Academic Journal
Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment
| العنوان: | Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment |
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| المؤلفون: | Hernández-Jiménez, Macarena, Abad-Santos, Francisco, Cotgreave, Ian, Gallego, Jaime, Jilma, Bernd, Flores, Alan, Jovin, Tudor, Vivancos, José, Hernández-Pérez, María, Molina, Carlos, Montaner, Joan, Casariego, Joaquín, Dalsgaard, Mads, Liebeskind, David, Cobo, Erik, Castellanos, Mar, Portela, Pere Cardona, Masjuán, Jaime, Moniche, Francisco, Tembl, José Ignacio, Terceño Izaga, Mikel, Arenillas, Juan, Calleja, Patricia, Olivot, Jean Marc, Calviere, Lionel, Henon, Hilde, Mazighi, Mikael, Piñeiro, David, Pugliese, Marco, González, Victor, Moro, Maria Angeles, Garcia-Tornel, Alvaro, Lizasoain, Ignacio, Ribo, Marc |
| المساهمون: | aptaTargets, Instituto de Salud Carlos III Madrid (ISC), Hospital Universitario de La Princesa, RISE Research Institutes of Sweden, Neurological Center of Navarra = Centro Neurologico de Navarra, Medizinische Universität Wien = Medical University of Vienna, Hospital Universitari Joan XXIII = University hospital Joan XXIII, Cooper University Health Care, Germans Trias i Pujol University Hospital Badalona, Barcelona, Spain (GTPUH), Vall d'Hebron University Hospital Barcelona, Toulouse NeuroImaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT) |
| المصدر: | ISSN: 2168-6149. |
| بيانات النشر: | HAL CCSD American Medical Association |
| سنة النشر: | 2023 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | MESH: Brain Ischemia / complications, MESH: Brain Ischemia / diagnostic imaging, MESH: Ischemic Stroke / surgery, MESH: Male, MESH: Stroke / diagnostic imaging, MESH: Stroke / drug therapy, MESH: Thrombectomy / methods, MESH: Treatment Outcome, MESH: Brain Ischemia / drug therapy, MESH: Cerebral Infarction / complications, MESH: Endovascular Procedures / methods, MESH: Female, MESH: Humans, MESH: Intracranial Hemorrhages / etiology, MESH: Ischemic Stroke / diagnostic imaging, MESH: Ischemic Stroke / drug therapy, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Importance ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37338893; PUBMED: 37338893; PUBMEDCENTRAL: PMC10282959 |
| DOI: | 10.1001/jamaneurol.2023.1660 |
| الاتاحة: | https://hal.science/hal-04702048 https://doi.org/10.1001/jamaneurol.2023.1660 |
| رقم الانضمام: | edsbas.699175E4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1001/jamaneurol.2023.1660 |
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