The PEERLESS II Study

Not Applicable

Recruiting

• Conditions: Pulmonary Embolism
• Interventions: Device: FlowTriever System; Drug: 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

Study Timeline

• Study First Submitted: 2023-09-15
• Study First Submitted QC: 2023-09-20
• Study First Posted: 2023-09-28
• Study Start: 2023-11-17
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-15
• Last Update Posted: 2025-07-18
• Primary Completion: 2026-07
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1200

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

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; * Change in Dyspnea, by mMRC from Baseline to 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 days
All-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 confirmation
Dyspnea 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 undressing
RV/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

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