A Pilot Randomized Clinical Safety Study of Sonothrombolysis
Augmentation With Ultrasound Activated Perflutren Lipid
Microspheres for Acute Ischemic Stroke

J 2008

A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke

ALEXANDROV, Andrei, Robert MIKULÍK, Marc RIBO, Vijay SHARMA, Annabelle LAO et. al.

Basic information

Original name

A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke

Name in Czech

Pilotni randomizovana studie na bezpecnost sonotrombolyzou aktivovanych perflutrenovych mikrosfer u pacientu s akutnim mozkovym infarktem

Authors

ALEXANDROV, Andrei (840 United States of America), Robert MIKULÍK (203 Czech Republic, guarantor, belonging to the institution), Marc RIBO (724 Spain), Vijay SHARMA (702 Singapore), Annabelle LAO (840 United States of America), Georgious TSIVGOULIS (300 Greece), Rebecca SUGG (840 United States of America), Andrew BARETTO (840 United States of America), Paul SIERZENSKI (840 United States of America), Marc MALKOFF (840 United States of America) and James GROTTA (840 United States of America)

Edition

Stroke : a journal of cerebral circulation, Dallas, American Heart Association, 2008, 0039-2499

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 6.499

RIV identification code

RIV/00216224:14110/08:00050977

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1161/STROKEAHA.107.505727

UT WoS

000255393100012

Keywords in English

microspheres; thrombolysis; stroke; occlusion; transcranial Doppler

Abstract

ORIG CZ

V originále

Background and Purpose: Ultrasound transiently expands perflutren lipid microspheres (microspheres), transmitting energy momentum to surrounding fluids. We report a pilot safety/feasibility study of ultrasound-activated microspheres with systemic tissue plasminogen activator (tPA). Methods: Stroke subjects treated within 3 hours had abnormal Thrombolysis in Brain Ischemia (TIBI) residual flow grades 0 to 3 before tPA on transcranial Doppler (TCD). Randomization included Controls (tPA plus TCD) or Target (tPA plus TCD plus 2.8 mL microspheres). The primary safety end point was symptomatic intracranial hemorrhage (sICH) with worsening by 4 or more NIHSS points within 72 hours. Results: Fifteen subjects were randomized 3:1 to Target, n=12 or Control, n=3. After treatment, asymptomatic ICH occurred in 3 Target and 1 Control, and sICH was not seen in any study subject. Microspheres reached MCA occlusions in all Target subjects at velocities higher than surrounding residual red blood cell flow: 39.8 plus minus 11.3 vs 28.8 plus minus 13.8 cm/s,P=0.001. In 75% of subjects, microspheres permeated to areas with no pretreatment residual flow, and in 83% residual flow velocity improved at a median of 30 minutes from start of microspheres infusion (range 30 s to 120 minutes) by a median of 17 cm/s (118% above pretreatment values). To provide perspective, current study recanalization rates were compared with the tPA control arm of the CLOTBUST trial: complete recanalization 50% versus 18%, partial 33% versus 33%, none 17% versus 49%, P=0.028. At 2 hours, sustained complete recanalization was 42% versus 13%, P=0.003, and NIHSS scores 0 to 3 were reached by 17% versus 8%, P=0.456. Conclusions: Perflutren microspheres reached and permeated beyond intracranial occlusions with no increase in sICH after systemic thrombolysis suggesting feasibility of further microspheres dose escalation studies and development of drug delivery to tissues with compromised perfusion.

In Czech

Tato pilotni randomizovana studie prokazala bezpecnost sonotrombolyzou aktivovanych perflutrenovych mikrosfer u pacientu s akutnim mozkovym infarktem

Citovat

ALEXANDROV, Andrei, Robert MIKULÍK, Marc RIBO, Vijay SHARMA, Annabelle LAO, Georgious TSIVGOULIS, Rebecca SUGG, Andrew BARETTO, Paul SIERZENSKI, Marc MALKOFF and James GROTTA. A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke. Stroke : a journal of cerebral circulation. Dallas: American Heart Association, 2008, vol. 39, No 5, p. 1464-1469. ISSN 0039-2499. Available from: https://dx.doi.org/10.1161/STROKEAHA.107.505727.

@article{768463,
   author = {Alexandrov, Andrei and Mikulík, Robert and Ribo, Marc and Sharma, Vijay and Lao, Annabelle and Tsivgoulis, Georgious and Sugg, Rebecca and Baretto, Andrew and Sierzenski, Paul and Malkoff, Marc and Grotta, James},
   article_location = {Dallas},
   article_number = {5},
   doi = {http://dx.doi.org/10.1161/STROKEAHA.107.505727},
   keywords = {microspheres; thrombolysis; stroke; occlusion; transcranial Doppler},
   language = {eng},
   issn = {0039-2499},
   journal = {Stroke : a journal of cerebral circulation},
   title = {A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke},
   volume = {39},
   year = {2008}
}

TY  - JOUR
ID  - 768463
AU  - Alexandrov, Andrei - Mikulík, Robert - Ribo, Marc - Sharma, Vijay - Lao, Annabelle - Tsivgoulis, Georgious - Sugg, Rebecca - Baretto, Andrew - Sierzenski, Paul - Malkoff, Marc - Grotta, James
PY  - 2008
TI  - A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke
JF  - Stroke : a journal of cerebral circulation
VL  - 39
IS  - 5
SP  - 1464-1469
EP  - 1464-1469
PB  - American Heart Association
SN  - 00392499
KW  - microspheres
KW  - thrombolysis
KW  - stroke
KW  - occlusion
KW  - transcranial Doppler
N2  - Background and Purpose: Ultrasound transiently expands perflutren lipid microspheres (microspheres), transmitting energy momentum to surrounding fluids. We report a pilot safety/feasibility study of ultrasound-activated microspheres with systemic tissue plasminogen activator (tPA). Methods: Stroke subjects treated within 3 hours had abnormal Thrombolysis in Brain Ischemia (TIBI) residual flow grades 0 to 3 before tPA on transcranial Doppler (TCD). Randomization included Controls (tPA plus TCD) or Target (tPA plus TCD plus 2.8 mL microspheres). The primary safety end point was symptomatic intracranial hemorrhage (sICH) with worsening by 4 or more NIHSS points within 72 hours. Results: Fifteen subjects were randomized 3:1 to Target, n=12 or Control, n=3. After treatment, asymptomatic ICH occurred in 3 Target and 1 Control, and sICH was not seen in any study subject. Microspheres reached MCA occlusions in all Target subjects at velocities higher than surrounding residual red blood cell flow: 39.8 plus minus 11.3 vs 28.8 plus minus 13.8 cm/s,P=0.001. In 75% of subjects, microspheres permeated to areas with no pretreatment residual flow, and in 83% residual flow velocity improved at a median of 30 minutes from start of microspheres infusion (range 30 s to 120 minutes) by a median of 17 cm/s (118% above pretreatment values). To provide perspective, current study recanalization rates were compared with the tPA control arm of the CLOTBUST trial: complete recanalization 50% versus 18%, partial 33% versus 33%, none 17% versus 49%, P=0.028. At 2 hours, sustained complete recanalization was 42% versus 13%, P=0.003, and NIHSS scores 0 to 3 were reached by 17% versus 8%, P=0.456. Conclusions: Perflutren microspheres reached and permeated beyond intracranial occlusions with no increase in sICH after systemic thrombolysis suggesting feasibility of further microspheres dose escalation studies and development of drug delivery to tissues with compromised perfusion.
ER  -

ALEXANDROV, Andrei, Robert MIKULÍK, Marc RIBO, Vijay SHARMA, Annabelle LAO, Georgious TSIVGOULIS, Rebecca SUGG, Andrew BARETTO, Paul SIERZENSKI, Marc MALKOFF and James GROTTA. A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke. \textit{Stroke : a journal of cerebral circulation}. Dallas: American Heart Association, 2008, vol.~39, No~5, p.~1464-1469. ISSN~0039-2499. Available from: https://dx.doi.org/10.1161/STROKEAHA.107.505727.

Detailed Information on Publication Record