The PEERLESS II Study
- Conditions
- Pulmonary Embolism
- Interventions
- Device: FlowTriever SystemDrug: Anticoagulation Agents
- Registration Number
- NCT06055920
- Lead Sponsor
- Inari Medical
- Brief Summary
This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System plus anticoagulation compared to anticoagulation alone for intermediate-risk acute PE.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1200
-
Age at enrollment ≥ 18 years
-
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
-
RV dysfunction, as defined as one or more of the following: RV/LV ratio ≥ 0.9 or RV dilation or hypokinesis
-
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
-
Symptom onset within 14 days of confirmed PE diagnosis
-
Willing and able to provide informed consent
-
Unable to be anticoagulated with heparin, enoxaparin or other parenteral antithrombin
-
Presentation with hemodynamic instability* that meets the high-risk PE definition in the 2019 ESC Guidelines1, 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 * 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.
-
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)
-
End stage medical condition with life expectancy < 3 months, 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 2019 ESC Guidelines1
-
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
-
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
-
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 System per local approved labeling
-
Subject is currently pregnant
-
Subject has previously completed or withdrawn from this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FlowTriever FlowTriever System Mechanical thrombectomy for pulmonary embolism using the FlowTriever System. Anticoagulation 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.
- Primary Outcome Measures
Name Time Method Composite clinical endpoint constructed as a win ratio, a hierarchy of the following, which are assessed post-randomization: through discharge or 30 days, whichever is sooner / dyspnea at 48 hours * 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
* Dyspnea, by mMRC at the 48-hour visit
- Secondary Outcome Measures
Name Time Method Composite clinical endpoint constructed as a win ratio hierarchy of the following three components, assessed post randomization: up to 30 days * 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 daysAll-cause and PE-related mortality At 30 and 90 days PE-related quality of life, by PEmb-QoL At the 1- and 3-month visits Pulmonary Embolism Quality of Life: (higher = better)
All-cause and PE-related readmissions At 30 and 90 days Major Bleeding, defined by the Bleeding Academic Research Consortium (BARC), level 3b, 3c, 5a, or 5b At 30 and 90 days 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 confirmationDyspnea severity by mMRC score At the 48-hour, 1-month, and 3-month visits 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 undressingRV/LV ratio At the 48-hour visit Clinical deterioration Through discharge or up to 30 days after randomization, whichever is sooner defined by hemodynamic or respiratory worsening
Bailout therapy Through discharge or up to 30 days after randomization, whichever is sooner either after a deterioration or after documented failure to progress,
General health-related quality of life, by EQ-5D-5L At the 1- and 3-month visits Higher score = worse
6-minute walk distance At the 1-month visit Post-PE Impairment diagnosis (PPEI) Through the 3-month visit
Trial Locations
- Locations (83)
UAB Division of Cardiovascular Disease
🇺🇸Birmingham, Alabama, United States
Brookwood Medical Center
🇺🇸Birmingham, Alabama, United States
Huntington Memorial Hospital
🇺🇸Pasadena, California, United States
University of Colorado, Denver
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
HCA FL Largo Medical Center
🇺🇸Largo, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Baptist Health Louisville
🇺🇸Louisville, Kentucky, United States
McLaren Greater Lansing
🇺🇸Lansing, Michigan, United States
Metropolitan Heart & Vascular Institute
🇺🇸Coon Rapids, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Virtua Health
🇺🇸Camden, New Jersey, United States
Valley Health
🇺🇸Ridgewood, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
SUNY, The University of Buffalo/Gates Vascular
🇺🇸Buffalo, New York, United States
Northwell Health
🇺🇸New York, New York, United States
Jamaica Hospital
🇺🇸Queens, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio State University - Wexner Medical Center
🇺🇸Columbus, Ohio, United States
St. Luke's University Hospital
🇺🇸Bethlehem, Pennsylvania, United States
AHN Saint Vincent Hospital
🇺🇸Erie, Pennsylvania, United States
UPMC Hamot
🇺🇸Erie, Pennsylvania, United States
UPMC Harrisburg
🇺🇸Harrisburg, Pennsylvania, United States
The University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Universitäts-Herzzentrum Bad Krozingen
🇩🇪Bad Krozingen, Germany
Allegheny Health Network Research Institute
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Heart and Vascular Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Wellspan York Hospital
🇺🇸York, Pennsylvania, United States
HCA Tristar
🇺🇸Brentwood, Tennessee, United States
UTMC Knoxville
🇺🇸Knoxville, Tennessee, United States
Ascension Saint Thomas Hospital
🇺🇸Nashville, Tennessee, United States
Parkland Hospital
🇺🇸Dallas, Texas, United States
Texas Health Harris Methodist Hospital
🇺🇸Fort Worth, Texas, United States
Methodist Main Hospital
🇺🇸San Antonio, Texas, United States
Baylor Scott & White - Temple
🇺🇸Temple, Texas, United States
Inova Fairfax
🇺🇸Falls Church, Virginia, United States
Sentara Vascular Specialists
🇺🇸Norfolk, Virginia, United States
University of Washington
🇺🇸Seattle, Washington, United States
Providence Sacred Heart
🇺🇸Spokane, Washington, United States
Charleston Area Medical Center
🇺🇸Charleston, West Virginia, United States
West Virginia University Ruby Memorial Hospital
🇺🇸Morgantown, West Virginia, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Onze Lieve Vrouwziekenhuis
🇧🇪Aalst, Belgium
Royal Columbian Hospital
🇨🇦New Westminster, British Columbia, Canada
Surrey Memorial Hospital
🇨🇦Surrey, British Columbia, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Aarhus University Hospital
🇩🇰Aarhus, Denmark
CHU Lille
🇫🇷Lille, France
Hôpital Louis Pradel
🇫🇷Lyon, France
AP-HM Hopital La Timone
🇫🇷Marseille, France
Hôpital Nord Marseille
🇫🇷Marseille, France
University Hospital Augsburg
🇩🇪Augsburg, Germany
Charité Campus Virchow Clinic - Klinik fuer Radiologie
🇩🇪Berlin, Germany
Unfall Krankenhaus Berlin
🇩🇪Berlin, Germany
University Hospital Cologne
🇩🇪Cologne, Germany
HerzZentrum Dresden Universitaetsklinik
🇩🇪Dresden, Germany
Universitaetsklinikum Dὒsseldorf
🇩🇪Düsseldorf, Germany
Elisabeth Hospital GmbH
🇩🇪Essen, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
CCB Frankfurt
🇩🇪Frankfurt, Germany
Universitaetsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
University Hospital - Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Saarlandes Homburg
🇩🇪Homburg, Germany
Westpfalz Klinikum
🇩🇪Kaiserslautern, Germany
Klinikum rechts der Isar (TUM)
🇩🇪Munich, Germany
Ludwig Maximilians-University
🇩🇪Munich, Germany
University Hospital Regensburg
🇩🇪Regensburg, Germany
Helios Kliniken Schwerin
🇩🇪Schwerin, Germany
Schwarzwald-Baar-Klinikum
🇩🇪Villingen-Schwenningen, Germany
John Paul II Hospital
🇵🇱Kraków, Poland
Hopital Clinico Universitario San Carlos
🇪🇸Madrid, Spain
Universitaetsspital Basel
🇨🇭Basel, Switzerland
Universitätsspital Bern
🇨🇭Bern, Switzerland
Luzerner Kantonsspital
🇨🇭Luzern, Switzerland