Tenecteplase treatment for ischemic stroke between 24 and 72 hours after symptom onset

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

This trial will try whether a single dose of tenecteplase helps adults with an ischemic stroke from a blocked brain artery when given 24–72 hours after they were last seen well.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 330 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Locations: 1 site (Beijing)
• Trial ID: NCT06954155 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, open-label trial with blinded outcome adjudication enrolls adults with intracranial vessel occlusion and salvageable brain tissue on perfusion imaging 24–72 hours after last known well. Eligible patients have an NIHSS of 6–25 (or 4–5 with a disabling deficit) and a target mismatch profile on CTP or MRI perfusion. Participants are randomly assigned to a single IV bolus of tenecteplase (0.25 mg/kg, max 25 mg) or standard medical treatment. The primary outcome is the proportion of patients with a modified Rankin Scale score of 0–1 at 90 days.

Who should consider this trial

Good fit: Adults (≥18) with an acute ischemic stroke due to MCA, ACA, PCA or basilar occlusion, last seen well 24–72 hours earlier (including wake-up or unwitnessed strokes), pre-stroke mRS ≤1, NIHSS 6–25 (or 4–5 with disabling deficit), and a target mismatch on perfusion imaging (core <70 mL, mismatch ratio >1.2, mismatch volume >10 mL) are ideal candidates.

Not a fit: Patients with a large established infarct core (>70 mL), no target mismatch on perfusion imaging, contraindications to thrombolysis (including allergy to tenecteplase), rapidly improving symptoms, significant pre-stroke disability, or those who cannot reach the enrolling center within the 24–72 hour window are unlikely to benefit.

Why it matters

Potential benefit: If successful, this could expand the time window for thrombolytic therapy and increase the number of patients who regain independence after ischemic stroke.

How similar studies have performed: Tenecteplase has shown benefit in earlier and some extended time windows, but randomized trials of thrombolysis beyond 24 hours have not previously been done.

Eligibility criteria

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

Where this trial is running

Beijing

• Beijing tiantan hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Yongjun Wang

Conditions Stroke; ischemic stroke; tenecteplase; beyond 24 hours