Tenecteplase for adults with medium-vessel ischemic stroke treated 4.5–24 hours after last seen well

Advancing Reperfusion Therapy for Ischemic Stroke (ARTS): Tenecteplase in Medium Vessel Occlusion (MeVO) for Acute Ischemic Stroke

This trial will test whether a single dose of tenecteplase helps adults with medium-vessel ischemic stroke when given 4.5 to 24 hours after they were last seen well.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 596 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Drugs / interventions: idarucizumab
• Locations: 7 sites (Beijing, Beijing Municipality and 6 other locations)
• Trial ID: NCT07047014 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, open-label, blinded-endpoint (PROBE) trial comparing tenecteplase (0.25 mg/kg, max 25 mg) to standard medical care for acute ischemic stroke caused by medium vessel occlusions treated 4.5–24 hours after last known well. Eligible adults must have a primary medium-vessel occlusion confirmed by CTA/MRA and either a target perfusion mismatch on CTP or MRI/PWI (core <70 mL, mismatch ratio >1.2, mismatch volume >10 mL) or an ASPECTS/PC-ASPECTS ≥8 if perfusion is unavailable. Patients are randomized to receive tenecteplase or standard care and followed for clinical outcomes, with the primary endpoint being the proportion with a modified Rankin Scale score ≤1 at 90 days. The trial is led by Beijing Tiantan Hospital with multiple Chinese hospital sites participating.

Who should consider this trial

Good fit: Adults (≥18) with acute ischemic stroke from a confirmed medium vessel occlusion within 4.5–24 hours of last seen well, NIHSS ≥6 (or 3–5 with disabling symptoms), pre-stroke mRS ≤1, and imaging showing target perfusion mismatch or ASPECTS/PC-ASPECTS ≥8.

Not a fit: Patients with a large ischemic core (≥70 mL), no target mismatch on perfusion imaging, pre-existing significant disability (mRS >1), intracranial hemorrhage, or those outside the 4.5–24 hour window are unlikely to benefit from the intervention in this protocol.

Why it matters

Potential benefit: If successful, this approach could increase the chance of an excellent recovery (mRS ≤1) for patients with medium-vessel occlusions treated in the extended 4.5–24 hour window.

How similar studies have performed: Previous trials have shown tenecteplase can be beneficial or noninferior to alteplase in early windows and in some large-vessel occlusions, but its use specifically for medium-vessel occlusions in the 4.5–24 hour window is largely untested.

Eligibility criteria

Inclusion Criteria:

* (1)Age≥18 years old;
* (2)Acute ischemic stroke symptom onset within 4.5 - 24 hours; including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
* (3)Primary medium vessel occlusions confirmed by CTA/MRA, including distal M2/M3 segments of the middle cerebral artery (MCA), A1/A2/A3 segments of the anterior cerebral artery (ACA), and P1/P2/P3 segments of the posterior cerebral artery (PCA) and responsible for the signs and symptoms of acute ischemic stroke;
* (4)Neuroimaging criteria: a) Perfusion criteria:Target mismatch profile on CT perfusion or MRI+MR perfusion (ischemic core volume \<70mL, mismatch ratio \>1.2, mismatch volume \>10mL); b) If neither MRI or CT perfusion is available at the site : an Alberta Stroke Program Early CT Score \[ASPECTS\] of 8 or more on NCCT /MRI-DWI or PC-ASPECTS of 8 or more on NCCT/MRI-DWI.
* (5)Pre-stroke modified Rankin scale (mRS) score ≤1;
* (6)Baseline National Institutes of Health Stroke Scale (NIHSS) ≥6 or NIHSS 3-5 with disabling symptoms;
* (7)Written informed consent from patients or their legally authorized representatives.

Exclusion Criteria:

* (1)Allergy to tenecteplase;
* (2)Rapidly improving symptoms at the discretion of the investigator;
* (3)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;
* (4)Intention to undergo endovascular treatment.
* (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 dabigatran can be achieved with idarucizumab; 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 or hypodensity outside the current perfusion lesion suggesting distal clot migration (secondary MeVO);
* (14)Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI;
* (15)Pregnant women, nursing mothers, or reluctance to use effective contraceptive measures during the period of the trial;
* (16)Unlikely to adhere to the trial protocol or follow-up;
* (17) Participation in other interventional clinical trials within the previous 3 months.

Where this trial is running

Beijing, Beijing Municipality and 6 other locations

• Beijing tiantan hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Jiuquan city people's hospital — Jiuquan, Gansu, China (Recruiting)
• Xingtang People's Hospital — Shijiazhuang, Hebei, China (Recruiting)
• Jiyuan Traditional Chinese Medicine Hospital — Jiyuan, Henan, China (Recruiting)
• The first people hospital of lingbao — Lingbao, Henan, China (Recruiting)
• Hai'an People's Hospital — Nantong, Jiangsu, China (Recruiting)
• The First Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Ziqi Xu — First Affiliated Hospital of Zhejiang University
• Study coordinator: Yunyun Xiong

Conditions Stroke, Ischemic; Medium Vessel Occlusions; ischemic stroke; tenecteplase; medium vessel occlusions; beyond 4.5 hours