Tenecteplase or Reteplase as Bridging Thrombolysis Before Thrombectomy in Acute Ischemic Cerebrovascular Events (TRACE-BRIDGE): A Multicenter, Randomized, Open-Label, Three-Arm, Blinded-Endpoint Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- Yongjun Wang
- 入组人数
- 1,440
- 试验地点
- 5
- 主要终点
- Functional Independence
研究概览
简要总结
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.
详细描述
Mechanical thrombectomy (MT) has become the standard of care for eligible patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Randomized controlled trials and individual patient-level meta-analyses have demonstrated substantial improvements in functional outcomes with MT compared with medical management alone.
However, the optimal strategy for intravenous thrombolysis before mechanical thrombectomy remains uncertain. Previous randomized trials evaluating bridging thrombolysis have primarily investigated alteplase, and the additional clinical benefit of intravenous thrombolysis before MT compared with direct MT has not been conclusively established.
Tenecteplase and reteplase are two thrombolytic agents that may provide potential alternatives to alteplase in the bridging thrombolysis setting. Tenecteplase, administered at a dose of 0.25 mg/kg, has demonstrated promising efficacy and safety profiles in patients with acute ischemic stroke, with increasing evidence supporting its use as a bridging thrombolytic agent before MT. Reteplase, administered as two intravenous bolus doses of 18 mg, has also shown potential as an alternative thrombolytic agent and requires further evaluation in patients undergoing MT.
The TRACE-BRIDGE trial is a phase 3, investigator-initiated, multicenter, randomized, open-label trial with blinded outcome assessment (PROBE design). The trial will enroll adults with acute ischemic stroke who present within 4.5 hours of symptom onset and have imaging-confirmed anterior circulation large vessel occlusion. Participants must meet predefined eligibility criteria for intravenous thrombolysis and mechanical thrombectomy. Eligible participants will be randomly assigned in a 1:1:1 ratio to receive tenecteplase plus MT, reteplase plus MT, or direct MT alone. The primary outcome is functional independence, defined as a modified Rankin Scale score of 0-2 at 90 days after randomization.
The primary objective of the trial is to determine whether bridging thrombolysis with tenecteplase or reteplase, analyzed as a combined treatment strategy, is superior to direct mechanical thrombectomy alone in achieving functional independence at 90 days. If superiority is established, the trial will further evaluate whether reteplase is non-inferior to tenecteplase as a bridging thrombolytic strategy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
rhTNK-tPA+MT
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.
干预措施: rhTNK-tPA (0.25mg/kg) (Drug)
rPA+MT
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.
干预措施: Reteplase 10 Units (U) plus a second dose of reteplase 10 U (Drug)
MT alone
Mechanical thrombectomy performed according to standard practice without administration of intravenous thrombolytic agents.
干预措施: No thrombolysis (thrombectomy alone) (Procedure)
结局指标
主要结局
Functional Independence
时间窗: From randomization to 90 days after randomization (±7 days), with outcome assessment performed by blinded assessors.
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.
次要结局
- 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)
- Near-complete reperfusion post endovascular treatment(At the end of the endovascular procedure (immediately after completion of the procedure))
- Successful reperfusion post endovascular Treatment(At the end of the endovascular procedure (immediately after completion of the procedure))
- First-pass reperfusion(Immediately after the first thrombectomy pass during the endovascular procedure)
- Modified first-pass reperfusion(Immediately after the first thrombectomy pass during the endovascular procedure)
- Health Related Quality of Life(90 days after randomization (±7 days))
- Barthel index≥95(90 days after randomization (±7 days))
- Symptomatic intracranial hemorrhage(Up to 36 hours from randomization)
- Parenchymal Hematoma Type 2(Up to 36 hours from randomization)
- Adverse events, serious adverse events, and suspected unexpected serious adverse reactions(90 days after randomization (±7 days))
- Procedure-related complications(From the start of the endovascular procedure to 7 days after randomization)
- Major Bleeding(90 days after randomization (±7 days))
- Clinically relevant non-major bleeding(90 days after randomization (±7 days))
- All-cause mortality at 7 days(Within 7 days after randomization)
- All-cause mortality at 90 days(90 days after randomization (±7 days))
研究者
Yongjun Wang
Professor, President of Beijing Tiantan Hospital, Capital Medical University
Beijing Tiantan Hospital