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

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Primary Purpose

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Tenecteplase

endovascular thrombectomy alone

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring thrombectomy, endovascular treatment, mechanical thrombectomy techniques, tenecteplase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

endovascular thrombectomy

endovascular thrombectomy+intra-arterial tenecteplase

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)

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)

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.

mortality

(Number of subjects who died at 90-day follow-up/total number of subjects who participated in 90-day follow-up) x100%

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.

Full Information

NCT ID

NCT05684172

First Posted

January 5, 2023

Last Updated

July 16, 2023

Sponsor

The First Affiliated Hospital of University of Science and Technology of China

1. Study Identification

Unique Protocol Identification Number

NCT05684172

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 24, 2023 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The First Affiliated Hospital of University of Science and Technology of China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Ischemic Stroke, Intracranial Artery Occlusion, Endovascular Thrombectomy

Keywords

thrombectomy, endovascular treatment, mechanical thrombectomy techniques, tenecteplase

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

208 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

endovascular thrombectomy

Arm Type

Active Comparator

Arm Description

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.

Arm Title

endovascular thrombectomy+intra-arterial tenecteplase

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Tenecteplase

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

endovascular thrombectomy alone

Intervention Description

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.

Primary Outcome Measure Information:

Title

a modified Rankin Score of 0-1

Description

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)

Time Frame

90 (± 14 days) after procedure

Secondary Outcome Measure Information:

Title

a modified Rankin Score of 0-3

Description

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)

Time Frame

90 (± 14 days) after procedure

Title

Modified Rankin Score

Description

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)

Time Frame

90 (± 14 days) after procedure

Title

NIHSS score

Description

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.

Time Frame

24 hours after procedure

Title

mortality

Description

(Number of subjects who died at 90-day follow-up/total number of subjects who participated in 90-day follow-up) x100%

Time Frame

90 (± 14 days) after procedure

Title

symptomatic intracerebral hemorrhage (ICH)

Description

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.

Time Frame

within 72 hours after procedure

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wei Hu, MD, PhD

Phone

+86 055162284313

Email

andinghu@ustc.edu.cn

Facility Information:

Facility Name

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

City

Hefei

State/Province

Anhui

ZIP/Postal Code

239300

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wei Hu, PhD

Phone

8655162284076

12. IPD Sharing Statement

Plan to Share IPD

No

Acute Ischemic Stroke, Intracranial Artery Occlusion, Endovascular Thrombectomy

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial