The PEERLESS Study

NCT05111613 | Completed Results FDA Device

• 1 other identifier: 21-002
• Study Type: interventional
• Target: 692
• Locations: 3 countries
• Sites: 60

Brief Summary

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.

Conditions

Pulmonary Embolism; Pulmonary Thromboembolism

Keywords

PE; pulmonary embolism; thrombectomy; FlowTriever; CDT; Catheter-Directed Thrombolysis

Outcome Measures

Primary Outcomes (1)

• 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: 1. All-cause mortality, or 2. Intracranial hemorrhage (ICH), or 3. Major bleeding per ISTH definition, or 4. Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy, or 5. 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 Outcomes (19)

• Composite Clinical Endpoint Constructed as a 4-Component Win Ratio

  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

Study Arms (3)

Randomized Controlled Trial Cohort - FlowTriever Arm

ACTIVE COMPARATOR

Mechanical thrombectomy for pulmonary embolism using the FlowTriever System.

Device: FlowTriever System

Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm

ACTIVE COMPARATOR

Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system)

Device: Catheter-Directed Thrombolysis

Non-Randomized Absolute Contraindication to Thrombolytics Cohort

OTHER

Mechanical thrombectomy for pulmonary embolism using the FlowTriever System.

Device: FlowTriever System

Interventions

Catheter-Directed Thrombolysis DEVICE

Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system)

Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm

FlowTriever System DEVICE

Mechanical thrombectomy for pulmonary embolism

Non-Randomized Absolute Contraindication to Thrombolytics Cohort; Randomized Controlled Trial Cohort - FlowTriever Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inari Medical: lead

Study Sites (60)

Loma Linda University Health

Loma Linda, California, 92354, United States

Location

Providence St. Joseph Orange

Orange, California, 92868, United States

Location

Huntington Hospital

Pasadena, California, 91105, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Radiology and Imaging Associates

Lakeland, Florida, 33801, United States

Location

Baptist Health South Florida

Miami, Florida, 33176, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Tallahassee Memorial Hospital

Tallahassee, Florida, 32308, United States

Location

University of South Florida Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Ascension Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Ascension St. Vincent Hospital - Indianapolis

Indianapolis, Indiana, 46260, United States

Location

Norton Healthcare

Louisville, Kentucky, 40202, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Ascension St. John Hospital

Detroit, Michigan, 48236, United States

Location

CentraCare St. Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Virtua Lourdes

Camden, New Jersey, 08103, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Northwell Health

Bay Shore, New York, 11706, United States

Location

Gates Vascular Institute

Buffalo, New York, 14203, United States

Location

NewYork-Presbyterian Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina Health

Chapel Hill, North Carolina, 27514, United States

Location

Novant Health New Hanover Regional Medical Center

Wilmington, North Carolina, 28401, United States

Location

Summa Akron City Hospital

Akron, Ohio, 44304, United States

Location

Mercy Health West

Cincinnati, Ohio, 45211, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

OhioHealth Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

St. Luke's University Hospital

Bethlehem, Pennsylvania, 18015, United States

Location

AHN Saint Vincent Hospital

Erie, Pennsylvania, 16544, United States

Location

UPMC Harrisburg

Harrisburg, Pennsylvania, 17101, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19108, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 19140, United States

Location

MUSC Health University Medical Center

Charleston, South Carolina, 29425, United States

Location

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, 29303, United States

Location

Lexington Medical Center

West Columbia, South Carolina, 29169, United States

Location

HCA TriStar Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

Ascension Saint Thomas Hospital

Nashville, Tennessee, 37205, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

HCA Medical City Heart and Spine

Dallas, Texas, 75243, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Memorial Hermann Medical Center

Houston, Texas, 77030, United States

Location

Methodist Main Hospital

San Antonio, Texas, 78229, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

Ascension St. Elizabeth Hospital

Appleton, Wisconsin, 54915, United States

Location

Gundersen Health System

La Crosse, Wisconsin, 54601, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Universtitaetsklinikum Dusseldorf

Düsseldorf, Germany

Location

Herzzentrum Leipzig

Leipzig, Germany

Location

Marien Hospital Wesel GmbH

Wesel, Germany

Location

Inselspital - Universitätsspital Bern

Bern, 3010, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 37703948 BACKGROUND

• 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.

  PMID: 39470698 RESULT

MeSH Terms

Conditions

Pulmonary Embolism

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Ashleigh Willson
• Organization: Inari Medical

ashleigh.willson@stryker.com

925-330-3446

Study Officials

• Wissam Jaber, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Carin Gonsalves, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

• Stefan Stortecky, MD

  Bern University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: November 8, 2021
• Study Start: February 14, 2022
• Primary Completion: March 1, 2024
• Study Completion: April 11, 2024
• Last Updated: November 13, 2025
• Results First Posted: November 13, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (56); CH (1); DE (3)