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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. maj 2026 opdateret af: 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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

486

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: IVT with Tenecteplase followed by MT
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy
Medicin: Intravenous administration
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy (MT)
Aktiv komparator: Active Comparator: MT alone
Mechanical thrombectomy alone
Procedure: MT alone
Mechanical thrombectomy alone

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Rate of good functional outcome (independent ambulation) at 3 months
Tidsramme: 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

Sekundære resultatmål

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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Assistance Publique - Hôpitaux de Paris

Efterforskere

  • Studieleder: Gaspard GERSCHENFELD, MD, PhD, APHP

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

15. juni 2026

Primær færdiggørelse (Anslået)

1. juli 2029

Studieafslutning (Anslået)

1. juli 2029

Datoer for studieregistrering

Først indsendt

18. maj 2026

Først indsendt, der opfyldte QC-kriterier

18. maj 2026

Først opslået (Faktiske)

22. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

22. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

18. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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-delingstidsramme

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

IPD-delingsadgangskriterier

Researchers who provide a methodologically sound proposal.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP
  • ICF

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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