Randomized Controlled Trial of Mechanical Thrombectomy Versus Catheter-directed Thrombolysis for Acute Hemodynamically Stable Pulmonary Embolism: Rationale and Design of the PEERLESS Study.

Abstract

BACKGROUND

The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the Pulmonary Embolism Response Team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and non-thrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients.

METHODS

The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a non-randomized MT cohort for separate analysis. The primary endpoint will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary endpoints. Other key secondary endpoints include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit.

IMPLICATIONS

PEERLESS is the first RCT to compare two different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted.