Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke. Academic Article uri icon


  • 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.

published proceedings

  • Ther Adv Neurol Disord

altmetric score

  • 3

author list (cited authors)

  • Alexandrov, A. V., Tsivgoulis, G., Khrmann, M., Katsanos, A. H., Soinne, L., Barreto, A. D., ... CLOTBUST-ER Trial Investigators.

citation count

  • 7

complete list of authors

  • Alexandrov, Andrei V||Tsivgoulis, Georgios||K√∂hrmann, Martin||Katsanos, Aristeidis H||Soinne, Lauri||Barreto, Andrew D||Rothlisberger, Travis||Sharma, Vijay K||Mikulik, 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

publication date

  • January 2019