Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-BEYOND (TRACE-BEYOND)

Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-BEYOND--A Multicenter, Prospective, Randomized, Open Label, Blinded-endpoint (PROBE) Controlled Trial of Tenecteplase Versus Standard Medical Treatment for Acute Ischemic Stroke Due to Intracranial Vessel Occlusion With Perfusion Mismatch 24 to 72 Hours of Symptom Onset

The benefit-risk profile of thrombolysis for acute ischemic strokes beyond 24 hours has never been investigated. We initiated a multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled trial to assess the safety and efficacy of tenecteplase (0.25mg/kg, max 25mg) versus standard medical treatment in acute ischemic stroke due to intracranial vessel occlusion between 24-72 hours of symptom onset (including wake-up stroke and unwitnessed stroke).

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Drug: Tenecteplase (0.25mg/kg); Drug: Standard medical treatment

Detailed Description

Adult acute ischemic stroke patients due to middle cerebral artery M1-M4 occlusion, ACA, PCA or basilar artery occlusion confirmed by CTA/MRA with baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 or a score of 4 or 5 with a disabling deficit (e.g., hemianopia, aphasia, and loss of hand function) will be enrolled in this trial. We use perfusion imaging to select subjects and the enrolled patients have target mismatch profile on CTP or MRI+PWI (ischemic core volume <70mL, mismatch ratio >1.2, and mismatch volume >10 mL). We will randomly assign patients who have salvageable brain tissue as identified on perfusion imaging to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 24 to 72 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome is the proportion of patients with an mRS score ≤ 1 at 90 days.

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yongjun Wang; Phone Number: 86-10-59978350; Email: yongjunwang@ncrcnd.org.cn

Study Locations

• China
  • Beijing, China, 100070
    • Recruiting
    • Beijing Tiantan Hospital
    • Contact: Yongjun Wang; Phone Number: 86-10-59978350; Email: yongjunwang@ncrcnd.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1)Age ≥ 18 years old;
• 2)Acute ischemic stroke symptom onset between 24 to 72 hours prior to enrollment; including wake-up stroke and unwitnessed stroke, onset time refers to 'last-seen normal time';
• 3)Pre-stroke modified Rankin scale (mRS) score ≤1;
• 4)Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (both inclusive) or a score of 4 or 5 with a disabling deficit (e.g., hemianopia, aphasia, and loss of hand function);

• 5)Neuroimaging:

  1. Middle cerebral artery M1-M4 occlusion, ACA, PCA or basilar artery occlusion confirmed by CTA/MRA, being responsible for signs and symptoms of acute ischemic stroke;
  2. target mismatch profile on CTP or MRI+PWI (ischemic core volume <70mL, mismatch ratio >1.2, and mismatch volume >10mL);
• 6)Written informed consent from patients or their legally authorized representatives.

Exclusion Criteria:

• 1)Present as a significant low-density lesion on CT
• 2)Allergy to tenecteplase
• 3)Rapidly improving symptoms at the discretion of the investigator
• 4)NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or other neurological/mental illness such that the patient is not able to cooperate or unwilling to cooperate
• 5)Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), despite blood pressure-lowering treatment
• 6)Blood glucose <2.8 or >22.2 mmol/L (point of care glucose testing is acceptable)
• 7)Active internal bleeding or at high risk of bleeding, e.g., major surgery, trauma or gastrointestinal or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days
• 8)Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR >1.7 or prothrombin time >15 seconds; use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours unless reversal of effect can be achieved with a reversal agent; any full dose heparin/heparinoid during the last 24 hours or with an aPTT greater than the upper limit of normal
• 9)Known defect of platelet function or platelet count below 100,000/mm3 (NB patients taking antiplatelet medication can be included)
• 10)Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation, or giant aneurysm
• 11)Any terminal illness such that the patient would not be expected to survive more than 1 year
• 12)Unable to perform CTP or PWI
• 13)Hypodensity in >1/3 MCA territory on non-contrast CT for MCA occlusion, and pc-ASPECTS <6 for BAO
• 14)Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI
• 15)Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion)
• 16)Pregnant women, nursing mothers, or reluctance to use effective contraceptive measures during the period of trial
• 17)Unlikely to adhere to the trial protocol or follow-up
• 18)Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study
• 19)Participation in other interventional clinical trials within the previous 3 months

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
Experimental: Tenecteplase (0.25 mg/kg); Tenecteplase (0.25 mg/kg, max 25 mg)	Drug: Tenecteplase (0.25mg/kg); Each vial of tenecteplase is reconstituted with 3 ml sterile water for injection and adjusted to a concentration of 5.33 mg/ml. Calculate the total amount of drug according to the subject's actual body weight and measure the required drug volume. The maximum dose should not exceed 25mg. Tenecteplase should be given as a single, intravenous bolus (within 5-10 seconds).
Active Comparator: Standard medical treatment; Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone, etc.	Drug: Standard medical treatment; Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone after randomization at the discretion of site researchers according to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS score ≤ 1 at 90 days	The proportion of patients with an mRS score ≤ 1 at 90 days	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 90 days	All-cause mortality at 90 days	90 days
mRS score	Ordinal distribution of mRS at 90 days (shift analysis)	90 days
mRS score ≤ 2 at 90 days	The proportion of patients with an mRS score of 0-2	90 days
early neurological improvement at 24h after randomization	The rate of early neurological improvement at 24h after randomization (defined as a NIHSS score ≤1 or ≥4 points compared with baseline)	24 hours
complete recanalization at 24h after randomization	The rate of complete recanalization at 24h after randomization (defined as an AOL score of 3)	24 hours
Symptomatic intracranial hemorrhage within 36 hours	Symptomatic intracranial hemorrhage within 36 hours (defined by the ECASS III criteria)	36 hours
Systemic bleeding at 90 days	Systemic bleeding at 90 days (defined by the GUSTO criteria: moderate and severe bleeding)	90 days
improvement on reperfusion at 24h after randomization (anterior circulation)	The rate of improvement on reperfusion at 24h after randomization (improved by 90% on Tmax > 6s) for stroke with anterior circulation occlusions	24 hours

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: April 24, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ischemic stroke; tenecteplase; beyond 24 hours
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Amino Acids, Peptides, and Proteins; Proteins; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: CSA2024YJ007

Drug and device information, study documents

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