Clinical trial NCT05111613: The PEERLESS Study
Official title: The PEERLESS Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Embolism
Pulmonary Thrombo-embolism
Keywords: PE
pulmonary embolism
thrombectomy
FlowTriever
CDT
Catheter-Directed Thrombolysis
Lead sponsor: Inari Medical
Sponsor class: INDUSTRY
First posted: 2021-11-08
Enrollment: 692
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria

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

Exclusion Criteria

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
* Patient unwilling or unable to conduct the follow up visits per protocol.

Primary outcomes:
measure: Composite clinical endpoint constructed as a win ratio, a hierarchy of the following:
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Secondary outcomes:
measure: Composite clinical endpoint constructed as a win ratio hierarchy of the following four components:
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: All-cause mortality
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: Intracranial hemorrhage (ICH)
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: Major bleeding per ISTH definition
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: ICU admission and ICU length of stay during the index hospitalization and following the index procedure
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: All cause mortality
timeFrame: 30 days from index procedure
measure: PE-related and all-cause readmission
timeFrame: 30 days from index procedure
measure: Device and drug-related serious adverse events
timeFrame: 30 days from index procedure
measure: Clinically Relevant Non-Major (CRNM) and Minor bleeding events
timeFrame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
measure: Change in right-ventricular/left-ventricular (RV/LV) ratio, as measured by echocardiography or CT
timeFrame: Baseline to 24 hour visit
measure: Modified Medical Research Council (mMRC) dyspnea score
timeFrame: At 24 hour and 30 day visits
measure: Length of total hospital stay and post-index-procedure hospital stay
timeFrame: To a maximum of 30 days
measure: Pulmonary Embolism Quality of Life (PEmb-QOL)
timeFrame: At 30 day visit
measure: EQ-5D-5L Quality of Life
timeFrame: At 30 day visit
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Orange
country: United States
facility: Providence St. Joseph Orange
state: California
city: Pasadena
country: United States
facility: Huntington Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Lakeland
country: United States
facility: Radiology and Imaging Associates
state: Florida
city: Miami
country: United States
facility: Baptist Health South Florida
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Elk Grove Village
country: United States
facility: Ascension Alexian Brothers Medical Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Hospital - Indianapolis
state: Indiana
city: Louisville
country: United States
facility: Norton Heralthcare
state: Kentucky
city: Boston
country: United States
facility: Brigham and Women&#39;s Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Ascension St. John Hospital
state: Michigan
city: St. Cloud
country: United States
facility: CentraCare St. Cloud Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Camden
country: United States
facility: Virtua Lourdes
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Bay Shore
country: United States
facility: Northwell Health
state: New York
city: Buffalo
country: United States
facility: Gates Vascular Institute
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian Columbia University Irving Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Health
state: North Carolina
city: Wilmington
country: United States
facility: Novant Health New Hanover Regional Medical Center
state: North Carolina
city: Akron
country: United States
facility: Summa Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Mercy Health West
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's University Hospital
state: Pennsylvania
city: Erie
country: United States
facility: AHN Saint Vincent Hospital
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Harrisburg
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Health University Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System
state: South Carolina
city: West Columbia
country: United States
facility: Lexington Medical Center
state: South Carolina
city: Nashville
country: United States
facility: HCA TriStar Centennial Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Ascension Saint Thomas Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: HCA Medical City Heart and Spine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Medical Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Main Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Appleton
country: United States
facility: Ascension St. Elizabeth Hospital
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Düsseldorf
country: Germany
facility: Universtitaetsklinikum Dusseldorf
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Wesel
country: Germany
facility: Marien Hospital Wesel GmbH
city: Bern
country: Switzerland
facility: Inselspital - Universitätsspital Bern
Study officials:
affiliation: Emory University
name: Wissam Jaber, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thomas Jefferson University
name: Carin Gonsalves, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bern University Hospital
name: Stefan Stortecky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.