Arturo Renú, María Dolores Fernández-Couto, Patricia De La Riva, Raquel Delgado‐Mederos, María Herrera, A MORALES, Mikel Terceño, Nicolás López-Hernández, Mario Martínez-Galdámez, Laura Dorado, Pedro Vega, Lluís Morales‐Caba, Eva González, Maitane Alonso, Pedro Barredo Benitez, Rebeca Bermejo, Andrea Cabero-Arnold, José María Cabrera‐Maqueda, Martha Vargas, Angel Calleja Bonilla, Sergio Calleja, José Díaz‐Pérez, Salvatore Rudilosso, Antonio Doncel-Moriano, María José Feal, José Ignacio Gallego, Paola Hurtado, Carlos Laredo, Laura Llull, Inés Bartolomé, Alberto Martínez‐Calvo, Álvaro Ortega-Sánchez, Alejandro Rodríguez-Vázquez, Isabel Rodríguez‐Caamaño, Alba Singla, Yolanda Silva, Diana Tarruella Hernández, Laura Oleaga, Luis San Román Manzanera, Joaquı́n Serena, María Mar Freijo, Natalia Pérez de la Ossa, Mar Castellanos, Juan Francisco Arenillas-Lara, Ferran Torres, Enrique C. Leira, Sergio Amaro, Xabier Urra, Ángel Chamorro, CHOICE-2 Investigators, Mar Guasp, Guillem Dolz, Jordi Sarto, Mariano Werner, Diana Esteller, Mònica Serrano, Almudena Sánchez, Sergio Borrego, Gerard Mayà, Aída Alejaldre, Marta Olivera, Jordi Blasco, Juan Macho, Andrés Girona, Miquel Massons, Victor Guerra, Albert Mas, Carla Brenlla, Ona Brengaret, Irene Rosa, Darío Ramis, Daniel Asin, David Moraleja, Nouha Bennouna, Berta Jove, Joan Tutusaus, Marina Ruiz, Francisco Javier Reyes, Beatriz Gomez, Mercedes C. de Lera, Ana Calleja, Alicia Sierra, Gonzalo Valle, Elisa Cortijo, Maria Esther Ramos, Lorenzo Ismael Pérez, Miguel Schüller, Jorge Galván, E. Burón Martínez, Alba Chavarría, Carmen Montero, Paula Viñuales, Javier Manso Del Caño, Ion Labayen, Jon Fondevila, Alain Luna, C. Suárez Fernández, Jon Martin, Iratxe Ugarriza, Tomás Pérez
Importance: Despite high recanalization rates with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion, functional outcomes remain suboptimal. The benefit of adjunctive intra-arterial thrombolysis after successful thrombectomy is uncertain. Objective: To assess whether adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion. Design, Setting, and Participants: Randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain from December 11, 2023, through November 26, 2025. A total of 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 were randomized. Interventions: Thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg) infused over 15 minutes (n = 221) or thrombectomy alone (n = 219). Main Outcomes and Measures: The primary outcome was an excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0 or 1. There were 6 secondary outcomes, including residual hypoperfusion on follow-up computed tomography perfusion. The safety outcomes included symptomatic intracranial hemorrhage and death. Results: Of 3786 patients treated with thrombectomy, 2776 (73%) fulfilled angiographic criteria and 440 (12%) were randomized. There were 433 patients who were treated as randomized (median age, 76 [IQR, 75-78] years; 51% female). At 90 days, 57.5% of patients (123/214) in the thrombectomy plus intra-arterial alteplase group had a modified Rankin Scale score of 0 or 1 vs 42.5% of patients (93/219) in the thrombectomy alone group (adjusted risk difference, 15.0% [95% CI, 5.7% to 24.3%]; P = .002). Of 6 secondary outcomes, 4 showed no significant between-group differences. Residual hypoperfusion occurred in 28.6% (55/192) of patients in the thrombectomy plus intra-arterial alteplase group vs 50.5% (96/190) of patients in the thrombectomy alone group (adjusted risk difference, -22.0% [95% CI, -31.5% to -12.4%]; P < .001) and symptomatic intracranial hemorrhage occurred in 1.4% (3/214) vs 0.5% (1/219), respectively (adjusted odds ratio, 3.10 [95% CI, 0.32 to 30.0]; P = .33). Mortality at 90 days was 12.1% (26/214) in the thrombectomy plus intra-arterial alteplase group vs 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9% [95% CI, 0.5% to 11.3%]; P = .03). Conclusions and Relevance: Among patients with acute ischemic stroke and successful thrombectomy, adjunctive intra-arterial alteplase increased the proportion achieving excellent functional outcome at 90 days without a significant increase in symptomatic intracranial hemorrhage. Higher mortality in the thrombectomy plus intra-arterial alteplase group warrants further study. Trial Registration: ClinicalTrials.gov Identifier: NCT05797792.