Clinical trial NCT06055920: The PEERLESS II Study
Official title: PEERLESS II: RCT of FlowTriever vs. Anticoagulation Alone in Pulmonary Embolism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pulmonary Embolism
Lead sponsor: Inari Medical
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 1200
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: This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System plus anticoagulation compared to anticoagulation alone for intermediate-risk acute PE.


Eligibility criteria: 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

Primary outcomes:
measure: Composite clinical endpoint constructed as a win ratio, a hierarchy of the following, which are assessed post-randomization:
timeFrame: through discharge or 30 days, whichever is sooner / dyspnea at 48 hours
Secondary outcomes:
measure: Composite clinical endpoint constructed as a win ratio hierarchy of the following three components, assessed post randomization:
timeFrame: up to 30 days
measure: All-cause and PE-related mortality
timeFrame: At 30 and 90 days
measure: All-cause and PE-related readmissions
timeFrame: At 30 and 90 days
measure: Clinical deterioration
timeFrame: Through discharge or up to 30 days after randomization, whichever is sooner
measure: Bailout therapy
timeFrame: Through discharge or up to 30 days after randomization, whichever is sooner
measure: Major Bleeding, defined by the Bleeding Academic Research Consortium (BARC), level 3b, 3c, 5a, or 5b
timeFrame: At 30 and 90 days
measure: Dyspnea severity by mMRC score
timeFrame: At the 48-hour, 1-month, and 3-month visits
measure: PE-related quality of life, by PEmb-QoL
timeFrame: At the 1- and 3-month visits
measure: General health-related quality of life, by EQ-5D-5L
timeFrame: At the 1- and 3-month visits
measure: 6-minute walk distance
timeFrame: At the 1-month visit
measure: RV/LV ratio
timeFrame: At the 48-hour visit
measure: Post-PE Impairment diagnosis (PPEI)
timeFrame: Through the 3-month visit
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Division of Cardiovascular Disease
state: Alabama
city: Birmingham
country: United States
facility: Brookwood Medical Center
state: Alabama
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Largo
country: United States
facility: HCA FL Largo Medical Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Lansing
country: United States
facility: McLaren Greater Lansing
state: Michigan
city: Coon Rapids
country: United States
facility: Metropolitan Heart & Vascular Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: Virtua Health
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Health
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: SUNY, The University of Buffalo/Gates Vascular
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Queens
country: United States
facility: Jamaica Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University - Wexner Medical Center
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: Erie
country: United States
facility: UPMC Hamot
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Harrisburg
state: Pennsylvania
city: Philadelphia
country: United States
facility: The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network Research Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Heart and Vascular Institute
state: Pennsylvania
city: York
country: United States
facility: Wellspan York Hospital
state: Pennsylvania
city: Brentwood
country: United States
facility: HCA Tristar
state: Tennessee
city: Knoxville
country: United States
facility: UTMC Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Ascension Saint Thomas Hospital
state: Tennessee
city: Dallas
country: United States
facility: Parkland Hospital
state: Texas
city: Fort Worth
country: United States
facility: Texas Health Harris Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Main Hospital
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White - Temple
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax
state: Virginia
city: Norfolk
country: United States
facility: Sentara Vascular Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart
state: Washington
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Ruby Memorial Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Aalst
country: Belgium
facility: Onze Lieve Vrouwziekenhuis
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Surrey
country: Canada
facility: Surrey Memorial Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Hôpital Louis Pradel
city: Marseille
country: France
facility: AP-HM Hopital La Timone
city: Marseille
country: France
facility: Hôpital Nord Marseille
city: Augsburg
country: Germany
facility: University Hospital Augsburg
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Bad Krozingen
city: Berlin
country: Germany
facility: Charité Campus Virchow Clinic - Klinik fuer Radiologie
city: Berlin
country: Germany
facility: Unfall Krankenhaus Berlin
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Dresden
country: Germany
facility: HerzZentrum Dresden Universitaetsklinik
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Dὒsseldorf
city: Essen
country: Germany
facility: Elisabeth Hospital GmbH
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: CCB Frankfurt
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital - Heidelberg
city: Homburg
country: Germany
facility: Universitaetsklinikum Saarlandes Homburg
city: Kaiserslautern
country: Germany
facility: Westpfalz Klinikum
city: Munich
country: Germany
facility: Klinikum rechts der Isar (TUM)
city: Munich
country: Germany
facility: Ludwig Maximilians-University
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar-Klinikum
city: Kraków
country: Poland
facility: John Paul II Hospital
city: Madrid
country: Spain
facility: Hopital Clinico Universitario San Carlos
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Bern
country: Switzerland
facility: Universitätsspital Bern
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
Study officials:
affiliation: Jefferson Health,
name: Frances Mae West, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn Medicine
name: Jay Giri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité University Hospital Berlin
name: Bernhard Gebauer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaetsspital Basel
name: Felix Mahfoud, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.