Improving Neurological Outcome for Acute Basilar Artery Occlusion With Sufficient Recanalization After Thrombectomy by Intraarterial Tenecteplase (INSIST-IT)

Improving Neurological Outcome for Acute Basilar Artery Occlusion With Sufficient Recanalization After Thrombectomy by Intraarterial Tenecteplase (INSIST-IT): a Prospective, Randomized, Open-label, Blinded-end Point, Multicenter Trial

The potential benefit of intraarterial tenecteplase in acute basilar artery occlusion (BAO) patients with successful reperfusion following endovascular treatment (EVT) has not been studied. The current study aimed to explore the efficacy and safety of intraarterial tenecteplase in acute BAO patients with successful reperfusion after EVT.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • ShenYang, China, 110840
    • Recruiting
    • General Hospital of Northern Theater Command
    • Contact: Zi-Ai Zhao; Phone Number: +862428897499; Email: zhaoziai@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18
• Patients with basilar artery occlusion who received endovascular treatment within 24 hours of estimated time of stroke onset as per BASICS trial definition;
• National Institute of Health Stroke Scale (NIHSS) ≥ 6 before endovascular treatment;
• Successful recanalization (mTICI 2b-3) after endovascular treatment;
• PC-ASPECTS ≥ 6 on CT;
• Absence of parenchymal hematoma on CT images done in the angio suite immediately after the procedure;
• Modified Rankin Scale score before stroke onset ≤ 3;
• Signed informed consent by patient or their legally authorized representative.

Exclusion Criteria:

• baseline PC ASPECTS < 5 on CT;
• More than six retrieval attempts in the same vessel;
• Hemorrhagic stroke: cerebral hemorrhage, subarachnoid hemorrhage;
• Coagulation disorders, systemic hemorrhagic diathesis, thrombocytopenia (<100000/mm3), or INR > 1.7;
• Severe hepatic or renal dysfunction, increase in ALT or AST (more than 2 times of upper limit of normal value), increase in serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis;
• After recanalization, severe and sustained (i.e., > 5 minutes) uncontrolled hypertension (systolic blood pressure over 180mmHg or diastolic blood pressure over 105 mmHg) refractory to antihypertensive medication;
• Patients with contraindication or allergic to any ingredient of drugs in our study
• Pregnancy, plan to get pregnant or during lactation
• The estimated life expectancy is less than 6 months due to other serious diseases;
• Other conditions unsuitable for this clinical study 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of favorable functional outcome	favorable functional outcome is defined as a modified Rankin Scale (mRS) score of 0 to 3	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients with an improved modified thrombolysis in cerebral infarction score		immediately after intraarterial TNK administration or at the end of endovascular treatment
the proportion of patients with modified Rankin Score (mRS) 0 to 1	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
the proportion of patients with modified Rankin Score (mRS) 0 to 2	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
ordinal distribution of modified Rankin Score (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 National Institute of Health stroke scale (NIHSS)	NIHSS scores range from 0 to 42, with higher scores indicating more severe neurological deficit	24 (-6/+24) hours
proportion of early neurological improvement	early neurological improvement is defined as a NIHSS decrease ≥4	24 (-6/+24) hours
change in the cerebral circulation time		immediately after tenecteplase
the occurrence rate of composite events of recurrent stroke, cardiovascular or cerebrovascular events		Day 90
proportion of sympomatic intracranial hemorrhage	sympomatic intracranial hemorrhage is defined as a NIHSS increase ≥4 caused by intracranial hemorrhage	24 (-6/+24) hours
proportion of intraparenchymal hemorrhage	intraparenchymal hemorrhage was defined as confluent bleeding occupying and causing mass effect	24 (-6/+24) hours
the percentage of severe adverse events		24 (-6/+24) hours
cerebral edema	cerebral edema was measure by the mount of midline shift of the brain on neuroimaging	24 (-6/+24) hours
all-cause mortality		10 days
change in modified Rankin Score (mRS) compared with premorbid 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
the number of tenecteplase infusions interrupted due to suspected active bleeding		during endovascular treatment (up to 2 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 (Anticipated): March 15, 2025
• Study Completion (Anticipated): March 15, 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 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• 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: Y (2022) 185

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