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

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)

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke; Intracranial Artery Occlusion; Endovascular Thrombectomy
• Intervention / Treatment: Other: endovascular thrombectomy alone; Drug: Tenecteplase

Detailed Description

This trial is a clinical evaluation to assess the safety and effectiveness of intra-arterial tenecteplase in acute ischemic stroke patients with an acute intracranial large vessel occlusion and successful reperfusion (eTICI 2b50-3) after EVT.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 239300
      • The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

Participation Criteria

Eligibility Criteria

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

Description

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.

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
Active Comparator: endovascular thrombectomy; For patients randomized to the control group, EVT has to be completed within 24 hours of stroke onset. The choice of EVT strategy will be made by the treating neurointerventionalist. All mechanical thrombectomy devices for EVT, which are approved by CFDA for this purpose, are allowed in the trial.	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.
Experimental: endovascular thrombectomy+intra-arterial tenecteplase; For patients randomized to the endovascular treatment arm, 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 lenticulostriates branches. The administration of TNK will be infused for 15 seconds.	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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2023
• Primary Completion (Actual): August 24, 2023
• Study Completion (Actual): November 24, 2023

Study Registration Dates

• First Submitted: January 5, 2023
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: endovascular treatment; tenecteplase; thrombectomy; mechanical thrombectomy techniques
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: ATTENTION IA

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