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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. Mai 2026 aktualisiert von: 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.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Geschätzt)

486

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: IVT with Tenecteplase followed by MT
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy
Arzneimittel: Intravenous administration
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy (MT)
Aktiver Komparator: Active Comparator: MT alone
Mechanical thrombectomy alone
Verfahren: MT alone
Mechanical thrombectomy alone

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Rate of good functional outcome (independent ambulation) at 3 months
Zeitfenster: 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

Sekundäre Ergebnismessungen

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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Assistance Publique - Hôpitaux de Paris

Ermittler

  • Studienleiter: Gaspard GERSCHENFELD, MD, PhD, APHP

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

15. Juni 2026

Primärer Abschluss (Geschätzt)

1. Juli 2029

Studienabschluss (Geschätzt)

1. Juli 2029

Studienanmeldedaten

Zuerst eingereicht

18. Mai 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

18. Mai 2026

Zuerst gepostet (Tatsächlich)

22. Mai 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

22. Mai 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

18. Mai 2026

Zuletzt verifiziert

1. Mai 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

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

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

JA

Beschreibung des IPD-Plans

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-Sharing-Zeitrahmen

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

IPD-Sharing-Zugriffskriterien

Researchers who provide a methodologically sound proposal.

Art der unterstützenden IPD-Freigabeinformationen

  • STUDIENPROTOKOLL
  • SAFT
  • ICF

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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