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Intravenous Thrombolysis With Tenecteplase Plus Thrombectomy Versus Thrombectomy Alone In Patients With A Large Ischemic Stroke: A Multicenter Randomized Controlled Trial (IVT-ALL-IN) (IVT-ALL-IN)

2026年5月18日 更新者：Assistance Publique - Hôpitaux de Paris

Stroke is a frequent and severe disease worldwide, representing the second leading cause of death and the leading cause of acquired disability. Over the last thirty years, reperfusion therapies have transformed the prognosis of ischemic stroke. For patients with acute ischemic stroke due to large-vessel occlusion (LVOS) and a small- to moderate-sized irreversibly injured tissue (core), the recommended treatment consists of intravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT). However, for the fifth of LVOS patients with large core, MT has demonstrated its effectiveness, but the benefits of prior IVT remain unclear. In fact, no randomized trial has compared IVT+MT and MT alone in this population.

Tenecteplase is increasingly replacing alteplase for LVOS due to two key advantages. First, it is administered as a single intravenous bolus, which speeds up treatment and transfers. Second, it improves reperfusion and functional outcomes in LVOS patients without large core. Emerging real-world evidence with tenecteplase reports lower rates of symptomatic intracranial hemorrhage than alteplase, suggesting superior overall efficacy. To date, no randomized trial has explored the benefit of tenecteplase in LVOS patients with large core.

The IVT ALL IN trial is a French multicenter open randomized controlled trial with two parallel groups (IVT with tenecteplase followed by MT [IVT+MT] vs MT alone) and blinded endpoint assessment following a PROBE design. Its main objective is to assess which treatment strategy between IVT+MT and MT alone has a superior efficacy in terms of 3-month good functional outcome, defined as a modified Rankin scale (mRS) score ≤ 3 at 3 months, for LVOS patients with large core of the anterior circulation. Our trial will provide high-level evidence on the optimal reperfusion treatment strategy for LVOS patients with large ischemic core, who currently still have a low likelihood of achieving a favorable neurological outcome.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

The IVT ALL IN trial is a French multicenter open-label randomized controlled trial with two parallel groups and blinded endpoint assessment following a PROBE design. Patients will be randomized between two treatment groups: the IVT with tenecteplase followed by MT group (IVT+MT; experimental group) or the MT alone group (control group). Randomization will be minimized on center, core size (very large [ASPECTS 2-3] versus large [ASPECT 4-5] infarcts) and treatment time window (within 4.5 hours vs others).

We plan to include 486 adult patients with a pre-stroke mRS ≤ 1 presenting an anterior circulation LVOS eligible to MT within 24 hours of onset, or unknown onset with a DWI-FLAIR mismatch, with a large core defined as:

  • ASPECTS 2-5 or a core volume between 70 and 130 ml on MRI or perfusion CT for patients with process times compatible with IVT administration within 4.5 hours of onset or unknown onset with process times compatible with IVT administration within 4.5 hours of last seen well or unknown onset with a DWI-FLAIR mismatch
  • ASPECTS 2- 5 with a core volume ≤ 70 ml and core/perfusion mismatch > 1.2 for patients with process times compatible with IVT administration within 4.5 and 9 hours of onset, defined as the mid-point between last known to be normal and symptoms constatation in case of unknown onset

The primary endpoint is the rate of good functional outcome (independent ambulation) at 3 months defined as a modified Rankin scale (mRS) score of 0-3.

In the six recently published trials comparing MT to best medical management for LVOS patients with large ischemic cores, rates of 3-month independent ambulation (mRS ≤ 3) range from 30% to 47% with a weighted average around 38%. In the first 5 RCTs that focused on the benefit of MT in LVOS, the minimal difference observed with MT was 13%. With these assumptions and for a global alpha risk of 0.05, a power of 0.8 and a bilateral test, the total number of patients to randomize would be 486 patients (243 in each arm) to increase the rate of good functional outcomes from 38% in the control group to 51% in the experimental group accounting for 5% of lost to follow-up and considering one interim analysis and the final analysis using a Lan and Demets method with an O'Brien & Fleming type alpha risk expenditure function We plan a sequential analysis of the primary outcome with 2 analyses: one interim analysis after the evaluation of the primary outcome for one third of the planned number of participants randomized, and a final analysis at the end of the study (end of follow-up of the last randomized participant). This sequential analysis is planned to be able to stop the trial in case of a large difference between the 2 groups or for futility if the conditional power is too low. It is planned according to the Lan & DeMets approach with a control of alpha risk according to the method of O'Brien & Flemming.

研究类型

介入性

注册 (估计的)

486

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 法国
      • Aix-en-Provence、法国、13100
        • CH Pays d'Aix - Site d'Aix-en-Provence
        • 首席研究员：
          • Silvia DI EGGE
      • Besançon、法国、25030
        • CHU Besançon
        • 首席研究员：
          • Guillaume CHARBONNIER
      • Bordeaux、法国、33076
        • CHU Bordeaux - Groupe Hospitalier Pellegrin
        • 首席研究员：
          • Igor Sibon
      • Brest、法国、29609
        • CHU Brest - Hôpital de La Cavale Blanche
        • 首席研究员：
          • Serge TIMSIT
      • Bron、法国、69500
        • HCL - Hôpital Pierre Wertheimer
        • 首席研究员：
          • Tae-Hee Cho
      • Caen、法国、14000
        • CHU Caen Normandie
        • 首席研究员：
          • Marion BOULANGER
      • Corbeil-Essonnes、法国、91106
        • Ch Sud Francilien
        • 首席研究员：
          • Nicolas CHAUSSON
      • Créteil、法国、94000
        • AP-HP - Hôpital Henri Mondor-Albert Chenevier
        • 首席研究员：
          • Aymeric WITTWER
      • Dijon、法国、21079
        • CHU Dijon Bourgogne
        • 首席研究员：
          • Yannick BEJOT
      • Gonesse、法国、95500
        • CH Gonesse
        • 首席研究员：
          • Eric MANCHON
      • Grenoble、法国、38043
        • CHU Grenoble Alpes - Site Nord
        • 首席研究员：
          • Olivier DETANTE
      • Le Chesnay、法国、78000
        • CH Versailles - Hôpital André Mignot
        • 首席研究员：
          • Fernando PICO
      • Le Kremlin-Bicêtre、法国、94275
        • AP-HP - Hôpital Bicêtre
        • 首席研究员：
          • Laura VENDITTI
      • Lille、法国、59000
        • CHU Lille - Hôpital Roger Salengro
        • 首席研究员：
          • Lucie DELLA SCHIAVA
      • Limoges、法国、87042
        • CHU Limoges - Hôpital Dupuytren
        • 首席研究员：
          • Francisco MACIAN-MONTORO
      • Marseille、法国、13005
        • AP-HM - Hopital de la Timone
        • 首席研究员：
          • Laurent SUISSA
      • Montpellier、法国、34295
        • CHU MONTPELLIER - Hôpital Saint-Eloi
        • 首席研究员：
          • Caroline ARQUIZAN
      • Nancy、法国、54035
        • CHRU Nancy - Hôpital central
        • 首席研究员：
          • Sébastien Richard
      • Nantes、法国、44093
        • CHU Nantes - Hopital Nord Laënnec
        • 首席研究员：
          • Benoit GUILLON
      • Nice、法国、6000
        • CHU Nice - Hôpital Pasteur
        • 首席研究员：
          • Barbara CASOLLA
      • Paris、法国、75019
        • Fondation Adolphe de Rothschild
        • 首席研究员：
          • Michael OBADIA
      • Paris、法国、75013
        • Hôpital Pitié-Salpêtrière
        • 首席研究员：
          • Gaspard GERSCHENFELD
      • Paris、法国、75018
        • AP-HP - Hôpital Bichat
        • 首席研究员：
          • Philippa LAVALLEE
      • Paris、法国、75010
        • AP-HP - Hôpital Lariboisiere-Fernand Widal
        • 首席研究员：
          • Elodie BERTHET
      • Paris、法国、75014
        • GH Paris Saint-Joseph - Hôpital Paris Saint-Joseph
        • 首席研究员：
          • Benjamin MAYER
      • Paris、法国、75014
        • GHU Paris Psychiatrie et Neurosciences - Hôpital Sainte-Anne
        • 首席研究员：
          • Guillaume TURC
      • Perpignan、法国、66046
        • CH Perpignan
        • 首席研究员：
          • Denis Sablot
      • Poitiers、法国、86000
        • CHU Poitiers - Hôpital de La Milétrie
      • Reims、法国、51100
        • CHU Reims - Hôpital Maison Blanche
        • 首席研究员：
          • Solène MOULIN
      • Rennes、法国、35033
        • CHU Rennes - Hôpital Pontchaillou
        • 首席研究员：
          • Stéphane VANNIER
      • Rouen、法国、76031
        • CHU Rouen - Hôpital Charles-Nicolle
        • 首席研究员：
          • Florian BASILLE
      • Saint-Denis、法国、93200
        • CH Saint-Denis - Hôpital Delafontaine
        • 首席研究员：
          • Carole HENRY
      • Saint-Etienne、法国、42055
        • CHU Saint-Etienne - Hôpital Nord
        • 首席研究员：
          • Pierre GARNIER
      • Strasbourg、法国、67098
        • Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
        • 首席研究员：
          • Valérie Wolff
      • Suresnes、法国、92150
        • Hôpital Foch
        • 首席研究员：
          • Bertrand Lapergue
      • Tours、法国、37000
        • CHRU Tours - Hôpital Bretonneau
        • 首席研究员：
          • Marco PASI

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion criteria :

  • Age ≥ 18 years
  • mRS ≤ 1 before stroke
  • Anterior circulation large vessel occlusion stroke eligible to mechanical thrombectomy (MT) within 24 hours of onset or unknown onset with a DWI-FLAIR mismatch

  • Large core defined either as:

    • ASPECTS 2-5 or a core volume between 70 and 130 ml on MRI or perfusion CT for patients with process times compatible with IVT administration within 4.5 hours of onset or unknown onset with process times compatible with IVT administration within 4.5 hours of last seen well or unknown onset with a DWI-FLAIR mismatch
    • ASPECTS 2- 5 with a core volume ≤ 70 ml and core/perfusion mismatch > 1.2 for patients with process times compatible with IVT administration within 4.5 and 9 hours of onset, defined as the mid-point between last known to be normal and symptoms constatation in case of unknown onset
  • Written informed consent signed by the patient or the trustworthy person / family member / close relative, or inclusion in case of emergency (to note, written informed consent will be signed by the patient (if needed, by trustworthy person, family member or close relative) as soon as possible (article 35 of the European regulation N°536/2014))

Exclusion criteria :

  • Anterior circulation stroke with a distal occlusion not eligible to MT

    • Posterior circulation stroke
    • Pregnancy or breastfeeding woman

    • Any contraindication to IVT, based on the Metalyse SmPC and the latest AHA/ASA guidelines on IVT (Prabhakaran et al. Stroke. 2026), other than those related to the NIHSS score upper limit, infarct size and symptoms-to-onset time, such as (but not limited to):

      • Persistent incapacity to lower blood pressure under 185/110 mmHg
      • Respiratory or hemodynamic failure
      • Externalized bleeding
      • Hypersensitivity to the active substance or to any of its excipients
      • Hypersensitivity to gentamicin (a trace residue from the manufacturing process
      • Known haemorrhagic diathesis
      • Bacterial endocarditis, pericarditis
      • Acute pancreatitis
      • Significant impairment of hepatic function, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and progressive hepatitis
      • Active ulcerative gastrointestinal disease
      • Neoplasia associated with an increased risk of haemorrhage
      • Known bleeding disorders, such as thrombocytopenia (platelet count < 100 G/L) or severe coagulopathy (INR > 1.7, activated partial thromboplastin time > 40s or prothrombin time > 15s) either currently or within the last 3 weeks
      • Treatment with effective doses of oral anticoagulants (e.g. vitamin K antagonists with an INR > 1.7)
      • Any history of intracerebral neoplasm
      • History of intracranial / spinal surgery or acute spinal cord injury within 3 months
      • Recent ST-segment elevation myocardial infarction within 3 months
      • Major non-central nervous system surgery, biopsy of a parenchymal organ or significant trauma within the last 10 days
      • Recent moderate to severe traumatic brain injury
      • Known arterial or venous malformation, except unruptured intracranial aneurysm
      • History of intracerebral haemorrhage within 3 months
      • Known cerebral amyloid angiopathy
      • History of acute ischaemic stroke within 3 months

  • Any contra-indication to MT:

    • Contra-indication to femoral, radial or humeral arterial puncture
    • Allergy to iodinated contrast media

    • Known Renal insufficiency at inclusion time (confirmed biologically by a creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula)

      • Anticipated life expectancy of less than 3 months
      • Participation in another interventional clinical trial evaluating a health product or any randomized clinical trial
      • Absence of affiliation to National French social security system
      • Under legal protection measure (tutorship or curatorship) and patient deprived of freedom

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：IVT with Tenecteplase followed by MT
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy
药品：Intravenous administration
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy (MT)
有源比较器：Active Comparator: MT alone
Mechanical thrombectomy alone
程序：MT alone
Mechanical thrombectomy alone

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Rate of good functional outcome (independent ambulation) at 3 months
大体时间：3 months

defined as a modified Rankin scale (mRS) score of 0-3. mRS scores will be determined by certified raters unaware of the treatment arm or baseline characteristics of the individual patient by in person interview or, if not possible, by telephone.

The Modified Rankin Scale (mRS) measures degree of disability/dependence after a stroke.

Scores range from 0 to 6 (death)
3 months

次要结果测量

结果测量
措施说明
大体时间
Early neurological improvement.
大体时间：D1

Defined as a ≥ 8-points decrease of the NIHSS score or a NIHSS score ≤ 1 at day 1.

National Institutes of Health Stroke Scale (NIHSS) is a questionnaire to evaluate neurologic outcome and degree of recovery for patients with stroke.

Scores range from 0 to 42 (worse)
D1
3-month functional independence rate
大体时间：3 months
Defined as a 3-month mRS score of 0-2
3 months
Distribution of 3-month mRS scores
大体时间：3 months
Ordinal analysis 3-month functional outcome
3 months
One-year independent ambulation rate
大体时间：1 year
Defined as a 1-year mRS score of 0-3.
1 year
One-year functional independence
大体时间：1 year
Defined as a 1-year mRS score of 0-2.
1 year
Mean change in infarct volume from baseline at day 1
大体时间：Day 1
Defined as (day 1 volume) - (baseline volume).
Day 1
Early neurological worsening.
大体时间：Day 1
Defined as a ≥ 4-point increase on the NIHSS score within 24 hours due to the stroke itself.
Day 1
Intracerebral hemorrhage.
大体时间：Day 2
Intracerebral hemorrhage defined according to the Heidelberg Bleeding Classification.
Day 2
Symptomatic intracerebral hemorrhage.
大体时间：Day 2
Symptomatic intracerebral hemorrhage defined according to the Heidelberg Bleeding Classification.
Day 2
3-month mortality rate.
大体时间：3 months
All-cause mortality.
3 months
1-year mortality rate.
大体时间：1 year
All-cause mortality.
1 year
Medico-economic study.
大体时间：1 year
Incremental cost utility ratio analysis.
1 year
Successful recanalisation rates
大体时间：Day 1
Defined as a modified Treatment In Cerebral Ischemia (mTICI) scores of 2b50/2b67/2c/3 on the first angiographic run, after the first pass and at the end of the procedure
Day 1
Excellent recanalisation rates
大体时间：Day 1
Defined as a modified Treatment In Cerebral Ischemia (mTICI) scores of 2c/3 respectively on the first angiographic run, after the first pass and at the end of the procedure
Day 1
Complete recanalisation rates
大体时间：Day 1
Defined as a modified Treatment In Cerebral Ischemia (mTICI) scores of 3 respectively on the first angiographic run, after the first pass and at the end of the procedure
Day 1
Adverse events
大体时间：3 months
Type, frequency and severity of adverse events
3 months
Serious adverse events
大体时间：3 months
Type, frequency and severity of serious adverse events
3 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Assistance Publique - Hôpitaux de Paris

调查人员

  • 研究主任：Gaspard GERSCHENFELD, MD, PhD、APHP

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年6月15日

初级完成 (估计的)

2029年7月1日

研究完成 (估计的)

2029年7月1日

研究注册日期

首次提交

2026年5月18日

首先提交符合 QC 标准的

2026年5月18日

首次发布 (实际的)

2026年5月22日

研究记录更新

最后更新发布 (实际的)

2026年5月22日

上次提交的符合 QC 标准的更新

2026年5月18日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • APHP240911
  • 2024-520414-21-00 (克蒂斯)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

IPD 共享时间框架

Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor

IPD 共享访问标准

Researchers who provide a methodologically sound proposal.

IPD 共享支持信息类型

  • 研究方案
  • 树液
  • 国际碳纤维联合会

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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