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

Alexandrov AV, Tsivgoulis G, Köhrmann M, Katsanos AH, Soinne L, Barreto AD, Rothlisberger T, Sharma VK, Mikulik R, Muir KW, Levi CR, Molina CA, Saqqur M, Mavridis D, Psaltopoulou T, Vosko MR, Fiebach JB, Mandava P, Kent TA, Alexandrov AW, Schellinger PD (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 12

DOI: 10.1177/1756286419860652

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.

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Additional Organisation(s)

Involved external institutions

Helsingin yliopisto / University of Helsinki Finland (FI) University Hospital Brno Czech Republic (CZ) National University of Singapore (NUS) Singapore (SG) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) Ruhr-Universität Bochum (RUB) Germany (DE) The University of Tennessee Health Science Center United States (USA) (US) National and Kapodistrian University of Athens Greece (GR) Johannes Kepler Universität (JKU) Linz Austria (AT) Baylor College of Medicine United States (USA) (US) University of Glasgow United Kingdom (GB) Cerevast Medical, Inc. United States (USA) (US) Charité - Universitätsmedizin Berlin Germany (DE) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Attikon Hospital / Πανεπιστημιακού Γενικού Νοσοκομείου "Αττικόν" Greece (GR) University of Alberta Canada (CA) University of Ioannina / Πανεπιστήμιο Ιωαννίνων Greece (GR) University of Newcastle (UoN) Australia (AU)

How to cite

APA:

Alexandrov, A.V., Tsivgoulis, G., Köhrmann, M., Katsanos, A.H., Soinne, L., Barreto, A.D.,... Schellinger, P.D. (2019). Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke. Therapeutic Advances in Neurological Disorders, 12. https://dx.doi.org/10.1177/1756286419860652

MLA:

Alexandrov, Andrei V., et al. "Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke." Therapeutic Advances in Neurological Disorders 12 (2019).

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