Intra-arterial Tenecteplase During First Thrombectomy Attempt for Acute Stroke (BRETIS-TNK II)

Intra-arterial Tenecteplase During First Thrombectomy Attempt for Acute Stroke (BRETIS-TNK II): a Prospective, Randomized, Adaptive Enrichment, Open-label, Blinded End Point, Multi-center Study

A recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).

The study aimed to determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic
• Intervention / Treatment: Drug: Tenecteplase

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • ShenYang, China, 110840
    • General Hospital of Northern Theater Command

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years;
• Stroke patient with large vessel occlusion (internal carotid artery, M1 or M2 of middle cerebral artery, basilar artery, or intracranial segment of vertebral artery) who meets criteria for endovascular treatment within 24 hours of stroke onset;
• The modified Rankin Scale (mRS) score before onset ≤ 2;
• ASPECTS 6 or greater on CT
• Signed informed consent.

Exclusion Criteria:

• hemorrhagic stroke;
• Tandem occlusion;
• Coagulation disorders, systematic hemorrhagic tendency, thrombocytopenia (<100000/mm3);
• Severe hepatic or renal dysfunction, increase in ALT or AST (more than 2 times of upper limit of normal value), elevated serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis;
• Severe uncontrolled hypertension (systolic blood pressure over 200mmHg or diastolic blood pressure over 110 mmHg);
• Patients with contraindication or allergic to any ingredient of drugs in our study;
• Pregnancy, or plan to get pregnant or during active lactation;
• Suspected septic embolus or infective endocarditis
• The estimated life expectancy is less than 6 months due to other serious diseases;
• Other conditions unsuitable for this clinical study as assessed by researcher.

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
No Intervention: control group
Experimental: TNK group	Drug: Tenecteplase; intra-arterial tenecteplase during endovascular treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of favorable outcome	Favorable outcome is defined as modified Rankin Scale (mRS) score of 0-2	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of excellent outcome	Excellent outcome is defined as modified Rankin Scale (mRS) score of 0-1	Day 90
proportion of successful reperfusion after the first-pass or final pass of endovascular treatment	Successful reperfusion is defined as defined as modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3	immediately after the first-pass or final pass of endovascular treatment
Distribution of modified Rankin Scale (mRS)	mRS scores range from 0 to 6:0, no symptoms, 1 = symptoms without clinically significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability; and 6 = death.	Day 90
Change in cerebral circulation time after intervention		immediately after endovascular treatment
occurrence rate of early neurological improvement	early neurological improvement was defined as a 4 point or greater decrease in NIHSS	24 (-6/+24) hours
change in National Institute of Health stroke scale (NIHSS)	NIHSS scores range 0-42, with higher scores indicating greater stroke severity	24 (-6/+24) hours
occurrence rate of the composite events of nonfatal stroke, nonfatal myocardial infarction, and other cardiovascular events		Day 90
occurrence rate of symptomatic intracranial hemorrhage	symptomatic intracranial hemorrhage is defined as an increase in the NIHSS score of ≥4 points as a result of the intracranial hemorrhage.	24 (-6/+24) hours
occurrence rate of parenchymal hemorrhage	parenchymal hemorrhage was defined as confluent bleeding occupying and causing mass effect	24 (-6/+24) hours
percentage of severe adverse events		24 (-6/+24) hours
cerebral edema	cerebral edema was measured as the amount of midline shift of the brain on neuroimaging	24 (-6/+24) hours
death due to all causes		Day 7 or during hospitalization
occurrence rate of the distal emboli after first pass	The emboli means occlusion of the distal artery determined by DSA.	immediately after first pass
occurrence rate of extracranial hemorrhage	extracranial hemorrhage means other bleeding events except intracranial hemorrhage	24 (-6/+24) hours

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region
• Collaborators: Cerebrovascular Disease Collaboration & Innovation Alliance of Liaoning

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Actual): March 20, 2025
• Study Completion (Actual): March 20, 2025

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 10, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Tenecteplase
• Other Study ID Numbers: Y (2022) 168

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No