The PEERLESS II Study

Pulmonary Embolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06055920
• Other study ID #: 23-001
• Status: Recruiting
• Phase: N/A
• Start date: November 17, 2023
• Est. completion date: July 2026

Study information

• Verified date: May 2024
• Source: Inari Medical
• Contact: Cassandra Gamble
• Phone: 651-900-5294
• Email: cassandra.gamble[@]inarimedical.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Device:
• FlowTriever System
Mechanical Thrombectomy for pulmonary embolism

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.

Locations

Country	Name	City	State
Belgium	Onze Lieve Vrouwziekenhuis	Aalst
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Surrey Memorial Hospital	Surrey	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
France	CHU Lille	Lille
France	Hôpital Louis Pradel	Lyon
France	AP-HM Hopital La Timone	Marseille
France	Hôpital Nord Marseille	Marseille
Germany	Universitäts-Herzzentrum Bad Krozingen	Bad Krozingen
Germany	Charité Campus Virchow Clinic - Klinik fuer Radiologie	Berlin
Germany	Unfall Krankenhaus Berlin	Berlin
Germany	University Hospital Cologne	Cologne
Germany	Universitaetsklinikum D?sseldorf	Düsseldorf
Germany	Universitaetsklinikum Essen	Essen
Germany	CCB Frankfurt	Frankfurt
Germany	Universitaetsklinikum Hamburg Eppendorf	Hamburg
Germany	University Hospital - Heidelberg	Heidelberg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Universitaetsklinikum Saarlandes Homburg	Homburg
Germany	Universitaetsklinikum Jena	Jena
Germany	Westpfalz Klinikum	Kaiserslautern
Germany	Universitaetsklinikum Koeln	Koeln
Germany	Ludwig Maximilians-University	Munich
Germany	Universitaetsklinikum Regensburg	Regensburg
Germany	Helios Kliniken Schwerin	Schwerin
Germany	Schwarzwald-Baar-Klinikum	Villingen-Schwenningen
Poland	John Paul II Hospital	Kraków
Spain	Hopital Clinico Universitario San Carlos	Madrid
Switzerland	Universitaetsspital Basel	Basel
Switzerland	Universitätsspital Bern	Bern
Switzerland	Luzerner Kantonsspital	Luzern
Switzerland	Kantonspital Sankt Gallen	Sankt Gallen
United States	Emory University	Atlanta	Georgia
United States	University of Colorado, Denver	Aurora	Colorado
United States	St. Luke's University Hospital	Bethlehem	Pennsylvania
United States	Brookwood Medical Center	Birmingham	Alabama
United States	UAB Division of Cardiovascular Disease	Birmingham	Alabama
United States	HCA Tristar	Brentwood	Tennessee
United States	Montefiore Medical Center	Bronx	New York
United States	SUNY, The University of Buffalo/Gates Vascular	Buffalo	New York
United States	Virtua Health	Camden	New Jersey
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	Northwestern University	Chicago	Illinois
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	Metropolitan Heart & Vascular Institute	Coon Rapids	Minnesota
United States	Parkland Hospital	Dallas	Texas
United States	Detroit Medical Center	Detroit	Michigan
United States	AHN Saint Vincent Hospital	Erie	Pennsylvania
United States	UPMC Hamot	Erie	Pennsylvania
United States	Inova Fairfax	Falls Church	Virginia
United States	Texas Health Harris Methodist Hospital	Fort Worth	Texas
United States	UPMC Harrisburg	Harrisburg	Pennsylvania
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	UTMC Knoxville	Knoxville	Tennessee
United States	McLaren Greater Lansing	Lansing	Michigan
United States	Sparrow Hospital	Lansing	Michigan
United States	HCA FL Largo Medical Center	Largo	Florida
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Texas Tech / UMC	Lubbock	Texas
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	West Virginia University Ruby Memorial Hospital	Morgantown	West Virginia
United States	Ascension Saint Thomas Hospital Midtown	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Northwell Health	New York	New York
United States	Sentara Vascular Specialists	Norfolk	Virginia
United States	Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth Orlando	Orlando	Florida
United States	Huntington Memorial Hospital	Pasadena	California
United States	The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Allegheny Health Network Research Institute	Pittsburgh	Pennsylvania
United States	UPMC Heart and Vascular Institute	Pittsburgh	Pennsylvania
United States	The Heart Hospital of Baylor Plano	Plano	Texas
United States	Jamaica Hospital	Queens	New York
United States	Valley Health	Ridgewood	New Jersey
United States	Carilion Roanoke	Roanoke	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Methodist Main Hospital	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	Providence Sacred Heart	Spokane	Washington
United States	Mercy Hospital Springfield	Springfield	Ohio
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Baylor Scott & White - Temple	Temple	Texas
United States	Wellspan York Hospital	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Inari Medical

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Poland,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite clinical endpoint constructed as a win ratio, a hierarchy of the following, which are assessed post-randomization:	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	through discharge or 30 days, whichever is sooner / dyspnea at 48 hours
Secondary	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
Secondary	All-cause and PE-related mortality		At 30 and 90 days
Secondary	All-cause and PE-related readmissions		At 30 and 90 days
Secondary	Clinical deterioration	defined by hemodynamic or respiratory worsening	Through discharge or up to 30 days after randomization, whichever is sooner
Secondary	Bailout therapy	either after a deterioration or after documented failure to progress,	Through discharge or up to 30 days after randomization, whichever is sooner
Secondary	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
Secondary	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
Secondary	PE-related quality of life, by PEmb-QoL	Pulmonary Embolism Quality of Life: (higher = better)	At the 1- and 3-month visits
Secondary	General health-related quality of life, by EQ-5D-5L	Higher score = worse	At the 1- and 3-month visits
Secondary	6-minute walk distance		At the 1-month visit
Secondary	RV/LV ratio		At the 48-hour visit
Secondary	Post-PE Impairment diagnosis (PPEI)		Through the 3-month visit