Tenecteplase for Acute Ischemic Stroke Within 4.5 to 6 Hours of Onset (EXIT-BT2)

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5 to 6 Hours of Onset (EXIT-BT2): a Prospective, Randomized, Open Label, Blinded Endpoint, and Multi-center Study

To date, the benefit of intravenous thrombolysis is confined within 4.5 hours of onset for acute ischemic stroke (AIS) patients without advanced neuroimaging selection. Unpublished pilot EXIT-BT (EXtending the tIme window of Thrombolysis by ButylphThalide up to 6 Hours after onset) suggest the safety, feasibility and potential benefit of intravenous tenecteplase (TNK) in AIS within 4.5 to 6 hours of onset. The current study aims to investigate the efficacy and safety of TNK for AIS within 4.5 to 6 hours of onset.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 1250
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shenyang, China, 110016
    • Recruiting
    • Department of Neurology, General Hospital of Northern Theater Command
    • Contact: Hui-Sheng Chen, Ph.D.; Phone Number: +86 13352452086; Email: chszh@aliyun.com
  • None Selected
    • ShenYang, None Selected, China, 110840
      • Recruiting
      • Hui-Sheng Chen
      • Contact: Yi-Han Wang; Phone Number: +862428897524; Email: wangyihan34732512@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 year
• Acute ischemic stroke confirmed by non-contrast computed tomography;
• The time from last known well to treatment: 4.5 - 6 hours;
• NIHSS ≥ 4 at randomization;
• First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
• Signed informed consent.

Exclusion Criteria:

• Pre-stroke disability (mRS≥2);
• Planned intravenous thrombolysis based on WAKE-UP or EXTEND study criterion;
• Any contraindication to intravenous thrombolysis: Obvious head injury or stroke within 3 months; Subarachnoid or intracranial hemorrhage; History of intracranial hemorrhage; Intracranial tumor, arteriovenous malformation or aneurysm; Intracranial or spinal cord surgery within 3 months; Myocardial infarction within 3 months; Major surgery within 1 month; Gastrointestinal or urinary tract hemorrhage within the previous 30 days; Arterial puncture at a noncompressible site within the previous seven days; Active internal hemorrhage; Coagulation abnormalities: platelet count of <100000/mm3; Aortic arch dissection; Heparin therapy within 24 hours; Infective endocarditis; Oral warfarin is being taken and INR>1.6 or APTT abnormal; Systolic pressure ≥185 mmHg or diastolic pressure ≥110 mmHg; Blood glucose < 50 mg/dl (2.7mmol/L); Neurological deficit after epileptic seizures;
• Pregnancy;
• Allergy to test drugs;
• Comorbidity with other serious diseases;
• Participating in other clinical trials within 3 months;
• Patients not suitable for the study considered 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
Other: Control group; standard stroke care based on national guideline	Drug: Tenecteplase; intravenous tenecteplase (0.25 mg/kg, a single bolus over 5 to 10 seconds, a maximum of 25 mg).
Experimental: Tenecteplase group; intravenous thrombolysis with tenecteplase	Drug: Tenecteplase; intravenous tenecteplase (0.25 mg/kg, a single bolus over 5 to 10 seconds, a maximum of 25 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of modified Rankin Scale (mRS) 0-1	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of modified Rankin Scale (mRS) 0-2	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
ordinal distribution of modified Rankin Scale (mRS)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome.	24 (-6/+12) hours
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome.	10±2 days
occurrence of early neurological improvement (ENI)	ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score	24 (-6/+12) hours
new stroke or other vascular event(s)		90±7 days
all-cause mortality		90±7 days
intracranial hemorrhage	any evidence of bleeding on the head CT scan, classified by the Heidelberg Bleeding Classification	24 (-6/+12) hours
major systemic bleeding event		24 (-6/+12) hours
any bleeding event		24 (-6/+12) hours
symptomatic intracranial hemorrhage (sICH)	sICH is defined as parenchymal hematoma type 1 or 2 (PH1 or PH2), remote intraparenchymal hematoma (RIH), subarachnoid hemorrhage, or intraventricular hemorrhage on head CT/MRI scan causally associated with clinically significant neurological deterioration (NIHSS score ≥4 point increase) in the opinion of the clinical investigator or independent safety monitor.	24 (-6/+12) hours

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): March 15, 2025
• Study Completion (Estimated): March 15, 2025

Study Registration Dates

• First Submitted: August 20, 2023
• First Submitted That Met QC Criteria: August 20, 2023
• First Posted (Actual): August 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: thrombolysis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: Y (2023) 144

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