Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke

Alexandrov, A. V. et al. (2019) Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke. Therapeutic Advances in Neurological Disorders, 12, (doi: 10.1177/1756286419860652) (PMID:31320933) (PMCID:PMC6628520)

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Abstract

Background: Results of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers. Methods: We performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials. Results: From a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p < 0.01) interaction of perceived endovascular equipoise shift on the association between sonothrombolysis and 3 month functional outcome [adjusted common odds ratio (cOR) in centers with perceived endovascular equipoise shift: 0.22, 95% CI 0.06–0.75; p = 0.02; adjusted cOR for centers without endovascular equipoise shift: 1.20, 95% CI 0.89–1.62; p = 0.24)]. After excluding centers with perceived endovascular equipoise shift, patients randomized to sonothrombolysis had higher odds of 3 month functional independence (mRS scores 0–2) compared with patients treated with tPA only (adjusted OR: 1.53; 95% CI 1.01–2.31; p = 0.04). Conclusion: Our experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies.

Item Type:Articles
Additional Information:The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: RM has been supported by the National Program of Sustainability II (MEYS CR; project number LQ1605) and by FNUSAICRC (project number CZ.1.05/1.1.00/02.0123; OP VaVpI); AHK has been supported by a Research Experience Fellowship from the European Academy of Neurology.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Muir, Professor Keith
Authors: Alexandrov, A. V., Tsivgoulis, G., Köhrmann, M., Katsanos, A. H., Soinne, L., Barreto, A. D., Rothlisberger, T., Sharma, V. K., Mikulik, R., Muir, K. W., Levi, C. R., Molina, C. A., Saqqur, M., Mavridis, D., Psaltopoulou, T., Vosko, M. R., Fiebach, J. B., Mandava, P., Kent, T. A., Alexandrov, A. W., and Schellinger, P. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Therapeutic Advances in Neurological Disorders
Publisher:SAGE Publications
ISSN:1756-2856
ISSN (Online):1756-2864
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Therapeutic Advances in Neurological Disorders 12
Publisher Policy:Reproduced under a Creative Commons license

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