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

NCT05684172 | Completed Phase 2 DMC

• 1 other identifier: ATTENTION IA
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Ischemic Stroke; Intracranial Artery Occlusion; Endovascular Thrombectomy

Keywords

thrombectomy; endovascular treatment; mechanical thrombectomy techniques; tenecteplase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• a modified Rankin Score of 0-3

  90 (± 14 days) after procedure

• Modified Rankin Score

  90 (± 14 days) after procedure

• NIHSS score

  24 hours after procedure

• mortality

  90 (± 14 days) after procedure

• symptomatic intracerebral hemorrhage (ICH)

  within 72 hours after procedure

Study Arms (2)

endovascular thrombectomy

ACTIVE COMPARATOR

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

endovascular thrombectomy+intra-arterial tenecteplase

EXPERIMENTAL

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.

Drug: Tenecteplase; Other: endovascular thrombectomy alone

Interventions

Tenecteplase DRUG

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.

endovascular thrombectomy+intra-arterial tenecteplase

endovascular thrombectomy alone OTHER

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.

endovascular thrombectomy; endovascular thrombectomy+intra-arterial tenecteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)；

Sponsors & Collaborators

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

Study Sites (1)

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

Hefei, Anhui, 239300, China

Location

Related Publications (3)

• Hu W, Nguyen TN, Qureshi M, Chen Z, Tao C, Li R, Yi TY, Feng G, Su J, Cui T, Cao Z, Wang H, Zeng G, Yuan G, Jing X, Luo C, Zhu Y, Qureshi AI, Nogueira RG, Liu X, Abdalkader M. Noncontrast CT vs CT Perfusion Imaging in Patients With Basilar Artery Occlusion: Analysis of the ATTENTION and ATTENTION IA Trials. Neurology. 2025 Aug 12;105(3):e213911. doi: 10.1212/WNL.0000000000213911. Epub 2025 Jul 17.

  PMID: 40674670 DERIVED

• Hu W, Tao C, Wang L, Chen Z, Li D, Chen W, Yi T, Xu L, Yu C, Wang T, Yao X, Cui T, Yuan G, Su J, Chen L, Zhou Z, Ma Z, Wang J, Wang B, Han H, Wang H, Chen J, Zhou P, Cao Z, Ren Y, Cai X, Shi H, Zhang G, Yu L, Yuan X, Li J, Zeng G, Ni C, Li T, Wu Y, Li Y, Li K, Liu Y, Wang Y, Jin Y, Liu H, Wen J, Sun J, Zhu Y, Li R, Zhang C, Liu T, Song J, Wang L, Cheng J, Qureshi AI, Nguyen TN, Saver JL, Nogueira RG, Liu X. Intra-arterial tenecteplase after successful endovascular recanalisation in patients with acute posterior circulation arterial occlusion (ATTENTION-IA): multicentre randomised controlled trial. BMJ. 2025 Jan 14;388:e080489. doi: 10.1136/bmj-2024-080489.

  PMID: 39809509 DERIVED

• Tao C, Li R, Sun J, Zhu Y, Wang L, Zhang C, Liu T, Song J, Qureshi AI, Abdalkader M, Nguyen TN, Saver JL, Nogueira RG, Hu W. Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale. J Neurointerv Surg. 2024 Dec 26;17(e1):e68-e73. doi: 10.1136/jnis-2023-021076.

  PMID: 38124230 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: January 13, 2023
• Study Start: January 24, 2023
• Primary Completion: August 24, 2023
• Study Completion: November 24, 2023
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)