Safety and efficacy of sonothrombolysis for acute ischaemic
stroke: a multicentre, double-blind, phase 3, randomised
controlled trial

J 2019

Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial

ALEXANDROV, Andrei, V., Martin KOHRMANN, Lauri SOINNE, Georgios TSIVGOULIS, Andrew D. BARRETO et. al.

Základní údaje

Originální název

Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial

Autoři

ALEXANDROV, Andrei, V. (840 Spojené státy, garant), Martin KOHRMANN (276 Německo), Lauri SOINNE (246 Finsko), Georgios TSIVGOULIS (300 Řecko), Andrew D. BARRETO (840 Spojené státy), Andrew M. DEMCHUK (124 Kanada), Vijay K. SHARMA (702 Singapur), Robert MIKULÍK (203 Česká republika, domácí), Keith W. MUIR (826 Velká Británie a Severní Irsko), Gordon BRANDT (840 Spojené státy), John ALLEMAN (840 Spojené státy), James C. GROTTA (840 Spojené státy), Christopher R. LEVI (36 Austrálie), Carlos A. MOLINA (724 Španělsko), Maher SAQQUR (124 Kanada), Dimitris MAVRIDIS (300 Řecko), Theodora PSALTOPOULOU (300 Řecko), Milan VOSKO (40 Rakousko), Jochen B. FIEBACH (276 Německo), Pitchaiah MANDAVA (840 Spojené státy), Thomas A. KENT (840 Spojené státy), Anne W. ALEXANDROV (840 Spojené státy) a Peter D. SCHELLINGER (276 Německo)

Vydání

Lancet Neurology, London, UK, Elsevier, 2019, 1474-4422

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30103 Neurosciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 30.039

Kód RIV

RIV/00216224:14110/19:00112519

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/S1474-4422(19)30026-2

UT WoS

000461169400011

Klíčová slova anglicky

ULTRASOUND-ENHANCED THROMBOLYSIS; TISSUE-PLASMINOGEN ACTIVATOR; ALTEPLASE; DEVICE

Štítky

14110127, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 1. 2020 15:13, Mgr. Tereza Miškechová

Anotace

V originále

Background Pulsed-wave ultrasound increases the exposure of an intracranial thrombus to alteplase (recombinant tissue plasminogen activator), potentially facilitating early reperfusion. We aimed to ascertain if a novel operator-independent transcranial ultrasound device delivering low-power high-frequency ultrasound could improve functional outcome in patients treated with alteplase after acute ischaemic stroke. Methods We did a multicentre, double-blind, phase 3, randomised controlled trial (CLOTBUST-ER) at 76 medical centres in 14 countries. We included patients with acute ischaemic stroke (National Institutes of Health Stroke Scale score >= 10) who received intravenous thrombolysis (alteplase bolus) within 3 h of symptom onset in North America and within 4.5 h of symptom onset in all other countries. Participants were randomly allocated (1:1) via an interactive web response system to either active ultrasound (2 MHz pulsed-wave ultrasound for 120 min [sonothrombolysis]; intervention group) or sham ultrasound (control group). Ultrasound was delivered using an operator-independent device, which had to be activated within 30 min of the alteplase bolus. Participants, investigators, and those assessing outcomes were unaware of group assignments. The primary outcome was improvement in the modified Rankin Scale score at 90 days in patients enrolled within 3 h of symptom onset, assessed in the intention-to-treat population as a common odds ratio (cOR) using ordinal logistic regression shift analysis. This trial is registered with ClinicalTrials.gov , number NCT01098981. The trial was stopped early by the funder after the second interim analysis because of futility. Findings Between August, 2013, and April, 2015, 335 patients were randomly allocated to the intervention group and 341 patients to the control group. Compared with the control group, the adjusted cOR for an improvement in modified Rankin Scale score at 90 days in the intervention group was 1.05 (95% CI 0.77-1.45; p=0.74). 51 (16%) of 317 patients in the intervention group and 44 (13%) of 329 patients in the control group died (unadjusted OR 1.24, 95% CI 0 .80-1. 92; 13=0.37) and 83 (26%) and 79 (24%), respectively, had serious adverse events (1.12, 0.79-1.60; p=0.53). Interpretation Sonothrombolysis delivered by an operator-independent device to patients treated with alteplase after acute ischaemic stroke was feasible and most likely safe, but no clinical benefit was seen at 90 days. Sonothrombolysis could be further investigated either in randomised trials undertaken in stroke centres that are dependent on patient transfer for endovascular reperfusion therapies or in countries where these treatments cannot yet be offered as the standard of care. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Citovat

ALEXANDROV, Andrei, V., Martin KOHRMANN, Lauri SOINNE, Georgios TSIVGOULIS, Andrew D. BARRETO, Andrew M. DEMCHUK, Vijay K. SHARMA, Robert MIKULÍK, Keith W. MUIR, Gordon BRANDT, John ALLEMAN, James C. GROTTA, Christopher R. LEVI, Carlos A. MOLINA, Maher SAQQUR, Dimitris MAVRIDIS, Theodora PSALTOPOULOU, Milan VOSKO, Jochen B. FIEBACH, Pitchaiah MANDAVA, Thomas A. KENT, Anne W. ALEXANDROV a Peter D. SCHELLINGER. Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Neurology. London, UK: Elsevier, 2019, roč. 18, č. 4, s. 338-347. ISSN 1474-4422. Dostupné z: https://dx.doi.org/10.1016/S1474-4422(19)30026-2.

@article{1605637,
   author = {Alexandrov, Andrei, V. and Kohrmann, Martin and Soinne, Lauri and Tsivgoulis, Georgios and Barreto, Andrew D. and Demchuk, Andrew M. and Sharma, Vijay K. and Mikulík, Robert and Muir, Keith W. and Brandt, Gordon and Alleman, John and Grotta, James C. and Levi, Christopher R. and Molina, Carlos A. and Saqqur, Maher and Mavridis, Dimitris and Psaltopoulou, Theodora and Vosko, Milan and Fiebach, Jochen B. and Mandava, Pitchaiah and Kent, Thomas A. and Alexandrov, Anne W. and Schellinger, Peter D.},
   article_location = {London, UK},
   article_number = {4},
   doi = {http://dx.doi.org/10.1016/S1474-4422(19)30026-2},
   keywords = {ULTRASOUND-ENHANCED THROMBOLYSIS; TISSUE-PLASMINOGEN ACTIVATOR; ALTEPLASE; DEVICE},
   language = {eng},
   issn = {1474-4422},
   journal = {Lancet Neurology},
   title = {Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial},
   url = {http://dx.doi.org/10.1016/S1474-4422(19)30026-2},
   volume = {18},
   year = {2019}
}

TY  - JOUR
ID  - 1605637
AU  - Alexandrov, Andrei, V. - Kohrmann, Martin - Soinne, Lauri - Tsivgoulis, Georgios - Barreto, Andrew D. - Demchuk, Andrew M. - Sharma, Vijay K. - Mikulík, Robert - Muir, Keith W. - Brandt, Gordon - Alleman, John - Grotta, James C. - Levi, Christopher R. - Molina, Carlos A. - Saqqur, Maher - Mavridis, Dimitris - Psaltopoulou, Theodora - Vosko, Milan - Fiebach, Jochen B. - Mandava, Pitchaiah - Kent, Thomas A. - Alexandrov, Anne W. - Schellinger, Peter D.
PY  - 2019
TI  - Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial
JF  - Lancet Neurology
VL  - 18
IS  - 4
SP  - 338-347
EP  - 338-347
PB  - Elsevier
SN  - 14744422
KW  - ULTRASOUND-ENHANCED THROMBOLYSIS
KW  - TISSUE-PLASMINOGEN ACTIVATOR
KW  - ALTEPLASE
KW  - DEVICE
UR  - http://dx.doi.org/10.1016/S1474-4422(19)30026-2
L2  - http://dx.doi.org/10.1016/S1474-4422(19)30026-2
N2  - Background Pulsed-wave ultrasound increases the exposure of an intracranial thrombus to alteplase (recombinant tissue plasminogen activator), potentially facilitating early reperfusion. We aimed to ascertain if a novel operator-independent transcranial ultrasound device delivering low-power high-frequency ultrasound could improve functional outcome in patients treated with alteplase after acute ischaemic stroke. Methods We did a multicentre, double-blind, phase 3, randomised controlled trial (CLOTBUST-ER) at 76 medical centres in 14 countries. We included patients with acute ischaemic stroke (National Institutes of Health Stroke Scale score >= 10) who received intravenous thrombolysis (alteplase bolus) within 3 h of symptom onset in North America and within 4.5 h of symptom onset in all other countries. Participants were randomly allocated (1:1) via an interactive web response system to either active ultrasound (2 MHz pulsed-wave ultrasound for 120 min [sonothrombolysis]; intervention group) or sham ultrasound (control group). Ultrasound was delivered using an operator-independent device, which had to be activated within 30 min of the alteplase bolus. Participants, investigators, and those assessing outcomes were unaware of group assignments. The primary outcome was improvement in the modified Rankin Scale score at 90 days in patients enrolled within 3 h of symptom onset, assessed in the intention-to-treat population as a common odds ratio (cOR) using ordinal logistic regression shift analysis. This trial is registered with ClinicalTrials.gov , number NCT01098981. The trial was stopped early by the funder after the second interim analysis because of futility. Findings Between August, 2013, and April, 2015, 335 patients were randomly allocated to the intervention group and 341 patients to the control group. Compared with the control group, the adjusted cOR for an improvement in modified Rankin Scale score at 90 days in the intervention group was 1.05 (95% CI 0.77-1.45; p=0.74). 51 (16%) of 317 patients in the intervention group and 44 (13%) of 329 patients in the control group died (unadjusted OR 1.24, 95% CI 0 .80-1. 92; 13=0.37) and 83 (26%) and 79 (24%), respectively, had serious adverse events (1.12, 0.79-1.60; p=0.53). Interpretation Sonothrombolysis delivered by an operator-independent device to patients treated with alteplase after acute ischaemic stroke was feasible and most likely safe, but no clinical benefit was seen at 90 days. Sonothrombolysis could be further investigated either in randomised trials undertaken in stroke centres that are dependent on patient transfer for endovascular reperfusion therapies or in countries where these treatments cannot yet be offered as the standard of care. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
ER  -

ALEXANDROV, Andrei, V., Martin KOHRMANN, Lauri SOINNE, Georgios TSIVGOULIS, Andrew D. BARRETO, Andrew M. DEMCHUK, Vijay K. SHARMA, Robert MIKULÍK, Keith W. MUIR, Gordon BRANDT, John ALLEMAN, James C. GROTTA, Christopher R. LEVI, Carlos A. MOLINA, Maher SAQQUR, Dimitris MAVRIDIS, Theodora PSALTOPOULOU, Milan VOSKO, Jochen B. FIEBACH, Pitchaiah MANDAVA, Thomas A. KENT, Anne W. ALEXANDROV a Peter D. SCHELLINGER. Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial. \textit{Lancet Neurology}. London, UK: Elsevier, 2019, roč.~18, č.~4, s.~338-347. ISSN~1474-4422. Dostupné z: https://dx.doi.org/10.1016/S1474-4422(19)30026-2.

Podrobný výpis o publikaci