Intra-arterial TNK Following Endovascular Thrombectomy in Patients With Large Vessel Occlusion of Posterior Circulation

Acute Ischemic Stroke Clinical Trial

Official title:

Trial of Intra-arterial Tenecteplase Following Successful Endovascular Thrombectomy on Safety and Efficacy in Patients With Large Vessel Occlusion of Posterior Circulation - a Multicenter Randomized Clinical Trial (ATTENTION IA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05684172
• Other study ID #: ATTENTION IA
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 24, 2023
• Est. completion date: November 24, 2023

Study information

• Verified date: April 2024
• Source: The First Affiliated Hospital of University of Science and Technology of China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Rationale: Recently, one prospective multicenter RCT reported a potential beneficial effect of intra-arterial alteplase following successful endovascular thrombectomy (EVT) in patients with an acute intracranial large vessel occlusion. In 2018, another prospective multicenter RCT supported the superiority of tenecteplase over alteplase in ischemic stroke patients with large vessel occlusion.

Objective: To assess the effect of EVT in addition to intra-arterial tenecteplase compared to EVT alone, in patients with large vessel occlusion of posterior circulation, on functional and safety outcomes.

Study design: This is a parallel group, randomized clinical trial of EVT with IA-TNK versus EVT. The trial has observer blind assessment of the primary outcome and of neuro-imaging at baseline and follow-up.

Study population: Patients with acute intracranial large vessel occlusion of posterior circulation and an eTICI 2b-3 after EVT.

Main study parameters/outcomes: The primary effect parameter will be excellent functional status at day 90 defined as a modified Rankin Score (mRS) of 0-1. The estimate will be adjusted for the known prognostic variables age, pre-stroke mRS, time from onset to randomization, stroke severity (NIHSS) and collaterals and adjusted and unadjusted estimates with corresponding 95% confidence intervals will be reported.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: November 24, 2023
• Est. primary completion date: August 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Acute ischemic stroke patients with symptomatic intracranial large vessel occlusion (LVO) in the intracranial vertebral artery, basilar artery, or the P1 segment of the posterior cerebral artery.

• Treated with endovascular thrombectomy (EVT) resulting in an eTICI score 2b50/3 at end of the procedure.

• Age of 18 years or older;

• National Institutes of Health Stroke Scale (NIHSS) score on admission=6;

• Posterior Circulation ASPECTS = 6 on CT/CTA-Source Images/MRI-DWI.

• Time from estimated time of basilar artery occlusion to randomization<24 hours;

• Written informed consent.

Exclusion criteria

• Pre-existing dependency with mRS >1;

• Contraindication to Intravenous Thrombolysis (except time to therapy);

• Complete clinical recovery in the angiography suite by end of EVT procedure;

• Pregnancy; if a woman is of childbearing potential a urine or serum beta HCG test is positive;

• Severe contrast allergy or absolute contraindication to iodinated contrast;

• Participation in other investigational drug or device clinical trials;

• Systolic pressure >185 mmHg or diastolic pressure >110 mmHg, and cannot be controlled by antihypertensive drugs;

• Known genetic or acquired bleeding diathesis, lack of anticoagulant factors, or oral anticoagulant drugs and INR > 1.7, or treated with direct oral anticoagulant agents in the prior 48 hours;

• platelets <100 000/mm3, aPTT >40 s, or PT >15 s; Blood glucose < 2.7 or >22.2 mmol/L;

• Severe renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 µmol/l) or glomerular Filtration Rate [GFR] < 30, or patient requires hemodialysis or peritoneal dialysis;

• Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal;

• Suspicion of aortic dissection;

• Presumed vasculitis or septic embolization;

• Life expectancy < 1 year;

• Patients that cannot complete 90-day follow-up (e.g. no fixed residence, overseas patients, etc.);

• CT/MR shows intracranial hemorrhage;

• Ischemic stroke within 3 months;

• Severe head trauma within 3 months;

• Major surgery or severe trauma within the last 2 weeks.

• History of prior intracranial hemorrhage.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Endovascular Thrombectomy
• Intracranial Artery Occlusion
• Ischemic Stroke

Intervention

Drug:
• Tenecteplase
If patients are randomized and assigned to receive intra-arterial tenecteplase thrombolysis, tenecteplase will be injected according to protocol, proceeding to inject TNK through a distal access catheter or microcatheter located proximal to the residual thrombus (if still present) and distally to the origin of the pontine arteries.

Other:
• endovascular thrombectomy alone
Patients will receive randomization if the eTICI score on cerebral angiography is 2b-3 and will stop the procedure if they have been assigned to the control group.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine	Hefei	Anhui

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of University of Science and Technology of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	a modified Rankin Score of 0-1	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	a modified Rankin Score of 0-3	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	Modified Rankin Score	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	NIHSS score	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
Secondary	mortality	(Number of subjects who died at 90-day follow-up/total number of subjects who participated in 90-day follow-up) x100%	90 (± 14 days) after procedure
Secondary	symptomatic intracerebral hemorrhage (ICH)	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