Clinical trial NCT05701956: Intravenous Tenecteplase Plus EVT Versus EVT Alone on 4.5 to 24 Hours After Basilar Artery Occlusion
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Basilar Artery Occlusion
Acute Cerebrovascular Accident
Stroke Due to Basilar Artery Occlusion
Keywords: Thrombectomy
Tenecteplase
Mechanical Thrombectomy
Lead sponsor: The First Affiliated Hospital of University of Science and Technology of China
Sponsor class: OTHER
First posted: 2023-01-27
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Proportion of patients with modified Rankin Score 0-2 at day 90 (±14 days)
timeFrame: 90 (± 14 days) after procedure
Secondary outcomes:
measure: Proportion of patients with modified Rankin Score 0-3 at day 90 (±14 days)
timeFrame: 90 (± 14 days) after procedure
measure: Ordinal Shift analysis of modified Rankin Score at day 90 (±14 days)
timeFrame: 90 (± 14 days) after procedure
measure: Score on the NIHSS at 24 hours
timeFrame: 24 hours after procedure
measure: Score on the NIHSS at 5-7 days or discharge
timeFrame: 5-7 days or discharge after procedure
measure: Proportion of patients with modified Rankin Score 0-1 at day 90 (±14 days)
timeFrame: 90 (± 14 days) after procedure
measure: Proportion of patients with modified Rankin Score 0-4 at day 90 (±14 days)
timeFrame: 90 (± 14 days) after procedure
measure: Score on the EuroQoL 5-dimensions 5-level (EQ5D-5L) at 90 days (±14 days)
timeFrame: 90 (± 14 days) after procedure
measure: level of activities of daily living (Barthel index, BI) at 90 days (±14 days)
timeFrame: 90 (± 14 days) after procedure
measure: Successful reperfusion (Extended thrombolysis in cerebral infarction [eTICI] score 2b50-3) on digital substraction angiography (DSA) prior to thrombectomy
timeFrame: within 5 minutes at angiography
measure: Successful reperfusion on final angiography of thrombectomy
timeFrame: Within 5 minutes at final angiography of thrombectomy
measure: Successful recanalization on CT or MR angiography within 72 hours
timeFrame: Within 72 hours after procedure
measure: Infarct volume (Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score, PC-ASPECTS) evaluated on CT or MRI within 72 hours
timeFrame: Within 72 hours after procedure
Other outcomes:
measure: Overall mortality at 7 (± 2 days) and 90 (± 14 days)
timeFrame: 7 (± 2 days) and 90 (± 14 days) after procedure
measure: Symptomatic intracerebral hemorrhage (sICH) within 72 hours
timeFrame: Within 72 hours after procedure
measure: Any intracerebral hemorrhage within 72 hours
timeFrame: Within 72 hours after procedure
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China
state: Anhui
Study officials:
affiliation: The First Affiliated Hospital of University of Science and Technology of China
name: Wei Hu, MD
role: STUDY_CHAIR
References: