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 Thromboembolism
• Intervention / Treatment: Device: FlowTriever System; Device: Catheter-Directed Thrombolysis

• Study Type: Interventional
• Enrollment (Actual): 692
• 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 Healthcare
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens 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
    • St 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
Primary Endpoint: Composite Clinical Endpoint Constructed as a 5-Component Win Ratio	The primary endpoint is a composite constructed as a hierarchical win ratio of the following 5 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, or; ICU admission and ICU length-of-stay during the index hospitalization and following the index procedure. A win ratio larger than 1 indicates that patients who receive treatment with FlowTriever are more likely to have better outcomes as compared to subjects treated with CDT.	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 4-Component Win Ratio	This secondary endpoint is a composite constructed as a hierarchical win ratio of the following 4 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 A win ratio larger than 1 indicates that patients who receive treatment with FlowTriever are more likely to have better outcomes as compared to subjects treated with CDT.	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	Clinical deterioration is defined as documented objective hemodynamic or respiratory worsening that is new (i.e. not present at the time of enrollment). Bailout therapy is an unplanned escalation of therapeutic measures, taken when the patient's condition has not improved or is not improving according to expectations.	Hospital discharge or at 7 days after the index procedure, whichever is sooner
ICU Admission During the Index Hospitalization and Following the Index Procedure		Hospital discharge or at 7 days after the index procedure, whichever is sooner
ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission.		Hospital discharge or at 7 days after the index procedure, whichever is sooner
All Cause Mortality		30 days from index procedure
All-cause and PE-related Readmissions		30 days from index procedure
Device-related Serious Adverse Events	Device-related SAEs included those adjudicated by the CEC to be related to the interventional device.	Through the 30 day visit
Drug-related Serious Adverse Events	Drug-related SAEs included those adjudicated by the CEC to be related to anticoagulation and/or thrombolytics medication.	Through the 30 day visit
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	Assessments of change were made using the same imaging modality at baseline and at the 24-hour visit.	Baseline to 24 hour visit
Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit	The mMRC score is reported on a 0-4 scale with lower scores representing less dyspnea.	At 24 hour visit
Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit	The mMRC score is reported on a 0-4 scale with lower scores representing less dyspnea.	At 30 day visit
Length of Total Hospital Stay		Through 30 days post-procedure
Length of Post-index-procedure Hospital Stay		Through 30 days post-procedure
Pulmonary Embolism Quality of Life (PEmb-QOL) Score at 30 Day Visit	The Pulmonary Embolism Quality of Life (PEmb-QOL) questionnaire is used to assess the quality of life in patients with pulmonary embolism (PE). It is a disease-specific tool designed to evaluate the impact of PE on various aspects of a patient's life, including daily activities, work, social life, and emotional well-being, and is reported on a 0-100 scale with lower scores representing better quality of life.	At 30 day visit
EQ-5D-5L Quality of Life Score at 30 Day Visit	Each of the five dimensions comprising the EQ-5D-5L descriptive system (mobility, self-care, usual activates, pain/discomfort, anxiety/depression) are graded from 1 (no problems) to 5 (extreme problems). A descriptive health state is defined by combining each level for 5 dimensions into a 5-digit code (e.g., 12345) which is then mapped to the health state index score based on a country-specific value set. Health state index scores range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health).	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

General Publications

• Gonsalves CF, Gibson CM, Stortecky S, Alvarez RA, Beam DM, Horowitz JM, Silver MJ, Toma C, Rundback JH, Rosenberg SP, Markovitz CD, Tu T, Jaber WA. Randomized controlled trial of mechanical thrombectomy vs catheter-directed thrombolysis for acute hemodynamically stable pulmonary embolism: Rationale and design of the PEERLESS study. Am Heart J. 2023 Dec;266:128-137. doi: 10.1016/j.ahj.2023.09.002. Epub 2023 Sep 12.
• Jaber WA, Gonsalves CF, Stortecky S, Horr S, Pappas O, Gandhi RT, Pereira K, Giri J, Khandhar SJ, Ammar KA, Lasorda DM, Stegman B, Busch L, Dexter DJ 2nd, Azene EM, Daga N, Elmasri F, Kunavarapu CR, Rea ME, Rossi JS, Campbell J, Lindquist J, Raskin A, Smith JC, Tamlyn TM, Hernandez GA, Rali P, Schmidt TR, Bruckel JT, Camacho JC, Li J, Selim S, Toma C, Basra SS, Bergmark BA, Khalsa B, Zlotnick DM, Castle J, O'Connor DJ, Gibson CM; PEERLESS Committees and Investigators*. Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial. Circulation. 2025 Feb 4;151(5):260-273. doi: 10.1161/CIRCULATIONAHA.124.072364. Epub 2024 Oct 29.

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 (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: PE; pulmonary embolism; thrombectomy; Catheter-Directed Thrombolysis; FlowTriever; CDT
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; 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