{
  "abstract": "Rationale The potential value of rescue intra-arterial thrombolysis in patients with large vessel occlusion (LVO) stroke treated with mechanical thrombectomy (MT) remains to be validated in randomised trials.Aim The Chemical Optimization of Cerebral Embolectomy 2 (CHOICE 2) trial is designed to confirm whether adjunctive intra-arterial alteplase, administered after successful MT, improves clinical outcomes in patients with LVO stroke.Sample size estimates A total of 440 patients (220 per group) randomised in a 1:1 ratio to receive intra-arterial thrombolysis or not intra-arterial thrombolysis provides 80% statistical power to detect a 14% absolute benefit in the primary endpoint (the proportion of patients achieving modified Rankin Scale (mRS) 0–1 at 90 days), assuming a rate of 40% in the control group, a 5% two-sided type I error. The sample size also provides >95% power for detecting an 18% absolute benefit in secondary imaging endpoints, assuming a 58% rate in the control group.Methods and design Multicentre, randomised, open, blinded end-point assessment phase III trial. Eligible patients are adults (≥18 years) with symptomatic LVO who undergo MT with successful or complete reperfusion at end of the procedure. Patients in the intervention group will receive a 15 min intra-arterial infusion of alteplase (1.0 mg/mL, maximum dose 20 mg).Study outcome(s) The primary outcome is the proportion of patients achieving excellent functional outcome (mRS 0–1) at 90 days. Key secondary outcomes are the presence of hypoperfusion on brain CT perfusion at 36±24 hours post randomisation, infarct expansion, Barthel Index and quality of life. Mortality and symptomatic intracerebral haemorrhage will also be evaluated.Discussion This trial will provide evidence whether rescue intra-arterial thrombolysis improves clinical outcome in patients with LVO stroke who achieve successful or complete angiographic reperfusion following MT.",
  "authors": [
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), August Pi i Sunyer Institute of Biomedical Research, Barcelona, Barcelona, Spain"
      ],
      "name": "Arturo Renú"
    },
    {
      "affiliations": [
        "Neurology, Donostia Ospitalea, San Sebastián, Basque Country, Spain"
      ],
      "name": "Patricia de la Riva"
    },
    {
      "affiliations": [
        "Neurology, Son Espases University Hospital, Palma Mallorca, Balearic Island, Spain"
      ],
      "name": "Raquel Delgado-Mederos"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain"
      ],
      "name": "Laura Dorado"
    },
    {
      "affiliations": [
        "Neurology, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain"
      ],
      "name": "Maria Dolores Fernandez-Couto"
    },
    {
      "affiliations": [
        "Complejo Hospitalario de Navarra, Pamplona, Navarre, Spain"
      ],
      "name": "Maria Herrera-Isasi"
    },
    {
      "affiliations": [
        "Neurology, Dr Balmis General University Hospital, Alicante, Valencian Community, Spain"
      ],
      "name": "Nicolás López Hernández"
    },
    {
      "affiliations": [
        "Neurology, Virgen de la Arrixaca University Hospital, El Palmar, Región de Murcia, Spain"
      ],
      "name": "Ana Morales"
    },
    {
      "affiliations": [
        "Interventional Neuroradiology, La Fe University and Polytechnic Hospital, Valencia, Spain"
      ],
      "name": "Lluis Morales-Caba"
    },
    {
      "affiliations": [
        "Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"
      ],
      "name": "Pol Camps‐Renom"
    },
    {
      "affiliations": [
        "Avania Europe—Barcelona, Barcelona, Spain"
      ],
      "name": "Alba Singla"
    },
    {
      "affiliations": [
        "Neurology, Hospital Universitari de Girona Doctor Josep Trueta Servei de Neurologia, Girona, Girona, Spain"
      ],
      "name": "Mikel Terceño"
    },
    {
      "affiliations": [
        "Radiology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain"
      ],
      "name": "Pedro Vega"
    },
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), August Pi i Sunyer Institute of Biomedical Research, Barcelona, Barcelona, Spain"
      ],
      "name": "Sergio Amaro"
    },
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Neurointerventional Department, Hospital Clinic de Barcelona Centre de Diagnostic Biomedic, Barcelona, Spain"
      ],
      "name": "Jordi Blasco"
    },
    {
      "affiliations": [
        "Magnetic Resonance Imaging Core Facility, August Pi i Sunyer Institute of Biomedical Research, Barcelona, Spain"
      ],
      "name": "Carlos Laredo"
    },
    {
      "affiliations": [
        "Neurology, University of Iowa Health Care, Iowa City, Iowa, USA"
      ],
      "name": "Enrique C Leira"
    },
    {
      "affiliations": [
        "Radiology, Hospital Clinic de Barcelona Centre de Diagnostic per la Imatge Clinic, Barcelona, Spain"
      ],
      "name": "Laura Oleaga"
    },
    {
      "affiliations": [
        "Neurology, Doctor Josep Trueta University Hospital of Girona, Girona, Spain"
      ],
      "name": "Joaquin Serena"
    },
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), August Pi i Sunyer Institute of Biomedical Research, Barcelona, Barcelona, Spain"
      ],
      "name": "Xabier Urra"
    },
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Neurointerventional Department, Hospital Clinic de Barcelona Centre de Diagnostic Biomedic, Barcelona, Spain"
      ],
      "name": "Mariano Werner"
    },
    {
      "affiliations": [
        "Neurology, Complejo Hospitalario Universitario de Albacete, Albacete, Castilla-La Mancha, Spain"
      ],
      "name": "Francisco Hernández Fernández"
    },
    {
      "affiliations": [
        "Biostatistics and Epidemiology Unit, Autonomous University of Barcelona, Barcelona, Spain"
      ],
      "name": "Joan Valls"
    },
    {
      "affiliations": [
        "Neurology, Hospital Clinico Universitario de Valladolid, Valladolid, Spain"
      ],
      "name": "Juan Francisco Arenillas Lara"
    },
    {
      "affiliations": [
        "Neurology, Cruces University Hospital, Barakaldo, Basque Country, Spain"
      ],
      "name": "Maria del Mar Freijo"
    },
    {
      "affiliations": [
        "Neurology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain"
      ],
      "name": "Natalia Pérez de la Ossa"
    },
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Neurointerventional Department, Hospital Clinic de Barcelona Centre de Diagnostic Biomedic, Barcelona, Spain"
      ],
      "name": "Luis San Roman"
    },
    {
      "affiliations": [
        "Medical Statistics Core Facility, Clinical Pharmacology Service, Institut d’Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain",
        "Biostatistics Unit, Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain"
      ],
      "name": "Ferran Torres"
    },
    {
      "affiliations": [
        "Neurology, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain"
      ],
      "name": "Mar Castellanos"
    },
    {
      "affiliations": [
        "Neuroscience, Autonomous University of Barcelona, Barcelona, Spain"
      ],
      "name": "Antonio Davalos"
    },
    {
      "affiliations": [
        "Comprehensive Stroke Center, Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain",
        "Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), August Pi i Sunyer Institute of Biomedical Research, Barcelona, Barcelona, Spain"
      ],
      "name": "Angel Chamorro"
    },
    {
      "affiliations": [],
      "name": "CHOICE 2 Investigators"
    }
  ],
  "title": "Chemical Optimization of Cerebral Embolectomy 2 (CHOICE 2) trial: study protocol",
  "uid": "047ba3a7-c307-5942-a30d-71309bd96e11"
}