An International Pulmonary Embolism Registry Using EKOS (KNOCOUT PE)

• ClinicalTrials.gov Identifier: NCT03426124
• Recruitment Status: Completed
• First Posted: February 8, 2018
• Results First Posted: February 22, 2023
• Last Update Posted: February 22, 2023
• Sponsor: Boston Scientific Corporation
• Collaborator: BTG International Inc.
• Information provided by (Responsible Party): Boston Scientific Corporation

Tracking Information

• First Submitted Date: January 29, 2018
• First Posted Date: February 8, 2018
• Results First Submitted Date: October 6, 2021
• Results First Posted Date: February 22, 2023
• Last Update Posted Date: February 22, 2023
• Actual Study Start Date: March 1, 2018
• Actual Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2022)

• Change in RV/LV Ratio on Echocardiogram (Matched Pairs as Available) [ Time Frame: Baseline to post-procedure (end of procedure through hospital discharge up to 14 days) ]
  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).
• Frequency and Safety Outcomes of Subjects Requiring Interventions of Adjunctive Therapies Post-procedure During Hospitalization. [ Time Frame: Post-procedure hospitalization through hospital discharge up to 14 days ]
  Measured by number of subjects requiring interventions of adjunctive therapies received during 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. [ Time Frame: From date of enrollment up to or until the placement of the Ekos device, on average 48 hours. ]
  Measured by number of patients who underwent interventional therapies prior to the APT procedure and experienced a non or partial response.
• Number of Patients Experiencing a SAEs Related to EKOS Device and/or Procedure During First 12 Months Post-APT Procedure. [ Time Frame: From time of APT procedure through 12 months post-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.
• All-cause Mortality During First 12 Months Post-procedure. [ Time Frame: Start of procedure through 12 months post-procedure. ]
  Number of all-cause mortality that occurred from the start of procedure through 12 months post-procedure.
• Healthcare Utilization [ Time Frame: Measured as time from ICU admission to ICU discharge in hours (from date of enrollment through 12 months post-procedure). ]
  Summary of healthcare utilization from date of enrollment through discharge.
• 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 [ Time Frame: Measured as percent change in time from baseline assessment at discharge to 3 month and 12 month follow up. ]
  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.
• 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. [ Time Frame: Reported results include change from baseline to 3 months and 12 months post-procedure for prospective patients. ]
  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.
• Number of Patients Needing an IVC Filter Placement [ Time Frame: From date of procedure through 12 months ]
  Measured by number patients with an occurrence of needing an IVC filter placement.
• Number of Patients Experiencing Adverse Events Classified as Major Bleeding Events During First 12 Months Post-Procedure by Frequency and Severity [ Time Frame: From post-procedure through 12-months post-procedure ]
  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).
• Number of Patients Experiencing VTE (Venus Thromboembolytic Events) During First 12 Months Post-Procedure by Frequency and Severity. [ Time Frame: From post-procedure through 12-months post-procedure ]
  Number of patients experiencing events related to VTE from time of procedure through the first 12 months post-procedure by frequency and severity.
• Diagnosis of Pulmonary Hypertension Diagnosis [ Time Frame: Analyzed 12 months post-procedure ]
  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.

Original Primary Outcome Measures (submitted: February 1, 2018)

• Change in the ratio of the measurement of the right ventricular to left ventricular diameters (RV/LV) as measured by echocardiogram [ Time Frame: Baseline to 24 hours after the start of the APT procedure ]
• Persistence of pulmonary hypertension defined as mean pulmonary artery pressure greater than 25mm Hg by echocardiogram [ Time Frame: 6 months after PE diagnosis ]
  Measured by number of frequency and severity
• Other urgent interventions for index PE [ Time Frame: From date of enrollment through hospital discharge, assessed up to 30 days ]
  Measured by number of interventions
• Number of patients with non or partial response to other interventional procedures with APT procedure as adjunctive for index PE [ Time Frame: From date of enrollment through hospital discharge, assessed up to 30 days ]
• Serious adverse experiences (SAE) related to the device and procedure, major bleeding, and venous thromboembolic disease (VTE) events during index hospitalization [ Time Frame: From date of enrollment through hospital discharge, assessed up to 30 days ]
  Measured by frequency and severity
• Recurrent symptomatic VTE and bleeding events [ Time Frame: After the index hospital discharge and during first 12 months ]
  Measured by frequency and duration of stay
• All-cause mortality: PE, stroke, cardiac, malignancy, other [ Time Frame: 12 months after index procedure ]
• Healthcare utilization during hospitalization [ Time Frame: From date of enrollment through hospital discharge, assessed up to 30 days ]
• Quality of life (QOL) as measured by the Pulmonary Embolism Quality of Life (PEmb-QOL) at all post-hospitalization follow-up visits [ Time Frame: 12 months after index procedure ]
• Quality of life (QOL) as measured by the EuroQol five dimension five level questionnaire (EQ-5D-5L) at all post-hospitalization follow-up visits [ Time Frame: 12 months after index procedure ]
• IVC filter placement [ Time Frame: From date of enrollment through hospital discharge, assessed up to 30 days ]
  Measured by number of occurrences

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An International Pulmonary Embolism Registry Using EKOS
• Official Title: Retrospective and Prospective International EkoSonic® Registry of the Treatment and Clinical OUTcomes of Patients With Pulmonary Embolism
• Brief Summary: 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.

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 [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Other
• Target Follow-Up Duration: 1 Year
• Biospecimen: Not Provided
• 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.
• Condition: Pulmonary Embolism and Thrombosis

Intervention

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

Study Groups/Cohorts

• 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.
  Intervention: Device: EkoSonic Endovascular System with thrombolytic
• 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.
  Intervention: Device: EkoSonic Endovascular System with thrombolytic

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 20, 2022): 1480
• Original Estimated Enrollment (submitted: February 1, 2018): 1500
• Actual Study Completion Date: September 30, 2020
• Actual Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Germany, Netherlands, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03426124
• Other Study ID Numbers: BTG-001653-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Boston Scientific Corporation
• Original Responsible Party: EKOS Corporation
• Current Study Sponsor: Boston Scientific Corporation
• Original Study Sponsor: EKOS Corporation
• Collaborators: BTG International Inc.

Investigators

• Principal Investigator: Keith Sterling, MD; Inova Alexandria Hospital

• PRS Account: Boston Scientific Corporation
• Verification Date: May 2022