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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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

486

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：IVT with Tenecteplase followed by MT
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy
薬：Intravenous administration
Intravenous administration of Tenecteplase (0.25 mg/kg, maximum 25 mg) followed by mechanical thrombectomy (MT)
アクティブコンパレータ：Active Comparator: MT alone
Mechanical thrombectomy alone
手順：MT alone
Mechanical thrombectomy alone

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Rate of good functional outcome (independent ambulation) at 3 months
時間枠：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

二次結果の測定

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Assistance Publique - Hôpitaux de Paris

捜査官

  • スタディディレクター：Gaspard GERSCHENFELD, MD, PhD、APHP

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年6月15日

一次修了 (推定)

2029年7月1日

研究の完了 (推定)

2029年7月1日

試験登録日

最初に提出

2026年5月18日

QC基準を満たした最初の提出物

2026年5月18日

最初の投稿 (実際)

2026年5月22日

学習記録の更新

投稿された最後の更新 (実際)

2026年5月22日

QC基準を満たした最後の更新が送信されました

2026年5月18日

最終確認日

2026年5月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

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

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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 共有時間枠

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

IPD 共有アクセス基準

Researchers who provide a methodologically sound proposal.

IPD 共有サポート情報タイプ

  • STUDY_PROTOCOL
  • SAP
  • ICF

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米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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