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

Not Applicable

Not yet recruiting

• Conditions: Stroke, Ischemic; Medium Vessel Occlusions
• Interventions: Drug: Tenecteplase (0.25mg/kg); Drug: Standard medical treatment

• Registration Number: NCT07047014
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

Results from recent several trials provided data showing limits to the effectiveness of thrombectomy for ischemic stroke due to medium vessel occlusions.The benefit-risk profile of thrombolysis for these patients has never been investigated. We initiated a multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled trial to evaluate the efficacy and safety of tenecteplase (0.25mg/kg, maximum dose 25mg) compared to standard medical care for patients with acute ischemic stroke due to medium vessel occlusion (MeVO) within 4.5 to 24 hours from symptom onset.

Detailed Description

Adult acute ischemic stroke patients due to primary medium vessel occlusions (distal M2/M3 segments of the middle cerebral artery, A1/A2/A3 segments of the anterior cerebral artery, and P1/P2/P3 segments of the posterior cerebral artery confirmed by CTA/MRA, and responsible for the signs and symptoms of acute ischemic stroke) with baseline National Institutes of Health Stroke Scale (NIHSS) ≥6 or NIHSS 3-5 with disabling symptoms 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, mismatch volume \>10mL). We will randomly assign eligible patients to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 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 Timeline

• Study First Submitted: 2025-06-24
• Study First Submitted QC: 2025-06-24
• Status Verified: 2025-07
• Study First Posted: 2025-07-02
• Last Update Submitted: 2025-07-03
• Last Update Posted: 2025-07-09
• Study Start: 2025-07-30
• Primary Completion: 2027-03-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 596

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)Pre-stroke modified Rankin scale (mRS) score ≤1; (5)Baseline National Institutes of Health Stroke Scale (NIHSS) ≥6 or NIHSS 3-5 with disabling symptoms; (6)Neuroimaging criteria: Target mismatch profile on CT perfusion or MRI+MR perfusion (ischemic core volume <70mL, mismatch rate >1.2, mismatch volume >10mL); (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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tenecteplase (0.25 mg/kg)	Tenecteplase (0.25mg/kg)	Tenecteplase (0.25 mg/kg, max 25 mg)
Standard medical treatment	Standard medical treatment	Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone

Primary Outcome Measures

Name	Time	Method
mRS score ≤ 1 at 90 days	90 days	The proportion of patients with an mRS score ≤ 1 at 90 days

Secondary Outcome Measures

Name	Time	Method
mRS 5-6	90 days	mRS 5-6 at 90 days
mRS score at 1 year	1 year	mRS score at 1 year
mRS score	90 days	Ordinal distribution of mRS at 90 days (shift analysis)
mRS score ≤ 2	90 days	The proportion of patients with an mRS score of 0-2 at 90 days
Early neurological improvement	24 hours	The rate of early neurological improvement at 24h after randomization (defined as a NIHSS score ≤1 or ≥4 points compared with the baseline)
EuroQol 5-Dimension (EQ-5D) index	90 days and 1 year	EuroQol 5-Dimension (EQ-5D) index at 90 days and 1 year
Symptomatic intracranial hemorrhage	36 hours	Symptomatic intracranial hemorrhage within 36 hours (defined by the SITS-MOST criteria)
All-cause mortality	90 days and 1 year	All-cause mortality at 90 days and 1 year
Systemic bleeding	90 days	Systemic bleeding at 90 days (defined by the GUSTO criteria: moderate and severe bleeding)
Adverse events (AEs)/ serious adverse events (SAEs)	90 days	Adverse events (AEs)/ serious adverse events (SAEs) within 90 days

Trial Locations

Locations (2)

Beijing tiantan hospital; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China