Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Medium Vessel Occlusion

NCT07302854 | Recruiting Phase 2 DMC

• 1 other identifier: TJ-IRB202512087
• Study Type: interventional
• Target: 382
• Locations: 1 country
• Sites: 1

Brief Summary

Medium vessel occlusion (MeVO) accounts for 20-45% of acute ischemic stroke (AIS). Although patients with MeVO often present with relatively low NIHSS scores, up to one-third remain functionally dependent at follow-up despite receiving standard medical therapy, including intravenous thrombolysis. Recent randomized trials (DISTAL, ESCAPE-MeVO, DISCOUNT) have not demonstrated clinical benefit of endovascular treatment (EVT) for MeVO and have suggested higher risks of symptomatic intracranial hemorrhage and mortality, underscoring the need for safer and more targeted reperfusion strategies. Intra-arterial thrombolysis (IAT) enables localized, high-concentration thrombolytic delivery with minimal mechanical manipulation, which may be advantageous for medium and distal vessels. Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA), a genetically engineered third-generation thrombolytic agent, has shown favorable pharmacologic properties and clinical safety in AIS, including in intra-arterial use following EVT. However, prospective evidence supporting its direct therapeutic role in MeVO-related AIS remains lacking. This multicenter, prospective, open-label randomized controlled trial with blinded endpoint assessment is designed to evaluate the efficacy and safety of intra-arterial rhTNK-tPA thrombolysis in improving functional outcome in MeVO within 24 hours of symptom onset.

Conditions

Acute Ischemic Stroke; Medium Vessel Occlusion

Keywords

Acute Ischemic Stroke; medium vessel occlusion; Intra-arterial thrombolysis; Tenecteplase

Outcome Measures

Primary Outcomes (1)

• Excellent outcome

  Rate of modified Rankin scale (mRS) 0-1 at 90±7 days

  90±7 days

Secondary Outcomes (5)

• Ordinal distribution of mRS

  90±7 days

• Functional independence

  90±7 days

• Quality of life (EQ-5D-5L)

  90±7 days

• Neurologic deficit (NIHSS score) changes

  36±12 hours

• Infarct core volume change from baseline

  7±1 days or discharge if earlier

Other Outcomes (3)

• Symptomatic intracranial hemorrhage (sICH)

  48 hours

• All-caused mortality

  90±7 days

• Any intracranial hemorrhage

  48 hours

Study Arms (2)

Intervention group

EXPERIMENTAL

Patients of this group will receive intra-arterial rhTNK-tPA thrombolysis plus standard medical treatment

Procedure: Intra-arterial Thrombolysis; Drug: Standard medical treatment

Control group

ACTIVE COMPARATOR

Patients of this group will receive standard medical treatment alone

Drug: Standard medical treatment

Interventions

Intra-arterial Thrombolysis PROCEDURE

rhTNK-tPA（Tenecteplase）dose: 0.125 mg/kg, maximum dose: 12.5mg.

Intervention group

Standard medical treatment DRUG

Standard medical treatment

Control group; Intervention group

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
• Pre-stroke mRS score 0-1
• Baseline NIHSS ≥4 or symptoms deemed clearly disabling by treating physician (e.g., hemianopia, aphasia, or motor dysfunction)
• Isolated medium distal vessel occlusion (i.e., an occlusion of the co-/non-dominant M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA or the P1/P2/P3 segment of the PCA) confirmed by CT angiography (CTA) or MR angiography (MRA)
• Acute ischemic stroke within 24 hours of symptom onset, including wake-up stroke or unwitnessed stroke; The onset time of symptoms was defined as the last time of normal performance.
• Acute ischemic stroke within 6-24 hours of onset, meeting at least one of the following imaging criteria:
• Evidence of a hypoperfusion-ischemic core mismatch on CT or MRI perfusion, defined as an ischemic core volume \<50mL, hypoperfused tissue volume to ischemic core volume ratio ≥1.2, and mismatch volume ≥10 mL
• Evidence of a diffusion-hyperintensity mismatch, defined as absence of hyperintensity on fluidattenuated inversion recovery (FLAIR) imaging within ≥ 90% of the area of the diffusion weighted imaging (DWI) lesion)
• The participant or legally authorized representative is capable of providing informed consent

You may not qualify if:

• Evidence of intracranial hemorrhage
• Any active bleeding (gastrointestinal, urinary, hemorrhagic retinopathy, etc.) or parenchymal organ surgery or biopsy within 30 days before stroke; Severe head trauma or stroke within the past 3 months
• Persistent and uncontrolled hypertension, defined as systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg
• Inherited or acquired hemorrhagic tendancy; deficiency of anticoagulant factors; or on oral anticoagulant with an INR\> 1.7
• Blood glucose \<2.8 mmol/L (50 mg/dl) or \> 22.2mmol/L (400 mg/dl), platelets count \<100\*109/L, or hemoglobin \<70g/L
• Severe hepatic insufficiency, chronic hemodialysis and severe renal insufficiency (or recent blood tests suggesting a glomerular filtration rate \<30 ml/min or blood creatinine\> 200 mmol/L (2.5 mg/dl)
• Women who are pregnant or breastfeeding
• Allergy to rhTNK-tPA or radiocontrast agent
• Participation in other clinical trials
• Expected survival time less than 6 months (e.g., due to malignancy, severe cardiopulmonary disease, etc.)
• Other conditions deemed by the investigator to make the patient unsuitable for participation or pose significant risks (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorders)

Sponsors & Collaborators

• Xiang Luo: lead

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Related Publications (3)

• Miao Z, Luo G, Song L, Sun D, Chen W, Yao X, Pan Y, Liu Y, Yuan G, Wen C, Wei M, Cai X, Yang Q, Zhou Z, Chang M, Nan G, Wang J, Xiang G, Zhou L, Gao W, Zhang H, Hao J, Xu C, Sun Y, Yi T, Feng G, Han H, Gao F, Ma N, Mo D, Sun X, Deng Y, Tong X, Li X, Jia B, Wang B, He Z, Yang M, Zhao X, Zhang X, Zhang L, Li S, Tong X, Jing J, Xiong Y, Liu T, Li Z, Ren Z, Wang Y, Liebeskind DS, Jovin TG, Nguyen TN, Wang Y, Liu L, Yan B, Huo X; ANGEL-TNK Investigators. Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy: The ANGEL-TNK Randomized Clinical Trial. JAMA. 2025 Aug 19;334(7):582-591. doi: 10.1001/jama.2025.10800.

  PMID: 40616323 BACKGROUND

• Goyal M, Ospel JM, Ganesh A, Dowlatshahi D, Volders D, Mohlenbruch MA, Jumaa MA, Nimjee SM, Booth TC, Buck BH, Kennedy J, Shankar JJ, Dorn F, Zhang L, Hametner C, Nardai S, Zafar A, Diprose W, Vatanpour S, Stebner A, Bosshart S, Singh N, Sebastian I, Uchida K, Ryckborst KJ, Fahed R, Hu SX, Vollherbst DF, Zaidi SF, Lee VH, Lynch J, Rempel JL, Teal R, Trivedi A, Bode FJ, Ogungbemi A, Pham M, Orosz P, Abdalkader M, Taschner C, Tarpley J, Poli S, Singh RJ, De Leacy R, Lopez G, Sahlas D, Chen M, Burns P, Schaafsma JD, Marigold R, Reich A, Amole A, Field TS, Swartz RH, Settecase F, Lenzser G, Ortega-Gutierrez S, Asdaghi N, Lobotesis K, Siddiqui AH, Berrouschot J, Mokin M, Ebersole K, Schneider H, Yoo AJ, Mandzia J, Klostranec J, Jadun C, Patankar T, Sauvageau E, Lenthall R, Peeling L, Huynh T, Budzik R, Lee SK, Makalanda L, Levitt MR, Perry RJ, Hlaing T, Jahromi BS, Singh P, Demchuk AM, Hill MD; ESCAPE-MeVO Investigators. Endovascular Treatment of Stroke Due to Medium-Vessel Occlusion. N Engl J Med. 2025 Apr 10;392(14):1385-1395. doi: 10.1056/NEJMoa2411668. Epub 2025 Feb 5.

  PMID: 39908448 BACKGROUND

• Psychogios M, Brehm A, Ribo M, Rizzo F, Strbian D, Raty S, Arenillas JF, Martinez-Galdamez M, Hajdu SD, Michel P, Gralla J, Piechowiak EI, Kaiser DPO, Puetz V, Van den Bergh F, De Raedt S, Bellante F, Dusart A, Hellstern V, Khanafer A, Parrilla G, Morales A, Kirschke JS, Wunderlich S, Fiehler J, Thomalla G, Lemmens R, Peluso JP, Bolognese M, von Hessling A, van Es A, Kruyt ND, Coutinho JM, Castano C, Minnerup J, van Zwam W, Dhondt E, Nolte CH, Machi P, Loehr C, Mattle HP, Buhk JH, Kaesmacher J, Dobrocky T, Papanagiotou P, Alonso A, Holtmannspoetter M, Zini A, Renieri L, Keil F, van den Wijngaard I, Kagi G, Terceno M, Wiesmann M, Amaro S, Rommers N, Balmer L, Fragata I, Katan M, Leker RR, Saver JL, Staals J, Fischer U; DISTAL Investigators. Endovascular Treatment for Stroke Due to Occlusion of Medium or Distal Vessels. N Engl J Med. 2025 Apr 10;392(14):1374-1384. doi: 10.1056/NEJMoa2408954. Epub 2025 Feb 5.

  PMID: 39908430 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Xiang Luo

  Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 450001

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiang Luo, PhD, MD

CONTACT

+86-13349893413; flydottjh@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: December 24, 2025
• Study Start: December 30, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)