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

J 2019

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

ALEXANDROV, Andrei V., Georgios TSIVGOULIS, Martin KOHRMANN, Aristeidis H. KATSANOS, Lauri SOINNE et. al.

Basic information

Original name

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

Authors

ALEXANDROV, Andrei V. (840 United States of America), Georgios TSIVGOULIS (300 Greece), Martin KOHRMANN (276 Germany), Aristeidis H. KATSANOS (300 Greece), Lauri SOINNE (246 Finland), Andrew D. BARRETO (840 United States of America), Travis ROTHLISBERGER (840 United States of America), Vijay K. SHARMA (702 Singapore), Robert MIKULÍK (203 Czech Republic, belonging to the institution), Keith W. MUIR (826 United Kingdom of Great Britain and Northern Ireland), Christopher R. LEVI (36 Australia), Carlos A. MOLINA (724 Spain), Maher SAQQUR (124 Canada), Dimitris MAVRIDIS (300 Greece), Theodora PSALTOPOULOU (300 Greece), Milan R. VOSKO (40 Austria), Jochen B. FIEBACH (276 Germany), Pitchaiah MANDAVA (840 United States of America), Thomas A. KENT (840 United States of America), Anne W. ALEXANDROV (840 United States of America) and Peter D. SCHELLINGER (276 Germany)

Edition

THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS, LONDON, SAGE PUBLICATIONS LTD, 2019, 1756-2856

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.000

RIV identification code

RIV/00216224:14110/19:00110632

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1177/1756286419860652

UT WoS

000478614500001

Keywords in English

endovascular; equipoise shift; intracranial hemorrhage; mechanical thrombectomy; outcome; recanalization; sonothrombolysis; stroke; ultrasound-enhanced thrombolysis

Abstract

V originále

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.

Citovat

ALEXANDROV, Andrei V., Georgios TSIVGOULIS, Martin KOHRMANN, Aristeidis H. KATSANOS, Lauri SOINNE, Andrew D. BARRETO, Travis ROTHLISBERGER, Vijay K. SHARMA, Robert MIKULÍK, Keith W. MUIR, Christopher R. LEVI, Carlos A. MOLINA, Maher SAQQUR, Dimitris MAVRIDIS, Theodora PSALTOPOULOU, Milan R. VOSKO, Jochen B. FIEBACH, Pitchaiah MANDAVA, Thomas A. KENT, Anne W. ALEXANDROV and Peter D. SCHELLINGER. Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke. THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS. LONDON: SAGE PUBLICATIONS LTD, 2019, vol. 12, JUL 2019, p. 1-12. ISSN 1756-2856. Available from: https://dx.doi.org/10.1177/1756286419860652.

@article{1555139,
   author = {Alexandrov, Andrei V. and Tsivgoulis, Georgios and Kohrmann, Martin and Katsanos, Aristeidis H. and Soinne, Lauri and Barreto, Andrew D. and Rothlisberger, Travis and Sharma, Vijay K. and Mikulík, Robert and Muir, Keith W. and Levi, Christopher R. and Molina, Carlos A. and Saqqur, Maher and Mavridis, Dimitris and Psaltopoulou, Theodora and Vosko, Milan R. and Fiebach, Jochen B. and Mandava, Pitchaiah and Kent, Thomas A. and Alexandrov, Anne W. and Schellinger, Peter D.},
   article_location = {LONDON},
   article_number = {JUL 2019},
   doi = {http://dx.doi.org/10.1177/1756286419860652},
   keywords = {endovascular; equipoise shift; intracranial hemorrhage; mechanical thrombectomy; outcome; recanalization; sonothrombolysis; stroke; ultrasound-enhanced thrombolysis},
   language = {eng},
   issn = {1756-2856},
   journal = {THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS},
   title = {Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke},
   url = {http://dx.doi.org/10.1177/1756286419860652},
   volume = {12},
   year = {2019}
}

TY  - JOUR
ID  - 1555139
AU  - 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.
PY  - 2019
TI  - Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke
JF  - THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
VL  - 12
IS  - JUL 2019
SP  - 1-12
EP  - 1-12
PB  - SAGE PUBLICATIONS LTD
SN  - 17562856
KW  - endovascular
KW  - equipoise shift
KW  - intracranial hemorrhage
KW  - mechanical thrombectomy
KW  - outcome
KW  - recanalization
KW  - sonothrombolysis
KW  - stroke
KW  - ultrasound-enhanced thrombolysis
UR  - http://dx.doi.org/10.1177/1756286419860652
L2  - http://dx.doi.org/10.1177/1756286419860652
N2  - 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.
ER  -

ALEXANDROV, Andrei V., Georgios TSIVGOULIS, Martin KOHRMANN, Aristeidis H. KATSANOS, Lauri SOINNE, Andrew D. BARRETO, Travis ROTHLISBERGER, Vijay K. SHARMA, Robert MIKULÍK, Keith W. MUIR, Christopher R. LEVI, Carlos A. MOLINA, Maher SAQQUR, Dimitris MAVRIDIS, Theodora PSALTOPOULOU, Milan R. VOSKO, Jochen B. FIEBACH, Pitchaiah MANDAVA, Thomas A. KENT, Anne W. ALEXANDROV and Peter D. SCHELLINGER. Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke. \textit{THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS}. LONDON: SAGE PUBLICATIONS LTD, 2019, vol.~12, JUL 2019, p.~1-12. ISSN~1756-2856. Available from: https://dx.doi.org/10.1177/1756286419860652.

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