Endovascular Treatment With or Without Preceding Intravenous Tenecteplase (TNK) in Patients With Late-window acUte Ischemic Stroke Due to Middle Cerebral Artery Occlusion

NCT06221371 | Completed Phase 3 DMC

• 1 other identifier: CSA2023YJ003
• Study Type: interventional
• Target: 391
• Locations: 1 country
• Sites: 21

Brief Summary

The purpose of this study is to investigate the safety and efficacy of endovascular treatment with or without preceding intravenous Tenecteplase in patients with late-window (4.5-24 hours of symptom onset) acute ischemic stroke due to middle cerebral artery (MCA) M1 or proximal M2 occlusion.

Conditions

Ischemic Stroke, Acute; Thrombolysis; Endovascular Treatment

Keywords

Endovascular Treatment; Thrombolysis; Tenecteplase; Middle cerebral artery occlusion

Outcome Measures

Primary Outcomes (1)

• The modified Rankin Scale (mRS) score 0 to 2 at 90 days

  The proportion of the modified Rankin Scale (mRS) score 0 to 2 at 90 days. Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.

  90 days

Secondary Outcomes (9)

• Ordinal shift analysis of mRS at 90 days (not combined mRS 5 and 6)

  90 days

• mRS 0-1 at 90 days

  90 days

• mRS 0-3 at 90 days

  90 days

• mRS 5-6 at 90 days

  90 days

• NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization

  72 hours

Study Arms (2)

IVT with Tenecteplase+EVT

EXPERIMENTAL

Tenecteplase 0.25mg/kg: 1-2 vials (1.0×107 IU/16 mg per vial) Each vial of Tenecteplase is reconstituted with 3 ml sterile water for injection and adjusted to a concentration of 5.33 mg/ml. The total amount of drug will be calculated according to the subject's actual body weight and the required drug volume will be measured. The maximum dose should not exceed 25mg. Tenecteplase should be given as a single, intravenous bolus (drug administered over 5-10 seconds). Endovascular treatment (EVT) should be performed as soon as possible after Tenecteplase administration.

Drug: Tenecteplase

Direct EVT

ACTIVE COMPARATOR

During the study period, NMPA-approved stents are permitted. EVT included thrombectomy with stent retrievers, thromboaspiration, intraarterial thrombolysis, balloon angioplasty, stenting, or a combination of these approaches at the discretion of the interventional team.

Device: direct EVT

Interventions

Tenecteplase DRUG

Tenecteplase (0.25 mg/kg, maximum dose 25mg) is given as a single, intravenous bolus (injection over 5 to 10 seconds) immediately upon randomization. EVT should be performed as soon as possible after Tenecteplase administration.

IVT with Tenecteplase+EVT

direct EVT DEVICE

During the study period, NMPA-approved stents are permitted. EVT included thrombectomy with stent retrievers, thromboaspiration, intraarterial thrombolysis, balloon angioplasty, stenting, or a combination of these approaches at the discretion of the interventional team.

Direct EVT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥18 years old;
• Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment including wake-up stroke and unwitnessed stroke; onset time refers to 'last seen well time';
• MCA-M1 or proximal M2 occlusions confirmed by Computer Tomography Angiography (CTA)/Magnetic Resonance Angiography (MRA) that was responsible for signs and symptoms of acute ischemic stroke;
• Neuroimaging: target mismatch profile on CT perfusion (CTP) or MRI + MR perfusion imaging (MRP) (analyzed by perfusion analysis software with Class II and above medical device certificates) \[ischemic core volume (defined as CBF\<30% or apparent diffusion coefficient value \< 620×10-6 mm2/s) \<70mL, mismatch ratio≥1.8, mismatch volume≥15mL\];
• Pre-morbid mRS score ≤2;
• Baseline NIHSS 6-25 (both included);
• Written informed consent from patients or their legally authorized representative.

You may not qualify if:

• Patients who decline interventional therapy or intravenous thrombolysis (IVT)；
• Patients allergic to tenecteplase；
• Rapidly improving symptoms at the discretion of the investigators；
• NIHSS consciousness score 1a\>2, or epileptic seizure, hemiplegia after seizures or combined with other nervous/mental illness not able to cooperate or unwilling to cooperate；
• Persistent blood pressure elevation (systolic \> 185 mmHg or diastolic \>110 mmHg), despite blood pressure lowering treatment；
• Blood glucose \< 2.8 or \> 22.2 mmol/L (point of care glucose testing is acceptable)；
• Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days；
• Any known impairment in coagulation, e.g.: If on vitamin K antagonists, then INR \>1.7 or prothrombin time \>15 seconds; if use of any direct thrombin inhibitors or new oral anticoagulants (NOACs) during the last 48 hours unless reversal of effect can be achieved with idarucizumab; values in sensitivity laboratory tests exceed the upper limit of normal \[including activated partial thromboplastin time (APTT), international normalized ratio (INR), platelet count, thrombin time (TT), or appropriate factor Xa activity assays, etc.\]; if on heparin during the last 24 hours or with an elevated aPTT greater than the upper limit of normal；
• Known defect of platelet function or platelet count below 100\*109/L (patients on antiplatelet agents can be included)；
• Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury, intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm (excluding neuroectodermal tumors such as meningioma), arteriovenous malformation or giant aneurysm；
• Patients who would not be expected to survive more than 1 year；
• Unable to perform CTP or MRP；
• Large infarct on non-contrast CT brain or MRI (infarct size \>1/3 MCA territory)；
• Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid haemorrhage, and subdural / extradural hematoma；
• Multiple arterial occlusions (bilateral MCA occlusion, MCA occlusion accompanied by basilar artery occlusion)；

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Linyi People's Hospital: collaborator

Study Sites (21)

The First Affiliated Hospital of USTC

Hefei, Anhui, China

Location

First Affiliated Hospital of Wannan Medical College

Wuhu, Anhui, China

Location

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

Beijing Daxing District People's Hospital

Beijing, Beijing Municipality, China

Location

The 2nd affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Location

Puyang Oilfield General Hospital

Puyang, Henan, China

Location

People's Hospital of Queshan

Zhumadian, Henan, China

Location

First People's Hospital of Chenzhou

Chenzhou, Hunan, 423000, China

Location

Dalian Municipal Central Hospital

Dalian, Liaoning, China

Location

First Affiliated Hospital of Xi 'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Heze Municipal Hospital

Heze, Shandong, 274400, China

Location

Jining NO.1 People's Hospital

Jining, Shandong, China

Location

Liaocheng Third People's Hospital

Liaocheng, Shandong, 252006, China

Location

Linyi People's Hospital

Linyi, Shandong, 276003, China

Location

Linyi Central Hospital

Linyi, Shandong, China

Location

Qingdao Central Hospital

Qingdao, Shandong, 266000, China

Location

Rizhao People's Hospital

Rizhao, Shandong, 276800, China

Location

Rizhao Traditional Chinese Medicine Hospital

Rizhao, Shandong, 276800, China

Location

Weifang People's Hospital

Weifang, Shandong, China

Location

Zaozhuang Municipal Hospital

Zaozhuang, Shandong, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Ischemic Stroke; Infarction, Middle Cerebral Artery

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Fengyuan Che, MD

  Linyi People's Hospital

  PRINCIPAL INVESTIGATOR

• Yunyun Xiong, MD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: blinded-endpoint
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A multi-center, prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: January 24, 2024
• Study Start: January 25, 2024
• Primary Completion: October 13, 2025
• Study Completion: October 13, 2025
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

CN (21)