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Submassive and Massive Pulmonary Embolism Treatment With Ultrasound Accelerated Thrombolysis Therapy (SEATTLE II)

Primary Purpose

Pulmonary Embolism, Acute Pulmonary Embolism, Sub-massive Pulmonary Embolism

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
recombinant tissue plasminogen activator
EKOS EkoSonic Endovascular System
Sponsored by
Boston Scientific Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Embolism focused on measuring Fibrinolysis, catheter directed fibrinolysis, ultrasound accelerated fibrinolysis, recombinant t-PA, Activase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Computed tomography (CT) evidence of proximal PE (filling defect in at least one main or segmental pulmonary artery)
  • PE symptom duration less than or equal to (<=)14 days
  • Informed consent can be obtained from participant or Legally Authorized Representative (LAR)
  • Massive PE (syncope, systemic arterial hypotension, cardiogenic shock, or resuscitated cardiac arrest) or
  • Submassive PE (RV diameter-to-LV diameter greater than or equal to [>=] 0.9 on contrast-enhanced chest CT)

Exclusion Criteria:

  • Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year
  • Recent (within one month) or active bleeding from a major organ
  • Hematocrit less than (<) 30 percent (%)
  • Platelets < 100 thousand/microliter (mcL)
  • International Normalized Ratio (INR) greater than (>) 3
  • Activated partial thromboplastin time (aPTT) >50 seconds on no anticoagulants
  • Major surgery within seven days of screening for study enrollment
  • Serum creatinine >2 milligrams/deciliter (mg/dL)
  • Clinician deems high-risk for catastrophic bleeding
  • History of heparin-induced thrombocytopenia (HIT)
  • Pregnancy
  • Catheter-based pharmacomechanical treatment for pulmonary embolism within 3 days of study enrollment
  • Systolic blood pressure less than 80 mm Hg despite vasopressor or inotropic support
  • Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR)
  • Evidence of irreversible neurological compromise
  • Life expectancy <30 days
  • Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study
  • Previous enrollment in the SEATTLE study

Sites / Locations

  • Baptist Health
  • Memorial Medical Center
  • Stanford University Medical Center
  • Hartford Hospital
  • Christiana Hospital
  • Lakeland Regional Medical Center
  • Holmes Regional Medical Center
  • Florida Hospital
  • Orlando Regional Medical Center
  • Medical Center of Central Georgia
  • Prairie Heart Institute
  • St. Vincent Hospital
  • University of Kentucky, Gill Heart Institute
  • East Jefferson General Hospital
  • Hackensack University Medical Center
  • Overlook Medical Center
  • Holy Name Hospital
  • Montefiore Medical Center
  • Mt. Carmel East
  • The Miriam Hospital
  • Providence Memorial and Sierra Medical Center
  • Inova Alexandria Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EkoSonic® Endovascular System

Arm Description

Participants will receive a total of 24 milligrams (mg) of recombinant t-PA infusion, at an infusion rate of 1 milligrams/hour (mg/hr) per device (2 mg/hour for bilateral PE) delivered through the EkoSonic® Endovascular System. This regimen allows for a recombinant t-PA infusion time of 24 hours for one catheter and 12 hours for two catheters, respectively.

Outcomes

Primary Outcome Measures

Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy
Change from baseline in RV diameter/LV diameter ratio was determined by contrast-enhanced chest computed tomography (CT) within 48 +/- 6 hours after initiating ultrasound-accelerated catheter-directed fibrinolysis.
Number of Participants With Major Bleeding
Bleeding adverse events were graded (severe or life-threatening, moderate or mild bleeding) according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification. The participant incidence of major bleeding events was defined as GUSTO moderate and severe events occurring within 72 hours after starting the ultrasound-accelerated catheter-directed fibrinolysis procedure. Mild: Does not meet criteria for moderate or severe; Moderate: Requires transfusion - No hemodynamic compromise; and Severe: Bleeding causes hemodynamic compromise and required intervention or intracranial hemorrhage. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Secondary Outcome Measures

Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy
Change in pulmonary artery systolic pressure was assessed by baseline right-heart catheterization compared with right-heart catheterization at the conclusion of ultrasound-accelerated catheter-directed fibrinolysis and estimated by post-procedure transthoracic echocardiography within 48 hours after initiating the procedure.
Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE)
Percentage of participants with symptomatic recurrent PE up to 30 days following the conclusion of the ultrasound-accelerated catheter-directed fibrinolysis procedure, were reported with a Wilson score 95% confidence interval. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Number of Participants Who Died Due to Any Cause
Number of participants who died due to any cause for up to 30 days following the conclusion of the ultrasound-accelerated catheter-directed fibrinolysis procedure, were reported.
Number of Devices That Could Not be Successfully Used for Infusion
Technical complications associated with the use of the EkoSonic device was recorded during catheter placement in the pulmonary artery and during the infusion procedure.

Full Information

First Posted
January 17, 2012
Last Updated
July 15, 2021
Sponsor
Boston Scientific Corporation
Collaborators
EKOS Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01513759
Brief Title
Submassive and Massive Pulmonary Embolism Treatment With Ultrasound Accelerated Thrombolysis Therapy
Acronym
SEATTLE II
Official Title
A Prospective, Single-Arm, Multi-Center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
June 7, 2012 (Actual)
Primary Completion Date
February 17, 2013 (Actual)
Study Completion Date
February 17, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston Scientific Corporation
Collaborators
EKOS Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine if the EKOS EkoSonic® Endovascular Device when used in conjunction with recombinant tissue plasminogen activator (t-PA) as a treatment for acute PE will decrease the ratio of right ventricle (RV) to left ventricle (LV) diameter within 48 =/- 6 hours in participants with massive or submassive PE.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism, Acute Pulmonary Embolism, Sub-massive Pulmonary Embolism, Massive Pulmonary Embolism, Pulmonary Thromboembolism
Keywords
Fibrinolysis, catheter directed fibrinolysis, ultrasound accelerated fibrinolysis, recombinant t-PA, Activase

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EkoSonic® Endovascular System
Arm Type
Experimental
Arm Description
Participants will receive a total of 24 milligrams (mg) of recombinant t-PA infusion, at an infusion rate of 1 milligrams/hour (mg/hr) per device (2 mg/hour for bilateral PE) delivered through the EkoSonic® Endovascular System. This regimen allows for a recombinant t-PA infusion time of 24 hours for one catheter and 12 hours for two catheters, respectively.
Intervention Type
Drug
Intervention Name(s)
recombinant tissue plasminogen activator
Other Intervention Name(s)
r-tPA, t-PA, Alteplase
Intervention Description
Participants will receive 24 mg of r-tPA delivered via the EkoSonic Endovascular Device.
Intervention Type
Device
Intervention Name(s)
EKOS EkoSonic Endovascular System
Other Intervention Name(s)
EkoSonic Endovascular Device, EkoSonic
Intervention Description
24 mg of r-tPA will be delivered through the EkoSonic Endovascular System.
Primary Outcome Measure Information:
Title
Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy
Description
Change from baseline in RV diameter/LV diameter ratio was determined by contrast-enhanced chest computed tomography (CT) within 48 +/- 6 hours after initiating ultrasound-accelerated catheter-directed fibrinolysis.
Time Frame
Baseline, within 48 +/- 6 hours of initiation of therapy
Title
Number of Participants With Major Bleeding
Description
Bleeding adverse events were graded (severe or life-threatening, moderate or mild bleeding) according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification. The participant incidence of major bleeding events was defined as GUSTO moderate and severe events occurring within 72 hours after starting the ultrasound-accelerated catheter-directed fibrinolysis procedure. Mild: Does not meet criteria for moderate or severe; Moderate: Requires transfusion - No hemodynamic compromise; and Severe: Bleeding causes hemodynamic compromise and required intervention or intracranial hemorrhage. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame
From start of study drug infusion up to 72 hours
Secondary Outcome Measure Information:
Title
Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy
Description
Change in pulmonary artery systolic pressure was assessed by baseline right-heart catheterization compared with right-heart catheterization at the conclusion of ultrasound-accelerated catheter-directed fibrinolysis and estimated by post-procedure transthoracic echocardiography within 48 hours after initiating the procedure.
Time Frame
Baseline, Hour 48 after initiation of therapy
Title
Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE)
Description
Percentage of participants with symptomatic recurrent PE up to 30 days following the conclusion of the ultrasound-accelerated catheter-directed fibrinolysis procedure, were reported with a Wilson score 95% confidence interval. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame
Baseline up to Day 30
Title
Number of Participants Who Died Due to Any Cause
Description
Number of participants who died due to any cause for up to 30 days following the conclusion of the ultrasound-accelerated catheter-directed fibrinolysis procedure, were reported.
Time Frame
Baseline up to Day 30
Title
Number of Devices That Could Not be Successfully Used for Infusion
Description
Technical complications associated with the use of the EkoSonic device was recorded during catheter placement in the pulmonary artery and during the infusion procedure.
Time Frame
Baseline up to Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Computed tomography (CT) evidence of proximal PE (filling defect in at least one main or segmental pulmonary artery) PE symptom duration less than or equal to (<=)14 days Informed consent can be obtained from participant or Legally Authorized Representative (LAR) Massive PE (syncope, systemic arterial hypotension, cardiogenic shock, or resuscitated cardiac arrest) or Submassive PE (RV diameter-to-LV diameter greater than or equal to [>=] 0.9 on contrast-enhanced chest CT) Exclusion Criteria: Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year Recent (within one month) or active bleeding from a major organ Hematocrit less than (<) 30 percent (%) Platelets < 100 thousand/microliter (mcL) International Normalized Ratio (INR) greater than (>) 3 Activated partial thromboplastin time (aPTT) >50 seconds on no anticoagulants Major surgery within seven days of screening for study enrollment Serum creatinine >2 milligrams/deciliter (mg/dL) Clinician deems high-risk for catastrophic bleeding History of heparin-induced thrombocytopenia (HIT) Pregnancy Catheter-based pharmacomechanical treatment for pulmonary embolism within 3 days of study enrollment Systolic blood pressure less than 80 mm Hg despite vasopressor or inotropic support Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR) Evidence of irreversible neurological compromise Life expectancy <30 days Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study Previous enrollment in the SEATTLE study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Narinder Bhalla, MD
Organizational Affiliation
Baptist Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William Kuo, MD
Organizational Affiliation
Stanford Hospital and Clinics
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen K Liu, MD
Organizational Affiliation
Memorial Medical Center - Modesto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Immad Sidiq, MD
Organizational Affiliation
Hartford Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Samuel Z Goldhaber, MD
Organizational Affiliation
Brigham and Women's
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mark J Garcia, MD
Organizational Affiliation
Christiana Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rohit Bhatheja, MD
Organizational Affiliation
AdventHealth
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert Kennedy, MD
Organizational Affiliation
Holmes Regional Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fakhir Elmasri, MD
Organizational Affiliation
Lakeland Regional Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barry S Weinstock, MD
Organizational Affiliation
Orlando Regional Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Juan Ayerdi, MD
Organizational Affiliation
Medical Center of Central Georgia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nilesh Goswami, MD
Organizational Affiliation
Prairie Heart Institute - St.John's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kannan Natarajan, MD
Organizational Affiliation
St Vincent's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tod C Engelhardt, MD
Organizational Affiliation
East Jefferson General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark Kumar, MD
Organizational Affiliation
Overlook Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Rundback, MD
Organizational Affiliation
Holy Name Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jacob Cynamon, MD
Organizational Affiliation
Montefiore Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Soukas, MD
Organizational Affiliation
The Miriam Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mohammad L Raja, MD
Organizational Affiliation
Providence Memorial Hospital - Sierra Vista Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Keith M Sterling, MD
Organizational Affiliation
Inova Alexandria
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Gurley, MD
Organizational Affiliation
University of Kentucky
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Noah Jones, MD
Organizational Affiliation
Mt. Carmel East
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baptist Health
City
Montgomery
State/Province
Alabama
ZIP/Postal Code
36116
Country
United States
Facility Name
Memorial Medical Center
City
Modesto
State/Province
California
ZIP/Postal Code
95355
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Hartford Hospital
City
Hartford
State/Province
Connecticut
Country
United States
Facility Name
Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
Lakeland Regional Medical Center
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
Holmes Regional Medical Center
City
Melbourne
State/Province
Florida
ZIP/Postal Code
32901
Country
United States
Facility Name
Florida Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Orlando Regional Medical Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Medical Center of Central Georgia
City
Macon
State/Province
Georgia
ZIP/Postal Code
31201
Country
United States
Facility Name
Prairie Heart Institute
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62701
Country
United States
Facility Name
St. Vincent Hospital
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
University of Kentucky, Gill Heart Institute
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
East Jefferson General Hospital
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Overlook Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Holy Name Hospital
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Mt. Carmel East
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
Facility Name
The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Providence Memorial and Sierra Medical Center
City
El Paso
State/Province
Texas
ZIP/Postal Code
79902
Country
United States
Facility Name
Inova Alexandria Hospital
City
Alexandria
State/Province
Virginia
ZIP/Postal Code
22304
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27913777
Citation
Sadiq I, Goldhaber SZ, Liu PY, Piazza G; Submassive and Massive Pulmonary Embolism Treatment with Ultrasound AcceleraTed ThromboLysis ThErapy (SEATTLE II) Investigators. Risk factors for major bleeding in the SEATTLE II trial. Vasc Med. 2017 Feb;22(1):44-50. doi: 10.1177/1358863X16676355. Epub 2017 Jan 31.
Results Reference
derived
PubMed Identifier
26315743
Citation
Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, Jones NJ, Gurley JC, Bhatheja R, Kennedy RJ, Goswami N, Natarajan K, Rundback J, Sadiq IR, Liu SK, Bhalla N, Raja ML, Weinstock BS, Cynamon J, Elmasri FF, Garcia MJ, Kumar M, Ayerdi J, Soukas P, Kuo W, Liu PY, Goldhaber SZ; SEATTLE II Investigators. 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. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-1392. doi: 10.1016/j.jcin.2015.04.020.
Results Reference
derived

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Submassive and Massive Pulmonary Embolism Treatment With Ultrasound Accelerated Thrombolysis Therapy

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