Tenecteplase or Reteplase as Bridging Thrombolysis Before Thrombectomy in Acute Ischemic Cerebrovascular Events

NCT07748039 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: TRACEBRIDGE-2026-032025-A02
• Study Type: interventional
• Target: 1,440
• Locations: 1 country
• Sites: 5

Brief Summary

Acute ischemic stroke caused by large vessel occlusion (LVO) is a major cause of disability, and mechanical thrombectomy (MT) has become the standard treatment for eligible patients. However, the optimal role of intravenous thrombolysis before MT remains uncertain. The TRACE-BRIDGE trial is a phase 3, investigator-initiated, multicenter, randomized, open-label trial with blinded outcome assessment (PROBE design) evaluating different bridging thrombolysis strategies before MT. The trial will enroll adults with acute ischemic stroke presenting within 4.5 hours of symptom onset and with imaging-confirmed anterior circulation LVO who are eligible for intravenous thrombolysis and MT. Participants will be randomly assigned in a 1:1:1 ratio to receive tenecteplase plus MT, reteplase plus MT, or direct MT alone. The TRACE-BRIDGE trial aims to evaluate the efficacy and safety of bridging thrombolysis with tenecteplase or reteplase before mechanical thrombectomy compared with direct mechanical thrombectomy. The primary outcome is functional independence, defined as a modified Rankin Scale score of 0-2 at 90 days after randomization. If superiority of bridging thrombolysis is demonstrated, the trial will further evaluate whether reteplase is non-inferior to tenecteplase as a bridging thrombolytic strategy.

Conditions

Large Vessel Occlusion; Acute Ischemic Stroke; Anterior Circulation Brain Infarction

Keywords

acute ischemic stroke; thrombolysis; thrombectomy; tenecteplase; reteplase

Outcome Measures

Primary Outcomes (1)

• Functional Independence

  Proportion of participants achieving functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days after randomization. The mRS ranges from 0 (no symptoms) to 6 (death), with higher scores indicating greater disability.

  From randomization to 90 days after randomization (±7 days), with outcome assessment performed by blinded assessors.

Secondary Outcomes (19)

• Excellent functional outcome

  From randomization to 90 days after randomization (±7 days), with outcome assessment performed by blinded assessors.

• Favorable functional outcome

  90 days after randomization (±7 days), assessed by blinded outcome assessors.

• Early neurological improvement

  22-36 hours after randomization

• Neurological improvement

  Day 7 after randomization or discharge, whichever occurs first (±1 day)

• Pre-procedural recanalization

  During the endovascular procedure, before endovascular device manipulation

Study Arms (3)

rhTNK-tPA+MT

EXPERIMENTAL

Recombinant human TNK tissue-type plasminogen activator for injection (rhTNK-tPA) administered as a single intravenous bolus at a dose of 0.25 mg/kg (maximum dose 25 mg) within 4.5 hours of symptom onset and prior to mechanical thrombectomy, followed by standard endovascular treatment.

Drug: rhTNK-tPA (0.25mg/kg)

rPA+MT

EXPERIMENTAL

Recombinant human plasminogen activator derivative (rPA) administered as two intravenous bolus doses of 18 mg each, given over approximately 2 minutes per bolus and separated by a 30-minute interval. The first dose should be administered within 4.5 hours of symptom onset before mechanical thrombectomy. To avoid delays in reperfusion therapy, groin puncture and endovascular treatment may be initiated after administration of the first bolus without waiting for the second dose. The second bolus should be administered according to the prespecified dosing regimen unless contraindicated.

Drug: Reteplase 10 Units (U) plus a second dose of reteplase 10 U

MT alone

ACTIVE COMPARATOR

Mechanical thrombectomy performed according to standard practice without administration of intravenous thrombolytic agents.

Procedure: No thrombolysis (thrombectomy alone)

Interventions

rhTNK-tPA (0.25mg/kg) DRUG

Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) administered as a single intravenous bolus at a dose of 0.25 mg/kg (maximum dose 25 mg) within 4.5 hours of symptom onset prior to mechanical thrombectomy.

Also known as: Tenecteplase

rhTNK-tPA+MT

Reteplase 10 Units (U) plus a second dose of reteplase 10 U DRUG

Two intravenous bolus injections of 18 mg each, administered within 4.5 hours of onset over approximately 2 minutes per bolus, separated by a 30-minute interval prior to thrombectomy. To avoid delays in reperfusion therapy, groin puncture and MT procedures may be initiated after administration of the first 18 mg bolus, without waiting for completion of the second bolus. Unless contraindicated, the second rPA bolus should be administered according to the scheduled dosing regimen irrespective of EVT status.

Also known as: rPA

rPA+MT

No thrombolysis (thrombectomy alone) PROCEDURE

Patients will undergo mechanical thrombectomy according to standard practice, without administration of intravenous thrombolytic agents.

MT alone

Eligibility Criteria

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

You may qualify if:

• Patients with acute ischemic stroke presenting within 4.5 hours of symptom onset who are eligible for intravenous thrombolytic therapy. A baseline non-contrast CT or MRI is required for screening.
• Large vessel occlusion on computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) of the intracranial carotid artery (ICA) or middle cerebral artery (MCA) M1
• Age ⩾ 18 years at the time of signing the informed consent form
• ASPECTS 6-10
• Informed consent from the patients or their legal representative.

You may not qualify if:

• Intracranial hemorrhage (ICH) identified by CT or MRI
• Rapidly improving symptoms at the discretion of the investigator
• mRS \> 2 before stroke onset.
• Massive cerebral infarction (infarct size greater than one-third of the blood middle cerebral artery supply area) suggested by CT.
• Known contraindication to imaging with contrast agents
• Planned adjunct intra-arterial (IA) thrombolysis during or after endovascular treatment (EVT).
• Secondary transfer from a primary stroke center
• Any terminal illness such that patient would not be expected to survive more than one year
• 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
• Pregnant women

Sponsors & Collaborators

• Yongjun Wang: lead

Study Sites (5)

Beijing Tiantan Hospital, Capital Medical Universiity

Beijing, Beijing Municipality, 100070, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

Location

Xiangtan Central Hospital

Xiangtan, Hunan, 411100, China

Location

Rizhao Hospital of Traditional Chinese Medicine

Rizhao, Shandong, 625000, China

Location

Ya'an People's Hospital

Ya'an, Sichuan, 625000, China

Location

Related Publications (13)

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MeSH Terms

Conditions

Ischemic Stroke; Brain Infarction

Interventions

Tenecteplase; Thrombectomy

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia; 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; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Yongjun Wang

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongjun Wang, MD

CONTACT

+86 13911172565; yongjunwang@ncrcnd.org.cn

Bowei Zhang, MD

CONTACT

+86 13001139469; boweizhang@ncrcnd.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This trial is a Phase 3, investigator-initiated, Multicenter, Three-armed, Open-Label with Blinded Outcome Assessment (PROBE) Randomized Trial. All outcome measures will be assessed by investigators blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, President of Beijing Tiantan Hospital, Capital Medical University

Study Record Dates

• First Submitted: July 26, 2026
• First Posted: August 5, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: August 5, 2026

Record last verified: 2026-08

Locations

CN (5)