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: Active, not 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 Locations

• Belgium
  • Aalst, Belgium
    • Onze Lieve Vrouwziekenhuis
• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Royal Columbian Hospital
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Surrey Memorial Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
• France
  • Lille, France
    • CHU Lille
  • Lyon, France
    • Hôpital Louis Pradel
  • Marseille, France
    • Hôpital Nord Marseille
  • Marseille, France
    • AP-HM Hopital La Timone
• Germany
  • Augsburg, Germany
    • University Hospital Augsburg
  • Bad Krozingen, Germany
    • Universitäts-Herzzentrum Bad Krozingen
  • Berlin, Germany
    • Charité Campus Virchow Clinic - Klinik fuer Radiologie
  • Berlin, Germany
    • Unfall Krankenhaus Berlin
  • Cologne, Germany
    • University Hospital Cologne
  • Dresden, Germany
    • HerzZentrum Dresden Universitaetsklinik
  • Düsseldorf, Germany
    • Universitaetsklinikum Dὒsseldorf
  • Essen, Germany
    • Universitaetsklinikum Essen
  • Essen, Germany
    • Elisabeth Hospital GmbH
  • Frankfurt, Germany
    • CCB Frankfurt
  • Hamburg, Germany
    • Universitaetsklinikum Hamburg Eppendorf
  • Heidelberg, Germany
    • University Hospital - Heidelberg
  • Kaiserslautern, Germany
    • Westpfalz Klinikum
  • Munich, Germany
    • Klinikum rechts der Isar (TUM)
  • Munich, Germany
    • Ludwig Maximilians-University
  • Regensburg, Germany
    • University Hospital Regensburg
  • Villingen-Schwenningen, Germany
    • Schwarzwald-Baar-Klinikum
• Spain
  • Madrid, Spain
    • Hopital Clinico Universitario San Carlos
• Switzerland
  • Basel, Switzerland
    • Universitaetsspital Basel
  • Bern, Switzerland
    • Universitätsspital Bern
  • Lucerne, Switzerland
    • Luzerner Kantonsspital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Brookwood Medical Center
    • Birmingham, Alabama, United States, 35205
      • UAB Division of Cardiovascular Disease
  • California
    • Pasadena, California, United States, 91105
      • Huntington Memorial Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Largo, Florida, United States, 33770
      • HCA FL Largo Medical Center
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Michigan
    • Lansing, Michigan, United States, 48910
      • McLaren Greater Lansing
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Nebraska Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Virtua Health
  • New York
    • Buffalo, New York, United States, 14203
      • SUNY, The University of Buffalo/Gates Vascular
    • New York, New York, United States, 10075
      • Northwell Health
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University - Wexner Medical Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Hospital
    • Erie, Pennsylvania, United States, 16507
      • UPMC Hamot
    • Erie, Pennsylvania, United States, 16505
      • AHN Saint Vincent Hospital
    • Harrisburg, Pennsylvania, United States, 17101
      • UPMC Harrisburg
    • Philadelphia, Pennsylvania, United States, 19144
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • The University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Heart and Vascular Institute
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Research Institute
    • York, Pennsylvania, United States, 17403
      • WellSpan York Hospital
  • Tennessee
    • Brentwood, Tennessee, United States, 37027
      • HCA Tristar
    • Knoxville, Tennessee, United States, 37920
      • UTMC Knoxville
    • Nashville, Tennessee, United States, 37203
      • Ascension Saint Thomas Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Hospital
    • Fort Worth, Texas, United States, 76104
      • Texas Health Harris Methodist Hospital
    • San Antonio, Texas, United States, 78229
      • Methodist Main Hospital
    • Temple, Texas, United States, 76508
      • Baylor Scott & White - Temple
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Charleston Area Medical Center
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Ruby Memorial Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center

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 (Actual): July 30, 2026
• Study Completion (Estimated): October 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): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 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