A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study

doi:10.1016/j.jcin.2015.04.020

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study

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Abstract

Objectives This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Background Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. Methods Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. Results Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. Conclusions Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Original language	English
Article number	2085
Pages (from-to)	1382-1392
Number of pages	11
Journal	JACC: Cardiovascular Interventions
Volume	8
Issue number	10
DOIs	https://doi.org/10.1016/j.jcin.2015.04.020
State	Published - Aug 24 2015

Bibliographical note

Publisher Copyright:
© 2015 American College of Cardiology Foundation.

Funding

This study was funded by a research grant from EKOS, a BTG International group company. Dr. Piazza receives research support from EKOS, Bristol-Myers Squibb, Daiichi-Sankyo, and Janssen. Dr. Jaff is a noncompensated member of the Data Safety and Monitoring Board of EKOS and a Board member of VIVA Physicians, a 501(c)(3) not-for-profit education and research organization. Dr. Ouriel holds equity in and is an employee of Syntactx, which receives fees for core laboratory activities from EKOS. Dr. Jones receives honoraria for serving on the Speaker Bureau of Medtronic and EKOS; and receives consulting fees from Cordis. Drs. Engelhardt, Sterling, Gurley, Bhatheja, Kennedy, Goswami, Natarajan, Rundback, Sadiq, S.K. Liu, Bhalla, Raja, Weinstock, Cynamon, Elmasri, Garcia, Kumar, Ayerdi, Soukas, Kuo, and Goldhaber has received research support from EKOS, a BTG International Group company. Dr. P.-Y. Liu receives consulting fees from EKOS. Dr. Bhatheja is a speaker for St. Jude Medical and Cardiovascular Systems Inc. Dr. Goswami is a consultant for Boston Scientific. Dr. Gurley is a speaker for EKOS. Dr. Weinstock is a consultant for W.L. Gore. Dr. Hohfelder has reported that he has no relationships relevant to the contents of this paper to disclose.

Funders
EKOS Corporation

Keywords

catheter embolectomy
catheter thrombolysis
fibrinolysis
pulmonary embolism
right ventricular failure
thrombolysis

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jcin.2015.04.020

Cite this

@article{4ec5f67f602346759f5783ed80ed72ac,

title = "A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study",

abstract = "Objectives This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Background Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2\%. Methods Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. Results Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10\%). No patient experienced intracranial hemorrhage. Conclusions Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic{\textregistered} Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).",

keywords = "catheter embolectomy, catheter thrombolysis, fibrinolysis, pulmonary embolism, right ventricular failure, thrombolysis",

author = "Gregory Piazza and Benjamin Hohlfelder and Jaff, \{Michael R.\} and Kenneth Ouriel and Engelhardt, \{Tod C.\} and Sterling, \{Keith M.\} and Jones, \{Noah J.\} and Gurley, \{John C.\} and Rohit Bhatheja and Kennedy, \{Robert J.\} and Nilesh Goswami and Kannan Natarajan and John Rundback and Sadiq, \{Immad R.\} and Liu, \{Stephen K.\} and Narinder Bhalla and Raja, \{M. Laiq\} and Weinstock, \{Barry S.\} and Jacob Cynamon and Elmasri, \{Fakhir F.\} and Garcia, \{Mark J.\} and Mark Kumar and Juan Ayerdi and Peter Soukas and William Kuo and Liu, \{Ping Yu\} and Goldhaber, \{Samuel Z.\}",

note = "Publisher Copyright: {\textcopyright} 2015 American College of Cardiology Foundation.",

year = "2015",

month = aug,

day = "24",

doi = "10.1016/j.jcin.2015.04.020",

language = "English",

volume = "8",

pages = "1382--1392",

number = "10",

}

TY - JOUR

T1 - A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism

T2 - The SEATTLE II Study

AU - Piazza, Gregory

AU - Hohlfelder, Benjamin

AU - Jaff, Michael R.

AU - Ouriel, Kenneth

AU - Engelhardt, Tod C.

AU - Sterling, Keith M.

AU - Jones, Noah J.

AU - Gurley, John C.

AU - Bhatheja, Rohit

AU - Kennedy, Robert J.

AU - Goswami, Nilesh

AU - Natarajan, Kannan

AU - Rundback, John

AU - Sadiq, Immad R.

AU - Liu, Stephen K.

AU - Bhalla, Narinder

AU - Raja, M. Laiq

AU - Weinstock, Barry S.

AU - Cynamon, Jacob

AU - Elmasri, Fakhir F.

AU - Garcia, Mark J.

AU - Kumar, Mark

AU - Ayerdi, Juan

AU - Soukas, Peter

AU - Kuo, William

AU - Liu, Ping Yu

AU - Goldhaber, Samuel Z.

PY - 2015/8/24

Y1 - 2015/8/24

N2 - Objectives This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Background Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. Methods Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. Results Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. Conclusions Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

AB - Objectives This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Background Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. Methods Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. Results Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. Conclusions Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

KW - catheter embolectomy

KW - catheter thrombolysis

KW - fibrinolysis

KW - pulmonary embolism

KW - right ventricular failure

KW - thrombolysis

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UR - https://www.scopus.com/pages/publications/84940382264#tab=citedBy

U2 - 10.1016/j.jcin.2015.04.020

DO - 10.1016/j.jcin.2015.04.020

M3 - Article

C2 - 26315743

AN - SCOPUS:84940382264

SN - 1936-8798

VL - 8

SP - 1382

EP - 1392

JO - JACC: Cardiovascular Interventions

JF - JACC: Cardiovascular Interventions

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ER -

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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