The PEERLESS Study (PEERLESS)

A prospective, multicenter, randomized controlled trial of the FlowTriever System compared to Catheter-Directed Thrombolysis (CDT) for use in the treatment of acute pulmonary embolism. The trial includes a non-randomized cohort of subjects with an absolute contraindication to thrombolysis.

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism; Pulmonary Thrombo-embolism
• Intervention / Treatment: Device: FlowTriever System; Device: Catheter-Directed Thrombolysis

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Düsseldorf, Germany
    • Universtitaetsklinikum Dusseldorf
  • Leipzig, Germany
    • Herzzentrum Leipzig
  • Wesel, Germany
    • Marien Hospital Wesel GmbH
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital - Universitätsspital Bern
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health
    • Orange, California, United States, 92868
      • Providence St. Joseph Orange
    • Pasadena, California, United States, 91105
      • Huntington Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Lakeland, Florida, United States, 33801
      • Radiology and Imaging Associates
    • Miami, Florida, United States, 33176
      • Baptist Health South Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Ascension Alexian Brothers Medical Center
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Ascension St. Vincent Hospital - Indianapolis
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Heralthcare
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Ascension St. John Hospital
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare St. Cloud Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Virtua Lourdes
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Bay Shore, New York, United States, 11706
      • Northwell Health
    • Buffalo, New York, United States, 14203
      • Gates Vascular Institute
    • New York, New York, United States, 10032
      • NewYork-Presbyterian Columbia University Irving Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Health
    • Wilmington, North Carolina, United States, 28401
      • Novant Health New Hanover Regional Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital
    • Cincinnati, Ohio, United States, 45211
      • Mercy Health West
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43214
      • OhioHealth Riverside Methodist Hospital
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Hospital
    • Erie, Pennsylvania, United States, 16544
      • AHN Saint Vincent Hospital
    • Harrisburg, Pennsylvania, United States, 17101
      • UPMC Harrisburg
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19108
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 19140
      • UPMC Presbyterian
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Health University Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Healthcare System
    • West Columbia, South Carolina, United States, 29169
      • Lexington Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • HCA TriStar Centennial Medical Center
    • Nashville, Tennessee, United States, 37205
      • Ascension Saint Thomas Hospital
  • Texas
    • Dallas, Texas, United States, 75243
      • HCA Medical City Heart and Spine
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Memorial Hermann Medical Center
    • San Antonio, Texas, United States, 78229
      • Methodist Main Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center
  • Wisconsin
    • Appleton, Wisconsin, United States, 54915
      • Ascension St. Elizabeth Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health System
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Subjects must meet each of the following criteria to be included in the study:

• Age ≥ 18 years
• Echo, computed tomographic pulmonary angiography (CTPA), or pulmonary angiographic evidence of any proximal filling defect in at least one main or lobar pulmonary artery
• Including ALL of the following: Clinical signs and symptoms consistent with acute PE, or PESI class III-V, or sPESI ≥1; AND Hemodynamically stable AND; RV dysfunction on echocardiography or CT; AND Any one or more of the following present at the time of diagnosis: Elevated cardiac troponin levels; History of heart failure; History of chronic lung disease; Heart rate ≥110 beats per minute; SBP <100mmHg; Respiratory rate ≥30 breaths per minute; O2 saturation <90%; Syncope related to PE; Elevated Lactate
• Intervention planned to begin within 72 hours of the later of either: confirmed PE diagnosis; OR if transferring from another hospital, arrival at the treating hospital
• Symptom onset within 14 days of confirmed PE diagnosis

Exclusion Criteria

Subjects will be excluded from the study for any of the following criteria:

• Unable to anticoagulate with heparin, enoxaparin or other parenteral antithrombin
• Index presentation with hemodynamic instability that are part of the high-risk PE definition in the ESC Guidelines 2019, including ANY of the following: cardiac arrest; OR systolic BP < 90 mmHg or vasopressors required to achieve a BP ≥90 mmHg despite adequate filling status, AND end-organ hypoperfusion; OR systolic BP < 90 mmHg or systolic BP drop ≥40 mmHg, lasting longer than 15 min and not caused by new-onset arrhythmia, hypovolemia, or sepsis
• Known sensitivity to radiographic contrast agents that, in the Investigator's opinion, cannot be adequately pre-treated
• Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the patient is not appropriate for catheter-based intervention (e.g. inability to navigate to target location, clot limited to segmental/subsegmental distribution, predominately chronic clot)
• Patient has right heart clot in transit identified at baseline screening
• Life expectancy < 30 days (e.g. stage 4 cancer or severe COVID-19 infection), as determined by the Investigator
• Current participation in another drug or device study that, in the Investigator's opinion, would interfere with participation in this study
• Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis, per ESC 2019 guidelines
• Invasive systolic PA pressure ≥70 mmHg prior to study device entering the body
• Administration of bolus or drip/infusion thrombolytic therapy or mechanical thrombectomy for the index PE event within 48 hours prior to enrollment
• Ventricular arrhythmias refractory to treatment at the time of enrollment
• Known to have heparin-induced thrombocytopenia (HIT)
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments). This includes a contraindication to use of FlowTriever or CDT System (for example, EKOS System) per local approved labeling
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Randomized Controlled Trial Cohort - FlowTriever Arm; Mechanical thrombectomy for pulmonary embolism using the FlowTriever System.	Device: FlowTriever System; Mechanical thrombectomy for pulmonary embolism
Active Comparator: Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm; Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system)	Device: Catheter-Directed Thrombolysis; Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system)
Other: Non-Randomized Absolute Contraindication to Thrombolytics Cohort; Mechanical thrombectomy for pulmonary embolism using the FlowTriever System.	Device: FlowTriever System; Mechanical thrombectomy for pulmonary embolism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite clinical endpoint constructed as a win ratio, a hierarchy of the following:	All-cause mortality, or; Intracranial hemorrhage (ICH), or; Major bleeding per ISTH definition, or; Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy, or; ICU admission and ICU length-of-stay during the index hospitalization and following the index procedure.	Hospital discharge or at 7 days after the index procedure, whichever is sooner

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite clinical endpoint constructed as a win ratio hierarchy of the following four components:	All-cause mortality, or; Intracranial hemorrhage (ICH), or; Major bleeding per ISTH definition, or; Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy	Hospital discharge or at 7 days after the index procedure, whichever is sooner
All-cause mortality		Hospital discharge or at 7 days after the index procedure, whichever is sooner
Intracranial hemorrhage (ICH)		Hospital discharge or at 7 days after the index procedure, whichever is sooner
Major bleeding per ISTH definition		Hospital discharge or at 7 days after the index procedure, whichever is sooner
Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy		Hospital discharge or at 7 days after the index procedure, whichever is sooner
ICU admission and ICU length of stay during the index hospitalization and following the index procedure		Hospital discharge or at 7 days after the index procedure, whichever is sooner
All cause mortality		30 days from index procedure
PE-related and all-cause readmission		30 days from index procedure
Device and drug-related serious adverse events		30 days from index procedure
Clinically Relevant Non-Major (CRNM) and Minor bleeding events		Hospital discharge or at 7 days after the index procedure, whichever is sooner
Change in right-ventricular/left-ventricular (RV/LV) ratio, as measured by echocardiography or CT		Baseline to 24 hour visit
Modified Medical Research Council (mMRC) dyspnea score	The range of scores is zero to four (worse)	At 24 hour and 30 day visits
Length of total hospital stay and post-index-procedure hospital stay		To a maximum of 30 days
Pulmonary Embolism Quality of Life (PEmb-QOL)		At 30 day visit
EQ-5D-5L Quality of Life		At 30 day visit

Collaborators and Investigators

• Sponsor: Inari Medical
• Investigators: Principal Investigator: Carin Gonsalves, MD, Thomas Jefferson University; Principal Investigator: Wissam Jaber, MD, Emory University; Principal Investigator: Stefan Stortecky, MD, Bern university hospital

Publications and helpful links

Helpful Links

• Study design publication

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: October 15, 2021
• First Submitted That Met QC Criteria: October 27, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: PE; pulmonary embolism; thrombectomy; Catheter-Directed Thrombolysis; FlowTriever; CDT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Pulmonary Embolism
• Other Study ID Numbers: 21-002

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