The PEERLESS II Study

PEERLESS II: RCT of FlowTriever vs. Anticoagulation Alone in Pulmonary Embolism

This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System plus anticoagulation compared to anticoagulation alone for intermediate-risk acute PE.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Device: FlowTriever System; Drug: Anticoagulation Agents

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie Gourley; Phone Number: 580-400-2590; Email: stephanie.gourley@inarimedical.com

Study Locations

• Belgium
  • Aalst, Belgium
    • Recruiting
    • Onze Lieve Vrouwziekenhuis
    • Contact: Marc Vanderheyden, MD
• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Recruiting
      • Royal Columbian Hospital
      • Contact: Zameer Hirji, MD
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Recruiting
      • Surrey Memorial Hospital
      • Contact: Behrang Homayoon
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver General Hospital
      • Contact: Gordon Finlayson, MD
• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Asger Andersen, MD, PhD
• France
  • Lille, France
    • Recruiting
    • CHU Lille
    • Contact: Gilles Lemesle, Prof. Dr. med.
  • Lyon, France
    • Recruiting
    • Hôpital Louis Pradel
    • Contact: Salim Si-Mohamed, Prof. Dr. med.
  • Marseille, France
    • Recruiting
    • Hôpital Nord Marseille
    • Contact: Marc Laine, Dr. med.
  • Marseille, France
    • Recruiting
    • AP-HM Hopital La Timone
    • Contact: Thomas Cuisset, MD
• Germany
  • Augsburg, Germany
    • Recruiting
    • University Hospital Augsburg
    • Contact: Christian Scheurig-Mὒnkler, Dr.
  • Bad Krozingen, Germany
    • Recruiting
    • Universitäts-Herzzentrum Bad Krozingen
    • Contact: Elias Noory, Dr. med.
  • Berlin, Germany
    • Recruiting
    • Charité Campus Virchow Clinic - Klinik fuer Radiologie
    • Contact: Bernhard Gebauer, Prof. Dr. med.
  • Berlin, Germany
    • Recruiting
    • Unfall Krankenhaus Berlin
    • Contact: Rainer Wasielewski, Dr. med.
  • Cologne, Germany
    • Recruiting
    • University Hospital Cologne
    • Contact: Stephan Rosenkranz, Prof.
  • Dresden, Germany
    • Recruiting
    • HerzZentrum Dresden Universitaetsklinik
    • Contact: Norman Mangner, Prof. Dr. med.
  • Düsseldorf, Germany
    • Recruiting
    • Universitaetsklinikum Dὒsseldorf
    • Contact: Hans Lucas Busch, Dr. med.
  • Essen, Germany
    • Recruiting
    • Universitaetsklinikum Essen
    • Contact: Christos Rammos, Prof. Dr. med.
  • Essen, Germany
    • Recruiting
    • Elisabeth Hospital GmbH
    • Contact: Moaaz Elsharabassy, Dr.
  • Frankfurt, Germany
    • Recruiting
    • CCB Frankfurt
    • Contact: Michael Piorkowski, Dr. med.
  • Hamburg, Germany
    • Recruiting
    • Universitaetsklinikum Hamburg Eppendorf
    • Contact: Fabian Brunner, Prof Dr. Med
  • Heidelberg, Germany
    • Recruiting
    • University Hospital - Heidelberg
    • Contact: Richard Schell, Dr.
  • Homburg, Germany
    • Withdrawn
    • Universitaetsklinikum Saarlandes Homburg
  • Kaiserslautern, Germany
    • Recruiting
    • Westpfalz Klinikum
    • Contact: Burghard Schumacher, Prof.
  • Munich, Germany
    • Recruiting
    • Ludwig Maximilians-University
    • Contact: Konstantin Stark, Prof.
  • Munich, Germany
    • Recruiting
    • Klinikum rechts der Isar (TUM)
    • Contact: Tareq Ibrahim, Prof. Dr.
  • Regensburg, Germany
    • Recruiting
    • University Hospital Regensburg
    • Contact: Stefan Stadler, Prof. Dr. med.
  • Schwerin, Germany
    • Recruiting
    • Helios Kliniken Schwerin
    • Contact: Philipp Hammer, Dr. med.
  • Villingen-Schwenningen, Germany
    • Recruiting
    • Schwarzwald-Baar-Klinikum
    • Contact: Sebastian Ewen, Prof Dr. Med
• Poland
  • Krakow, Poland
    • Terminated
    • John Paul II Hospital
• Spain
  • Madrid, Spain
    • Recruiting
    • Hopital Clinico Universitario San Carlos
    • Contact: Pablo Salinas, Dr. med.
• Switzerland
  • Basel, Switzerland
    • Recruiting
    • Universitaetsspital Basel
    • Contact: Gregor Leibundgut, Dr. med.
  • Bern, Switzerland
    • Recruiting
    • Universitätsspital Bern
    • Contact: Stefan Stortecky, Prof. Dr. med
  • Lucerne, Switzerland
    • Recruiting
    • Luzerner Kantonsspital
    • Contact: Thorsten Grumann, Dr. med.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • UAB Division of Cardiovascular Disease
      • Contact: Samuel McElwee, MD
    • Birmingham, Alabama, United States, 35243
      • Completed
      • Brookwood Medical Center
  • California
    • Pasadena, California, United States, 91105
      • Recruiting
      • Huntington Memorial Hospital
      • Contact: Nikhil Daga, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado, Denver
      • Contact: Todd Bull, MD
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: Akhil Khosla, MD
  • Florida
    • Largo, Florida, United States, 33770
      • Completed
      • HCA FL Largo Medical Center
    • Orlando, Florida, United States, 32803
      • Recruiting
      • AdventHealth Orlando
      • Contact: Barry Weinstock, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Wissam Jaber, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Daniel Schimmel, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Withdrawn
      • Baptist Health Louisville
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Recruiting
      • McLaren Greater Lansing
      • Contact: Ibrahim Shah, MD
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Withdrawn
      • Metropolitan Heart & Vascular Institute
    • Rochester, Minnesota, United States, 55905
      • Withdrawn
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Completed
      • Saint Luke's Hospital of Kansas City
    • Springfield, Missouri, United States, 65804
      • Recruiting
      • Mercy Hospital Springfield
      • Contact: Madhu Kalyan Pendurthi, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Recruiting
      • Nebraska Medical Center
      • Contact: Jason Cook, MD
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Recruiting
      • Virtua Health
      • Contact: Rita Butler, MD
    • Ridgewood, New Jersey, United States, 07450
      • Withdrawn
      • Valley Health
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • SUNY, The University of Buffalo/Gates Vascular
      • Contact: David Zlotnick, MD
    • New York, New York, United States, 10075
      • Recruiting
      • Northwell Health
      • Contact: Bushra Mina, MD
    • Queens, New York, United States, 11418
      • Recruiting
      • Jamaica Hospital
      • Contact: Zoran Lasic, MD
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Jeffrey Bruckel, MD
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Hospital
      • Contact: Daniel Ohngemach, MD
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: Asma Khaliq, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center
      • Contact: Rishi Sukhija, MD
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • The Cleveland Clinic Foundation
      • Contact: Aravinda Nanjundappa, MD
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University - Wexner Medical Center
      • Contact: Richard Gumina, MD
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Recruiting
      • St. Luke's University Hospital
      • Contact: Neal Fitzpatrick, MD
    • Erie, Pennsylvania, United States, 16505
      • Recruiting
      • AHN Saint Vincent Hospital
      • Contact: Orestis Pappas, MD
    • Erie, Pennsylvania, United States, 16507
      • Recruiting
      • UPMC Hamot
      • Contact: Robert Maholic, DO
    • Harrisburg, Pennsylvania, United States, 17101
      • Recruiting
      • UPMC Harrisburg
      • Contact: Torrey Schmidt, DO
    • Philadelphia, Pennsylvania, United States, 19144
      • Recruiting
      • Thomas Jefferson University
      • Contact: Mae West, MD
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The University of Pennsylvania
      • Contact: Sameer Khandhar, MD
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Allegheny Health Network Research Institute
      • Contact: Mithun Chakravarthy
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Heart and Vascular Institute
      • Contact: Catalin Toma, MD
    • York, Pennsylvania, United States, 17403
      • Recruiting
      • Wellspan York Hospital
      • Contact: Paul Tolerico, MD
  • Tennessee
    • Brentwood, Tennessee, United States, 37027
      • Recruiting
      • HCA Tristar
      • Contact: Sam Horr, MD
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • UTMC Knoxville
      • Contact: Chris Walker, MD
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Ascension Saint Thomas Hospital
      • Contact: Jimmy Kerrigan, MD
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Parkland Hospital
      • Contact: Akram Sadeghi, MD
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Texas Health Harris Methodist Hospital
      • Contact: John Hollingsworth, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Methodist Main Hospital
      • Contact: Chandra Kunavarapu, MD
      • Contact: Jeffrey DellaVolpe, MD
    • Temple, Texas, United States, 76508
      • Recruiting
      • Baylor Scott & White - Temple
      • Contact: Tasnim Lat, DO
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Recruiting
      • Inova Fairfax
      • Contact: Jonathan Keung, MD
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Sentara Vascular Specialists
      • Contact: David Dexter, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington
      • Contact: Matthew Abad-Santos, MD
    • Spokane, Washington, United States, 99204
      • Withdrawn
      • Providence Sacred Heart
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Recruiting
      • Charleston Area Medical Center
      • Contact: Shadi Abu-Halimah, MD
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University Ruby Memorial Hospital
      • Contact: Sunil Sharma, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Recruiting
      • Aurora Saint Luke's Medical Center
      • Contact: Khawaja Afzal Ammar, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age at enrollment ≥ 18 years
2. Objective evidence of a proximal filling defect in at least one main or lobar pulmonary artery, as confirmed by CTPA, pulmonary angiography, or other imaging modality
3. RV dysfunction, as defined as one or more of the following: RV/LV ratio ≥ 0.9 or RV dilation or hypokinesis

4. At least two additional risk factors, identified by at least one measure in two separate categories noted below:

   a. Hemodynamic: i. SBP 90-100mmHg ii. Resting heart rate > 100 bpm b. Biomarker: i. Elevated* cardiac troponin (troponin I or troponin T, conventional or high sensitivity) ii. Elevated* BNP or NT-proBNP iii. Elevated venous lactate ≥2 mmol/L * Elevated, meaning at or above the upper limit of normal, per local standards for the assay used c. Respiratory: i. O2 saturation < 90% on room air ii. Supplemental O2 requirement ≥ 4 L/min iii. Respiratory rate ≥ 20 breaths/min iv. mMRC score > 0

5. Symptom onset within 14 days of confirmed PE diagnosis
6. Willing and able to provide informed consent

Exclusion Criteria:

1. Unable to be anticoagulated with heparin, enoxaparin or other parenteral antithrombin

2. Presentation with hemodynamic instability* that meets the high-risk PE definition in the 2019 ESC Guidelines1, including ANY of the following

   1. Cardiac arrest OR
   2. Systolic BP < 90 mmHg or vasopressors required to achieve a BP ≥ 90 mmHg despite adequate filling status, AND end-organ hypoperfusion OR
   3. 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 * Patients who are stable at time of screening or randomization (i.e., SBP ≥ 90 mmHg and adequate organ perfusion without catecholamine or vasopressor infusion) may be included despite initial presentation including temporary, low-dose catecholamines or vasopressors, or temporary fluid resuscitation.
3. Known sensitivity to radiographic contrast agents that, in the Investigator's opinion, cannot be adequately pre-treated
4. 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)
5. End stage medical condition with life expectancy < 3 months, as determined by the Investigator
6. Current participation in another drug or device study that, in the investigator's opinion, would interfere with participation in this study
7. Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis, per 2019 ESC Guidelines1
8. If objective testing was performed*, estimated RV systolic pressure > 70 mmHg on standard of care echocardiography * If clinical suspicion of acute-on-chronic PE, chronic obstruction, or chronic thromboembolism, echocardiographic estimated RVSP must be confirmed ≤70 mmHg to meet eligibility. Pressure assessment not required if Investigator attests to absence of such clinical suspicion
9. Administration of advanced therapies (thrombolytic bolus, thrombolytic drip/infusion, catheter-directed thrombolytic therapy, mechanical thrombectomy, or ECMO) for the index PE event within 30 days prior to enrollment
10. Ventricular arrhythmias refractory to treatment at the time of enrollment
11. Known to have heparin-induced thrombocytopenia (HIT)
12. 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 System per local approved labeling
13. Subject is currently pregnant
14. Subject has previously completed or withdrawn from this study

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FlowTriever; Mechanical thrombectomy for pulmonary embolism using the FlowTriever System.	Device: FlowTriever System; Mechanical Thrombectomy for pulmonary embolism
Active Comparator: Anticoagulation; Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc. Anticoagulants are a group of medications that decrease your blood's ability to clot.	Drug: Anticoagulation Agents; Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc. Anticoagulants are a group of medications that decrease your blood's ability to clot.

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, which are assessed post-randomization:	All-cause mortality by 30 days, or; Clinical deterioration, defined by hemodynamic or respiratory worsening, through discharge or up to 30 days after randomization, whichever is sooner, or; All-cause hospital re-admission by 30 days, or; Bailout therapy, either after a deterioration or after documented failure to progress, through discharge or up to 30 days after randomization, whichever is sooner, or; Change in Dyspnea, by mMRC from Baseline to the 48-hour visit	through discharge or 30 days, whichever is sooner / dyspnea at 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite clinical endpoint constructed as a win ratio hierarchy of the following three components, assessed post randomization:	All-cause mortality, by 30 days, or; Clinical deterioration defined by hemodynamic or respiratory worsening, through discharge or up to 30 days after randomization, whichever is sooner, or; All-cause readmission, by 30 days	up to 30 days
All-cause and PE-related mortality		At 30 and 90 days
All-cause and PE-related readmissions		At 30 and 90 days
Clinical deterioration	defined by hemodynamic or respiratory worsening	Through discharge or up to 30 days after randomization, whichever is sooner
Bailout therapy	either after a deterioration or after documented failure to progress,	Through discharge or up to 30 days after randomization, whichever is sooner
Major Bleeding, defined by the Bleeding Academic Research Consortium (BARC), level 3b, 3c, 5a, or 5b	3b: Overt bleeding plus hemoglobin drop of ≥ 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade, bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid); bleeding requiring intravenous vasoactive agents 3c: Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal), subcategories confirmed by autopsy or imaging or lumbar puncture, intraocular bleed compromising vision. 5a: Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious 5b: Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation	At 30 and 90 days
Dyspnea severity by mMRC score	0, no breathlessness except on strenuous exercise; 1, shortness of breath when hurrying on the level or walking up a slight hill;; 2, walks slower than people of same age on the level because of breathlessness or has to stop to catch breath when walking at their own pace on the level;; 3, stops for breath after walking ∼100 m or after few minutes on the level; and; 4, too breathless to leave the house, or breathless when dressing or undressing	At the 48-hour, 1-month, and 3-month visits
PE-related quality of life, by PEmb-QoL	Pulmonary Embolism Quality of Life: (higher = better)	At the 1- and 3-month visits
General health-related quality of life, by EQ-5D-5L	Higher score = worse	At the 1- and 3-month visits
6-minute walk distance		At the 1-month visit
RV/LV ratio		At the 48-hour visit
Post-PE Impairment diagnosis (PPEI)		Through the 3-month visit

Collaborators and Investigators

• Sponsor: Inari Medical
• Investigators: Principal Investigator: Jay Giri, MD, Penn Medicine; Principal Investigator: Bernhard Gebauer, MD, Charité University Hospital Berlin; Principal Investigator: Felix Mahfoud, MD, Universitaetsspital Basel; Principal Investigator: Frances Mae West, MD, Jefferson Health

Publications and helpful links

General Publications

• Giri J, Mahfoud F, Gebauer B, Andersen A, Friedman O, Gandhi RT, Jaber WA, Pereira K, West FM. PEERLESS II: A Randomized Controlled Trial of Large-Bore Thrombectomy Versus Anticoagulation in Intermediate-Risk Pulmonary Embolism. J Soc Cardiovasc Angiogr Interv. 2024 May 3;3(6):101982. doi: 10.1016/j.jscai.2024.101982. eCollection 2024 Jun.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: September 15, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hematologic Agents; Anticoagulants
• Other Study ID Numbers: 23-001

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