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

A Prospective, Single-Arm, Multi-Center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism; Acute Pulmonary Embolism; Pulmonary Thromboembolism; Massive Pulmonary Embolism; Sub-massive Pulmonary Embolism
• Intervention / Treatment: Drug: recombinant tissue plasminogen activator; Device: EKOS EkoSonic Endovascular System

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
      • Baptist Health
  • California
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Connecticut
    • Hartford, Connecticut, United States
      • Hartford Hospital
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Hospital
  • Florida
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Medical Center
    • Melbourne, Florida, United States, 32901
      • Holmes Regional Medical Center
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Orlando, Florida, United States, 32806
      • Orlando Regional Medical Center
  • Georgia
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
  • Illinois
    • Springfield, Illinois, United States, 62701
      • Prairie Heart Institute
  • Indiana
    • Indianapolis, Indiana, United States
      • St. Vincent Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, Gill Heart Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70006
      • East Jefferson General Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Overlook Medical Center
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Mt. Carmel East
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
  • Texas
    • El Paso, Texas, United States, 79902
      • Providence Memorial and Sierra Medical Center
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Inova Alexandria Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: EkoSonic® Endovascular System; 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.

Drug: recombinant tissue plasminogen activator; Participants will receive 24 mg of r-tPA delivered via the EkoSonic Endovascular Device.; Other Names: Alteplase; r-tPA; t-PA; Device: EKOS EkoSonic Endovascular System; 24 mg of r-tPA will be delivered through the EkoSonic Endovascular System.; Other Names: EkoSonic Endovascular Device; EkoSonic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, within 48 +/- 6 hours of initiation of therapy
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.	From start of study drug infusion up to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Hour 48 after initiation of therapy
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.	Baseline up to Day 30
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.	Baseline up to Day 30
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.	Baseline up to Day 30

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Collaborators: EKOS Corporation
• Investigators: Principal Investigator: Narinder Bhalla, MD, Baptist Health; Principal Investigator: William Kuo, MD, Stanford Hospital and Clinics; Principal Investigator: Stephen K Liu, MD, Memorial Medical Center - Modesto; Principal Investigator: Immad Sidiq, MD, Hartford Hospital; Study Chair: Samuel Z Goldhaber, MD, Brigham and Women's; Principal Investigator: Mark J Garcia, MD, Christiana Hospital; Principal Investigator: Rohit Bhatheja, MD, AdventHealth; Principal Investigator: Robert Kennedy, MD, Holmes Regional Medical Center; Principal Investigator: Fakhir Elmasri, MD, Lakeland Regional Medical Center; Principal Investigator: Barry S Weinstock, MD, Orlando Regional Medical Center; Principal Investigator: Juan Ayerdi, MD, Medical Center of Central Georgia; Principal Investigator: Nilesh Goswami, MD, Prairie Heart Institute - St.John's Hospital; Principal Investigator: Kannan Natarajan, MD, St Vincent's Hospital; Principal Investigator: Tod C Engelhardt, MD, East Jefferson General Hospital; Principal Investigator: Mark Kumar, MD, Overlook Medical Center; Principal Investigator: John Rundback, MD, Holy Name Hospital; Principal Investigator: Jacob Cynamon, MD, Montefiore Medical Center; Principal Investigator: Peter Soukas, MD, The Miriam Hospital; Principal Investigator: Mohammad L Raja, MD, Providence Memorial Hospital - Sierra Vista Hospital; Principal Investigator: Keith M Sterling, MD, INOVA Alexandria; Principal Investigator: John Gurley, MD, University of Kentucky; Principal Investigator: Noah Jones, MD, Mt. Carmel East

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 7, 2012
• Primary Completion (ACTUAL): February 17, 2013
• Study Completion (ACTUAL): February 17, 2013

Study Registration Dates

• First Submitted: January 17, 2012
• First Submitted That Met QC Criteria: January 17, 2012
• First Posted (ESTIMATE): January 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Fibrinolysis; recombinant t-PA; Activase; catheter directed fibrinolysis; ultrasound accelerated fibrinolysis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: EKOS 09