Publication details

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

Authors	ALEXANDROV Andrei V. TSIVGOULIS Georgios KOHRMANN Martin KATSANOS Aristeidis H. SOINNE Lauri BARRETO Andrew D. ROTHLISBERGER Travis SHARMA Vijay K. MIKULÍK Robert MUIR Keith W. LEVI Christopher R. MOLINA Carlos A. SAQQUR Maher MAVRIDIS Dimitris PSALTOPOULOU Theodora VOSKO Milan R. FIEBACH Jochen B. MANDAVA Pitchaiah KENT Thomas A. ALEXANDROV Anne W. SCHELLINGER Peter D.
Year of publication	2019
Type	Article in Periodical
Magazine / Source	THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
MU Faculty or unit	Faculty of Medicine
Citation
Web	http://dx.doi.org/10.1177/1756286419860652
Doi	http://dx.doi.org/10.1177/1756286419860652
Keywords	endovascular; equipoise shift; intracranial hemorrhage; mechanical thrombectomy; outcome; recanalization; sonothrombolysis; stroke; ultrasound-enhanced thrombolysis
Description	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.