An International Pulmonary Embolism Registry Using EKOS (KNOCOUT PE)

Retrospective and Prospective International EkoSonic® Registry of the Treatment and Clinical OUTcomes of Patients With Pulmonary Embolism

This registry is designed to understand acoustic pulse thrombolysis (APT) treatment regimens used as standard of care globally for pulmonary embolism. The registry will include individuals who have already received the APT treatment and those that will undergo APT treatment.

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism and Thrombosis
• Intervention / Treatment: Device: EkoSonic Endovascular System with thrombolytic

Detailed Description

For the prospective arm of the registry, a physician will have selected the APT procedure for the treatment of pulmonary embolism. The APT treatment and follow-up assessments are per clinical judgement and institutional standard of care which may vary at each clinical site.

For the retrospective arm of the registry, the investigators will gather data from consecutive cases of individuals who received the APT treatment for pulmonary embolism. Specific baseline, treatment, and long-term health information is collected and de-identified.

• Study Type: Observational
• Enrollment (Actual): 1480

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Medical University of Vienna
• France
  • Besançon, France
    • CHRU jean Minjoz, Pôle cœur-Poumons
  • Marseille, France, 13015
    • Hôpital Nord, APHM
• Germany
  • Mainz, Germany, 55099
    • Johannes Gutenberg Univeristy Mainz
  • Munchen, Germany, 80333
    • Technical University Munchen
• Netherlands
  • Utrecht, Netherlands
    • University Medical Center Uterecht
• Switzerland
  • Bern, Switzerland
    • Swiss Cardiovascular Center
  • Zurich, Switzerland
    • University Hospital Zurich
• Turkey
  • Istanbul, Turkey, 34662
    • Acibadem University School of Medicine
• United Kingdom
  • Exeter, United Kingdom
    • Royal Devon and Exeter Hospital
  • Gillingham, United Kingdom
    • Medway NHS Foundation Trust
  • Headington, United Kingdom, OX3 0BL
    • Oxford University Hospitals
  • London, United Kingdom
    • St. Mary's Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free
  • London, United Kingdom, SE1 7EH
    • Guy's & St Thomas' NHS Foundation Trust
• United States
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Healthfinity, PLLC Advanced Cardiac & Vascular Clinic
  • California
    • Los Angeles, California, United States, 90048
      • Cedars - Sinai
  • Colorado
    • Englewood, Colorado, United States, 80112
      • Radiology Imaging Associates
  • Florida
    • Bradenton, Florida, United States, 34205
      • Bradenton Cardiology Center
    • Delray Beach, Florida, United States, 33484
      • Delray Medical Center
    • Jacksonville, Florida, United States, 32216
      • Memorial Hospital
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Jacksonville, Florida, United States, 32204
      • St. Vincent's Healthcare
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc.
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute, Inc
    • Tampa, Florida, United States, 33613
      • AdventHealth Tampa Pepin Heart Institute
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
    • Augusta, Georgia, United States, 30912
      • Augusta University
    • Marietta, Georgia, United States, 30060
      • WellStar Medical Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Hobart, Indiana, United States, 46342
      • St. Mary Medical Center
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Hospital
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • St. Elizabeth Healthcare
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Worcester, Massachusetts, United States, 01608
      • St. Vincent Hospital/Reliant Medical Group
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Detroit, Michigan, United States, 88236
      • Ascension St. John Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
    • Wyoming, Michigan, United States, 49519
      • Metro Health - University of Michigan Health
  • Mississippi
    • Oxford, Mississippi, United States, 38655
      • Cardiology Associates of Northern Mississippi
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth - Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Healthcare
  • New York
    • Buffalo, New York, United States, 14203
      • University of Buffalo
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45211
      • Mercy Health Cincinnati
    • Cincinnati, Ohio, United States, 45220
      • TriHealth Good Samaritan Bethesda North
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Columbus, Ohio, United States, 43213
      • Mount Caramel East Hospital
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Zanesville, Ohio, United States, 43701
      • Genesis HealthCare System
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network
    • Erie, Pennsylvania, United States, 16502
      • St. Vincent Hospital, Allegheny Health Network
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital, Department of Thoracic Medicine & Surgery
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15219
      • UPMC Hamot
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Lexington Cardiology
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Abilene, Texas, United States, 79601
      • Hendrick Medical Center
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
    • Sugar Land, Texas, United States, 77479
      • Houston Methodist Sugarland
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Inova Alexandria Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialists
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center
    • Spokane, Washington, United States, 99204
      • Inland Imaging
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC
    • Morgantown, West Virginia, United States, 26505
      • West Virginia University Heart & Vascular Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53205
      • Aurora Cardiovascular Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with intermediate-high and high risk pulmonary embolism who are selected to receive treatment using the EKOS device and thrombolytic.

Description

Retrospective Inclusion Criteria:

• Treated with APT procedure between January 1, 2014 and one year prior to site activation
• RV/LV ≥ 1.0 from diagnostic computed tomographic angiography (CTA) or echocardiogram
• PE symptom duration ≤ 14 days
• Troponin elevation

Retrospective Exclusion Criteria:

• Enrollment into the OPTALYSE PE study

Prospective Inclusion Criteria:

• Male or female ≥ 18 years of age and ≤ 80 years of age
• RV/LV ≥ 1.0 from diagnostic computed tomographic angiography (CTA) or echocardiogram
• PE symptom duration ≤ 14 days
• Troponin elevation
• Signed informed consent obtained from participant or legally authorized representative
• Investigator has selected the EKOS device to treat participant with massive or submassive pulmonary embolism

Prospective Exclusion Criteria:

• High-risk for catastrophic bleeding
• Life expectancy < one year

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective; Individuals with intermediate-high or high risk pulmonary embolism who were consecutively treated with the Ekosonic Endovascular System (EKOS) and thrombolytic drug between January 2014 and one year prior to site activation.	Device: EkoSonic Endovascular System with thrombolytic; The device uses ultrasonic waves in combination with clot-dissolving thrombolytic drug to effectively dissolve clots.; Other Names: Acoustic Pulse Thrombolysis; EKOS
Prospective; Individuals who are experiencing intermediate-high or high risk pulmonary embolism where the treating investigator has selected the EKOS device and thrombolytic drug. The duration of ultrasound and volume of thrombolytic drug are selected per physician discretion.	Device: EkoSonic Endovascular System with thrombolytic; The device uses ultrasonic waves in combination with clot-dissolving thrombolytic drug to effectively dissolve clots.; Other Names: Acoustic Pulse Thrombolysis; EKOS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in RV/LV Ratio on Echocardiogram (Matched Pairs as Available)	Difference (percent change) in the measurement of the right ventricular to left ventricular diameters (RV/LV) ratio as measured on baseline echocardiogram to post-procedure echocardiogram (24-48 hours post initiation of therapy).	Baseline to post-procedure (end of procedure through hospital discharge up to 14 days)
Frequency and Safety Outcomes of Subjects Requiring Interventions of Adjunctive Therapies Post-procedure During Hospitalization.	Measured by number of subjects requiring interventions of adjunctive therapies received during post procedure hospitalization through hospital discharge up to 14 days.	Post-procedure hospitalization through hospital discharge up to 14 days
Number of Patients Who Underwent Interventional Therapies Prior to the APT Procedure and Experienced a Non- or Partial- Response.	Measured by number of patients who underwent interventional therapies prior to the APT procedure and experienced a non or partial response.	From date of enrollment up to or until the placement of the Ekos device, on average 48 hours.
Number of Patients Experiencing a SAEs Related to EKOS Device and/or Procedure During First 12 Months Post-APT Procedure.	Number of subjects experiencing a SAE related to EKOS device and/or procedure from time of procedure through the first 12 months post-APT procedure, measured by frequency and severity of events.	From time of APT procedure through 12 months post-procedure.
All-cause Mortality During First 12 Months Post-procedure.	Number of all-cause mortality that occurred from the start of procedure through 12 months post-procedure.	Start of procedure through 12 months post-procedure.
Healthcare Utilization	Summary of healthcare utilization from date of enrollment through discharge.	Measured as time from ICU admission to ICU discharge in hours (from date of enrollment through 12 months post-procedure).
Change in Quality of Life (QOL) as Measured by the Pulmonary Embolism Quality of Life (PEmb-QOL) at the 3 Month and 12 Month Post-hospitalization Follow-up Visits	Reported as percent change in the PEmb-QOL questionnaire score from baseline timepoint to 3 months and 12 months. The PEmb-QOL measures patient's quality of life following pulmonary embolism on a scale of 1 through 5, with lower scores indicating a better outcome.	Measured as percent change in time from baseline assessment at discharge to 3 month and 12 month follow up.
Change in Quality of Life (QOL) as Measured by the EQ-5D-5L VAS, Utility and Misery Scores at the 3-month and 12-month Post-hospitalization Follow-up Visits.	Reported as change in the VAS, Utility and Misery questionnaire scores from baseline timepoint and/or study visit to 3 months and 12 months. The VAS (Visual Analogue Scale) is a one question, unidimensional measure of pain intensity where a subject is asked to rate his pain on a scale of 100 through 1, with 100 indicating the best health imaginable through 1 indicating the worst health imaginable. Higher scores indicate a better outcome. The EQ-5D is a series of questions that measures Quality of Life on a scale of 0 through 5. 0 indicates no problems in daily activities and 5 indicates inability to perform daily activities. The total score is added up and compared to the total scale from 0 to 25, with 0 indicating no problems in daily activities and 25 indicating inability to perform daily activities. A lower score indicates a better outcome.	Reported results include change from baseline to 3 months and 12 months post-procedure for prospective patients.
Number of Patients Needing an IVC Filter Placement	Measured by number patients with an occurrence of needing an IVC filter placement.	From date of procedure through 12 months
Number of Patients Experiencing Adverse Events Classified as Major Bleeding Events During First 12 Months Post-Procedure by Frequency and Severity	Measured by number of patients experiencing adverse events related to major bleeding events from time of procedure through the first 12 months post-procedure by frequency and severity (mild, moderate, severe).	From post-procedure through 12-months post-procedure
Number of Patients Experiencing VTE (Venus Thromboembolytic Events) During First 12 Months Post-Procedure by Frequency and Severity.	Number of patients experiencing events related to VTE from time of procedure through the first 12 months post-procedure by frequency and severity.	From post-procedure through 12-months post-procedure
Diagnosis of Pulmonary Hypertension Diagnosis	New onset pulmonary hypertension defined as mean pulmonary artery pressure greater than 25 mm Hg by echocardiogram that persists at least 3 months after PE.	Analyzed 12 months post-procedure

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Collaborators: BTG International Inc.
• Investigators: Principal Investigator: Keith Sterling, MD, Inova Alexandria Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 8, 2018

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: venous thromboembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism; Thrombosis; Pulmonary Embolism; Embolism and Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents
• Other Study ID Numbers: BTG-001653-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes