technology of China
• Investigators: Study Chair: Wei Hu, MD, The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 16, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Thrombectomy; Mechanical Thrombectomy; Tenecteplase
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Arterial Occlusive Diseases; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: ATTENTION-IV LATE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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