C-79 | Design and rationale for PEERLESS II, a multicenter, randomized controlled trial of large-bore thrombectomy versus anticoagulation alone in intermediate-risk pulmonary embolism

Anticoagulation (AC) is recommended for intermediate-risk pulmonary embolism (PE). However, reperfusion therapies may provide benefit over AC alone. PEERLESS II will assess outcomes in intermediate-risk PE patients randomized to treatment with FlowTriever large-bore mechanical thrombectomy and AC vs. AC alone. PEERLESS II is an international RCT enrolling up to 1,200 intermediate-risk PE patients with RV dysfunction and additional clinical risk factors from up to 100 sites. Treatment will be randomized 1:1 between two treatment arms: 1) large-bore mechanical thrombectomy with the FlowTriever System and AC or 2) AC alone. Efficacy and safety events will be adjudicated by an independent clinical events committee. The primary study endpoint is a composite win ratio that compares the following in order: 1) 30-day all-cause death, 2) clinical deterioration through discharge or 30 days, 3) 30-day all-cause hospital readmission, 4) bailout therapy through discharge or 30 days, and 5) 48-hour visit mMRC dyspnea score ≥ 1. Secondary endpoints include an evaluation of the first three components of the primary endpoint, each individual primary endpoint component, 30- and 90-day all-cause and PE-related death and readmission, 30- and 90-day major bleeding, 48-hour RV/LV ratio, 48-hour and 1- and 3-month mMRC dyspnea score, 1- and 3-month quality of life via PEmb-QoL and EQ-5D-5L, 1-month 6-minute walk distance, and post-PE impairment diagnosis through the 3-month visit. PEERLESS II will evaluate the optimal treatment for intermediate-risk PE and produce evidence for consideration in future treatment guidelines.