The PEERLESS Study

Study Overview
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Brief Summary
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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.

Official Title
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The PEERLESS Study

Conditions
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Pulmonary Embolism, Pulmonary Thrombo-embolism

Intervention / Treatment
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* Device: Catheter-Directed Thrombolysis
* Device: FlowTriever System


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Randomized Controlled Trial Cohort - FlowTriever Arm<br>Mechanical thrombectomy for pulmonary embolism using the FlowTriever System. | Device: FlowTriever System<br>* Mechanical thrombectomy for pulmonary embolism<br>|
| Active Comparator: Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm<br>Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system) | Device: Catheter-Directed Thrombolysis<br>* Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system)<br>|
| Other: Non-Randomized Absolute Contraindication to Thrombolytics Cohort<br>Mechanical thrombectomy for pulmonary embolism using the FlowTriever System. | Device: FlowTriever System<br>* Mechanical thrombectomy for pulmonary embolism<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite clinical endpoint constructed as a win ratio, a hierarchy of the following: | All-cause mortality, or Intracranial hemorrhage (ICH), or Major bleeding per ISTH definition, or Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy, or ICU admission and ICU length-of-stay during the index hospitalization and following the index procedure. | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite clinical endpoint constructed as a win ratio hierarchy of the following four components: | All-cause mortality, or Intracranial hemorrhage (ICH), or Major bleeding per ISTH definition, or Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| All-cause mortality |  | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| Intracranial hemorrhage (ICH) |  | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| Major bleeding per ISTH definition |  | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy |  | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| ICU admission and ICU length of stay during the index hospitalization and following the index procedure |  | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| All cause mortality |  | 30 days from index procedure | 
| PE-related and all-cause readmission |  | 30 days from index procedure | 
| Device and drug-related serious adverse events |  | 30 days from index procedure | 
| Clinically Relevant Non-Major (CRNM) and Minor bleeding events |  | Hospital discharge or at 7 days after the index procedure, whichever is sooner | 
| Change in right-ventricular/left-ventricular (RV/LV) ratio, as measured by echocardiography or CT |  | Baseline to 24 hour visit | 
| Modified Medical Research Council (mMRC) dyspnea score | The range of scores is zero to four (worse) | At 24 hour and 30 day visits | 
| Length of total hospital stay and post-index-procedure hospital stay |  | To a maximum of 30 days | 
| Pulmonary Embolism Quality of Life (PEmb-QOL) |  | At 30 day visit | 
| EQ-5D-5L Quality of Life |  | At 30 day visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PE, pulmonary embolism, thrombectomy, FlowTriever, CDT, Catheter-Directed Thrombolysis