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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)

18 de maio de 2026 atualizado por: 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.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

486

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: IVT with Tenecteplase followed by MT
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy
Medicamento: Intravenous administration
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy (MT)
Comparador Ativo: Active Comparator: MT alone
Mechanical thrombectomy alone
Procedimento: MT alone
Mechanical thrombectomy alone

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Rate of good functional outcome (independent ambulation) at 3 months
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Early neurological improvement.
Prazo: 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
Prazo: 3 months
Defined as a 3-month mRS score of 0-2
3 months
Distribution of 3-month mRS scores
Prazo: 3 months
Ordinal analysis 3-month functional outcome
3 months
One-year independent ambulation rate
Prazo: 1 year
Defined as a 1-year mRS score of 0-3.
1 year
One-year functional independence
Prazo: 1 year
Defined as a 1-year mRS score of 0-2.
1 year
Mean change in infarct volume from baseline at day 1
Prazo: Day 1
Defined as (day 1 volume) - (baseline volume).
Day 1
Early neurological worsening.
Prazo: Day 1
Defined as a ≥ 4-point increase on the NIHSS score within 24 hours due to the stroke itself.
Day 1
Intracerebral hemorrhage.
Prazo: Day 2
Intracerebral hemorrhage defined according to the Heidelberg Bleeding Classification.
Day 2
Symptomatic intracerebral hemorrhage.
Prazo: Day 2
Symptomatic intracerebral hemorrhage defined according to the Heidelberg Bleeding Classification.
Day 2
3-month mortality rate.
Prazo: 3 months
All-cause mortality.
3 months
1-year mortality rate.
Prazo: 1 year
All-cause mortality.
1 year
Medico-economic study.
Prazo: 1 year
Incremental cost utility ratio analysis.
1 year
Successful recanalisation rates
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 3 months
Type, frequency and severity of adverse events
3 months
Serious adverse events
Prazo: 3 months
Type, frequency and severity of serious adverse events
3 months

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Assistance Publique - Hôpitaux de Paris

Investigadores

  • Diretor de estudo: Gaspard GERSCHENFELD, MD, PhD, APHP

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

15 de junho de 2026

Conclusão Primária (Estimado)

1 de julho de 2029

Conclusão do estudo (Estimado)

1 de julho de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

18 de maio de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

18 de maio de 2026

Primeira postagem (Real)

22 de maio de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

22 de maio de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

18 de maio de 2026

Última verificação

1 de maio de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • APHP240911
  • 2024-520414-21-00 (Ctis)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

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.

Prazo de Compartilhamento de IPD

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

Critérios de acesso de compartilhamento IPD

Researchers who provide a methodologically sound proposal.

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • SEIVA
  • CIF

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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