Clinical trial • Phase III • Cardiology|Neurology

Alteplase for Acute ischemic stroke (anterior circulation large vessel occlusion)

Phase III trial of Alteplase for Acute ischemic stroke (anterior circulation large vessel occlusion).

Overview

Trial Therapeutic Area
Cardiology|Neurology
Trial Disease
Acute ischemic stroke (anterior circulation large vessel occlusion)
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
01-06-2024
First CTIS Authorization Date
12-09-2024

Trial design

Randomised, open-label, control group: no ia thrombolysis after ivt alone, bridging therapy (ivt + mt), or mt alone (according to standard of care). experimental group: adjunct ia thrombolysis after ivt alone, bridging therapy (ivt + mt), or mt alone. Phase III trial across 27 sites in France.

Randomised
Yes
Open Label
Yes
Comparator
Control group: no IA thrombolysis after IVT alone, bridging therapy (IVT + MT), or MT alone (according to standard of care). Experimental group: adjunct IA thrombolysis after IVT alone, bridging therapy (IVT + MT), or MT alone.
Target Sample Size
626
Trial Duration For Participant
365

Eligibility

Recruits 626 Vulnerable population selected (isVulnerablePopulationSelected = true). Subject information and informed consent forms available for Patient (Initial and Continuation) and for 'Proche' (relative/proxy), indicating provisions for proxy/relative involvement in consent..

Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Subject information and informed consent forms available for Patient (Initial and Continuation) and for 'Proche' (relative/proxy), indicating provisions for proxy/relative involvement in consent.

Inclusion criteria

  • {"criterion_text":"- Pre-stroke mRS 0-2\n- Acute ischemic stroke with anterior circulation LVO defined as intracranial internal carotid artery, M1, or M2 occlusion proven on CT or MRI\n- NIHSS score ≥ 5 at admission\n- eTICI 2b-2c-3 after IVT alone, bridging therapy (IVT + MT), or MT alone and confirmed by catheter angiogram"}

Exclusion criteria

  • {"criterion_text":"- Contraindications for IA thrombolysis: Platelet count <100 000/mm3, INR >1.7, AOD use <48h or biological confirmation of activity and effective heparin treatment\n- Intracerebral hemorrhage\n- Occlusion or high grade stenosis treated by stenting\n- Patient expected to be unable to present or be available for 3-month visit follow-up"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is the severity of disability according to the shift of scores on the modified Rankin Scale (mRS) at 90 (±15) days.","definition_or_measurement_approach":"Shift in modified Rankin Scale (mRS) score measured at 90 days (±15 days)."}

Secondary endpoints

  • {"endpoint_text":"- 1a) EFFICACY: -Distribution of the mRS score at day 90 (±15).","definition_or_measurement_approach":"Distribution of mRS scores at day 90 (±15 days)."}
  • {"endpoint_text":"- 1a) EFFICACY: -Excellent functional outcome (mRS 0-1) at 90 (±15) day.","definition_or_measurement_approach":"Proportion of participants with mRS 0-1 at 90 (±15 days)."}
  • {"endpoint_text":"- 1a) EFFICACY: -Functional independence (mRS 0-2) at 90 (±15) day.","definition_or_measurement_approach":"Proportion of participants with mRS 0-2 at 90 (±15 days)."}
  • {"endpoint_text":"- 1a) EFFICACY: -Early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) score by at least 8 points, or NIHSS score of 0-1) at 24 (±6) hours.","definition_or_measurement_approach":"Change in NIHSS at 24 (±6) hours: reduction ≥8 points or NIHSS 0-1."}
  • {"endpoint_text":"- 1a) EFFICACY: -eTICI at the end of endovascular procedure (including IA thrombolysis in the intervention group).","definition_or_measurement_approach":"eTICI grade assessed at the end of the endovascular procedure."}
  • {"endpoint_text":"- 1a) EFFICACY: -Infarct growth: difference in (i) ASPECTS scores and (ii) infarct core volume (MRI DWI or CT perfusion) between 24 (±6) hours and baseline","definition_or_measurement_approach":"Difference in ASPECTS and infarct core volume (MRI DWI or CT perfusion) between baseline and 24 (±6) hours."}
  • {"endpoint_text":"- 1b) SAFETY: -Complications during endovascular treatment: arterial perforation, extracranial carotid dissection, embolization in a new territory.","definition_or_measurement_approach":"Occurrence of listed procedural complications during endovascular treatment."}
  • {"endpoint_text":"- 1b) SAFETY: -Symptomatic and asymptomatic intracerebral hemorrhage within 24-hour on CT or MRI, according to the Heidelberg classification (imaging core laboratory).","definition_or_measurement_approach":"Intracerebral hemorrhage within 24 hours assessed by CT/MRI and classified per Heidelberg classification (central imaging core lab review)."}
  • {"endpoint_text":"- 1b) SAFETY: -Extracranial hemorrhage requiring transfusion, surgery or resulting in death","definition_or_measurement_approach":"Occurrence of extracranial hemorrhage requiring transfusion, surgery, or resulting in death."}
  • {"endpoint_text":"- 1b) SAFETY: -Death from all causes within 90 (±15) days","definition_or_measurement_approach":"All-cause mortality within 90 (±15) days."}
  • {"endpoint_text":"- 2) COST EFFECTIVENESS: Incremental cost-effectiveness and cost-utility ratios of a strategy based on adjunct IA thrombolysis in case of successful angiographic reperfusion compared with a strategy of no adjunct IA thrombolysis.","definition_or_measurement_approach":"Economic evaluation calculating incremental cost-effectiveness and cost-utility ratios comparing strategies with and without adjunct IA thrombolysis."}
  • {"endpoint_text":"- 3) TOTAL COST: Total cost of each treatment strategy and net impact on the National Health Insurance System (difference in costs).","definition_or_measurement_approach":"Total cost per treatment strategy and difference in costs (budget impact) on the National Health Insurance System."}

Recruitment

Planned Sample Size
626
Recruitment Window Months
48
Consent Approach
Subject information and informed consent forms provided for Patient (Initial and Continuation) and for 'Proche' (relative/proxy). Consent documents available as L1_ICF_Patient_Initial, L1_ICF_Patient_Poursuite, L1_ICF_Proche_Initial, L1_ICF_Proche_Poursuite and related information sheets; indicates consent from patient or proxy/relative where applicable. No explicit age-specific assent documents or languages stated in the record.

Geography

Total Number Of Sites
27
Total Number Of Participants
626

France

Earliest CTIS Part Ii Submission Date
03-09-2024
Latest Decision Or Authorization Date
16-04-2025
Processing Time Days
225
Number Of Sites
27
Number Of Participants
626

Sites

Site Name
Besancon University Hospital Center
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Guillaume CHARBONNIER
Principal Investigator Email
Guillaume.charbonnier@univ-fcomte.fr
Contact Person Name
Guillaume CHARBONNIER
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Neuroradiologie diagnostique et thérapeutique
Principal Investigator Name
Anne-Christine JANUEL
Principal Investigator Email
Januel.ac@chu-toulouse.fr
Contact Person Name
Anne-Christine JANUEL
Contact Person Email
Januel.ac@chu-toulouse.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Neuroradiologie Diagnostique et Thérapeutique
Principal Investigator Name
Cyril DARGAZANLI
Principal Investigator Email
c-dargazanli@chu-montpellier.fr
Contact Person Name
Cyril DARGAZANLI
Site Name
Centre Hospitalier De La Cote Basque
Department Name
Radiology Diagnostique
Principal Investigator Name
Louis VEUNAC
Principal Investigator Email
lveunac@ch-cotebasque.fr
Contact Person Name
Louis VEUNAC
Contact Person Email
lveunac@ch-cotebasque.fr
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Neuroradiologie Diagnostique et Interventionnelle
Principal Investigator Name
Emmanuel CHABERT
Principal Investigator Email
echabert@chu-clermontferrand.fr
Contact Person Name
Emmanuel CHABERT
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Frédéric CLARENCON
Principal Investigator Email
frederic.clarencon@aphp.fr
Contact Person Name
Frédéric CLARENCON
Contact Person Email
frederic.clarencon@aphp.fr
Site Name
HIA Sainte Anne
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Quentin HOLAY
Principal Investigator Email
qholay@gmail.com
Contact Person Name
Quentin HOLAY
Contact Person Email
qholay@gmail.com
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Victor DUMAS
Principal Investigator Email
Victor.dumas@chu-poitiers.fr
Contact Person Name
Victor DUMAS
Contact Person Email
Victor.dumas@chu-poitiers.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Radiologie interventionnelle
Principal Investigator Name
Cyril CHIVOT
Principal Investigator Email
Chivot.Cyril@chu-amiens.fr
Contact Person Name
Cyril CHIVOT
Contact Person Email
Chivot.Cyril@chu-amiens.fr
Site Name
Bicetre Hospital
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Jildaz CAROFF
Principal Investigator Email
jildaz.caroff@gmail.com
Contact Person Name
Jildaz CAROFF
Contact Person Email
jildaz.caroff@gmail.com
Site Name
CHU De Rouen
Department Name
Neuroradiologie diagnostique et Interventionnelle
Principal Investigator Name
Chrisanthi PAPAGIANNAKI
Principal Investigator Email
c.papagiannaki@chu-rouen.fr
Contact Person Name
Chrisanthi PAPAGIANNAKI
Contact Person Email
c.papagiannaki@chu-rouen.fr
Site Name
Hospital Foch
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Arturo CONSOLI
Principal Investigator Email
a.consoli@hopital-foch.com
Contact Person Name
Arturo CONSOLI
Contact Person Email
a.consoli@hopital-foch.com
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Neuroradiologie
Principal Investigator Name
Olivier HECK
Principal Investigator Email
oheck@chu-grenoble.fr
Contact Person Name
Olivier HECK
Contact Person Email
oheck@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Neuroradiologie Interventionnelle et Diagnostique
Principal Investigator Name
Gaultier MARNAT
Principal Investigator Email
gaultier.marnat@chu-bordeaux.fr
Contact Person Name
Gaultier MARNAT
Site Name
Assistance Publique Hopitaux De Paris (site 2)
Department Name
Neuroradiologie
Principal Investigator Name
Marc-Antoine LABEYRIE
Principal Investigator Email
marc-antoine.labeyrie@aphp.fr
Contact Person Name
Marc-Antoine LABEYRIE
Contact Person Email
marc-antoine.labeyrie@aphp.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Radiologie
Principal Investigator Name
Charlotte BARBIER
Principal Investigator Email
barbier-ch@chu-caen.fr
Contact Person Name
Charlotte BARBIER
Contact Person Email
barbier-ch@chu-caen.fr
Site Name
Hopital Fondation Adolphe De Rothschild
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Jean-Philippe DESILLES
Principal Investigator Email
jpdesilles@for.paris
Contact Person Name
Jean-Philippe DESILLES
Contact Person Email
jpdesilles@for.paris
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
Radiologie
Principal Investigator Name
Jean-Christophe GENTRIC
Principal Investigator Email
jcgentric.nri.brest@chu-brest.fr
Contact Person Name
Jean-Christophe GENTRIC
Site Name
Centre Hospitalier Sainte Anne Paris
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Olivier NAGGARA
Principal Investigator Email
O.NAGGARA@ghu-paris.fr
Contact Person Name
Olivier NAGGARA
Contact Person Email
O.NAGGARA@ghu-paris.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Neurologie
Principal Investigator Name
Pacôme CONSTANT DIT BEAUFILS
Principal Investigator Email
pacome.constantditbeaufils@chu-nantes.fr
Contact Person Name
Pacôme CONSTANT DIT BEAUFILS
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Neuroradiologie diagnostique et Interventionnelle
Principal Investigator Name
Martin BRETZNER
Principal Investigator Email
martin.bretzner@chu-lille.fr
Contact Person Name
Martin BRETZNER
Contact Person Email
martin.bretzner@chu-lille.fr
Site Name
Centre Hospitalier De Pau
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Sebastian RICHTER
Principal Investigator Email
johannsebastian.richter@ch-pau.fr
Contact Person Name
Sebastian RICHTER
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Neuroradiologie Vasculaire Interventionnelle
Principal Investigator Name
Grégoire BOULOUIS
Principal Investigator Email
G.BOULOUIS@chu-tours.fr
Contact Person Name
Grégoire BOULOUIS
Contact Person Email
G.BOULOUIS@chu-tours.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Neuroradiologie et imagerie des urgences
Principal Investigator Name
Pierre-Olivier COMBY
Principal Investigator Email
pierre-olivier.comby@chu-dijon.fr
Contact Person Name
Pierre-Olivier COMBY
Site Name
CHRU De Nancy
Department Name
Neuroradiologie Diagnostique et Thérapeutique
Principal Investigator Name
Benjamin GORY
Principal Investigator Email
b.gory@chru-nancy.fr
Contact Person Name
Benjamin GORY
Contact Person Email
b.gory@chru-nancy.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Neuroradiologie Interventionnelle
Principal Investigator Name
Raoul POP
Principal Investigator Email
raoul.pop@chru-strasbourg.fr
Contact Person Name
Raoul POP
Contact Person Email
raoul.pop@chru-strasbourg.fr
Site Name
Centre Hospitalier Pasteur
Department Name
Radiodiagnostic et Imagerie Médicale
Principal Investigator Name
Pablo Ariel LEBEDINSKY
Principal Investigator Email
pablo.lebedinski@ch-colmar.fr
Contact Person Name
Pablo Ariel LEBEDINSKY
Contact Person Email
pablo.lebedinski@ch-colmar.fr

Sponsor

Primary sponsor

Full Name
CHRU De Nancy
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
ACTILYSE, poudre et solvant pour solution injectable et perfusion
Active Substance
Alteplase
Modality
Peptide/protein/enzyme
Routes Of Administration
Intra-arterial (INTRAARTERIAL USE)
Route
Intra-arterial
Authorisation Status
Marketing authorisation exists for IV indication (used intra-arterially in this trial, outside scope of MA)
Maximum Dose
20 mg

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