Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients with Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial

Arturo Renú, Mónica Millán, Luis San Román, Jordi Blasco, Joan Martí-Fàbregas, Mikel Terceño, Sergio Amaro, Joaquín Serena, Xabier Urra, Carlos Laredo, Roger Barranco, Pol Camps-Renom, Federico Zarco, Laura Oleaga, Pere Cardona, Carlos Castaño, Juan Macho, Elisa Cuadrado-Godía, Elio Vivas, Antonio López-RuedaLeopoldo Guimaraens, Anna Ramos-Pachón, Jaume Roquer, Marian Muchada, Alejandro Tomasello, Antonio Dávalos, Ferran Torres, Ángel Chamorro*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1645
Pages (from-to)826-835
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume327
Issue number9
DOIs
Publication statusPublished - 1 Mar 2022

Keywords

  • BENEFIT
  • ENDOVASCULAR THROMBECTOMY
  • HEALTH
  • MANAGEMENT
  • MECHANICAL CLOT DISRUPTION
  • THERAPY

Fingerprint

Dive into the research topics of 'Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients with Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial'. Together they form a unique fingerprint.

Cite this