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

Capital Medical University

Status and phase: Enrolling; Phase 3

Conditions: Stroke

Treatments: Drug: Tenecteplase (0.25mg/kg); Drug: Standard medical treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT06954155

CSA2024YJ007

Details and patient eligibility

About

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 large vessel occlusion between 24-72 hours of symptom onset (including wake-up stroke and unwitnessed stroke).

Full description

Adult acute ischemic stroke patients due to large vessel occlusion (Middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA) with baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 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 ≥1.8, and mismatch volume ≥15mL). 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.

Enrollment: 330 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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);

5. Neuroimaging:

   1. Middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA, middle cerebral artery M1 or M2 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 ≥1.8, and mismatch volume ≥15mL);

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
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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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330 participants in 2 patient groups

Tenecteplase (0.25 mg/kg)

Experimental group

Description:

Tenecteplase (0.25 mg/kg, max 25 mg)

Treatment:

Drug: Tenecteplase (0.25mg/kg)

Standard medical treatment

Active Comparator group

Description:

Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone

Treatment:

Drug: Standard medical treatment