TY - JOUR
T1 - Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients with Large Vessel Occlusion Acute Ischemic Stroke
T2 - The CHOICE Randomized Clinical Trial
AU - Renú, Arturo
AU - Millán, Mónica
AU - San Román, Luis
AU - Blasco, Jordi
AU - Martí-Fàbregas, Joan
AU - Terceño, Mikel
AU - Amaro, Sergio
AU - Serena, Joaquín
AU - Urra, Xabier
AU - Laredo, Carlos
AU - Barranco, Roger
AU - Camps-Renom, Pol
AU - Zarco, Federico
AU - Oleaga, Laura
AU - Cardona, Pere
AU - Castaño, Carlos
AU - Macho, Juan
AU - Cuadrado-Godía, Elisa
AU - Vivas, Elio
AU - López-Rueda, Antonio
AU - Guimaraens, Leopoldo
AU - Ramos-Pachón, Anna
AU - Roquer, Jaume
AU - Muchada, Marian
AU - Tomasello, Alejandro
AU - Dávalos, Antonio
AU - Torres, Ferran
AU - Chamorro, Ángel
AU - Ríos, J
N1 - Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - IMPORTANCE It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits.OBJECTIVE To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion.DESIGN, SETTING, AND PARTICIPANTS Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral lschemia angiographic score of 2b50 to 3.INTERVENTIONS Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52).MAIN OUTCOMES AND MEASURES The primary outcome was the difference in proportion of patients achieving a score of 0 or ion the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death.RESULTS The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121(7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference. 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%).CONCLUSIONS AND RELEVANCE Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication.
AB - IMPORTANCE It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits.OBJECTIVE To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion.DESIGN, SETTING, AND PARTICIPANTS Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral lschemia angiographic score of 2b50 to 3.INTERVENTIONS Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52).MAIN OUTCOMES AND MEASURES The primary outcome was the difference in proportion of patients achieving a score of 0 or ion the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death.RESULTS The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121(7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference. 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%).CONCLUSIONS AND RELEVANCE Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication.
KW - BENEFIT
KW - ENDOVASCULAR THROMBECTOMY
KW - HEALTH
KW - MANAGEMENT
KW - MECHANICAL CLOT DISRUPTION
KW - THERAPY
UR - http://www.scopus.com/inward/record.url?scp=85124901288&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/6bfad08e-c4a0-31fa-92f1-78a0a22bcf91/
U2 - 10.1001/jama.2022.1645
DO - 10.1001/jama.2022.1645
M3 - Article
C2 - 35143603
AN - SCOPUS:85124901288
SN - 0098-7484
VL - 327
SP - 826
EP - 835
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 9
M1 - 1645
ER -