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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 maggio 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Stimato)

486

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: IVT with Tenecteplase followed by MT
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy
Droga: Intravenous administration
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy (MT)
Comparatore attivo: Active Comparator: MT alone
Mechanical thrombectomy alone
Procedura: MT alone
Mechanical thrombectomy alone

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Rate of good functional outcome (independent ambulation) at 3 months
Lasso di tempo: 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

Misure di risultato secondarie

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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigatori

  • Direttore dello studio: Gaspard GERSCHENFELD, MD, PhD, APHP

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

15 giugno 2026

Completamento primario (Stimato)

1 luglio 2029

Completamento dello studio (Stimato)

1 luglio 2029

Date di iscrizione allo studio

Primo inviato

18 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

18 maggio 2026

Primo Inserito (Effettivo)

22 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

22 maggio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

18 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

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

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano 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.

Periodo di condivisione IPD

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

Criteri di accesso alla condivisione IPD

Researchers who provide a methodologically sound proposal.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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Condizioni

Malattie rare

Interventi farmacologici

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