PEERLESS II: A Randomized Controlled Trial of Large-Bore Thrombectomy Versus Anticoagulation in Intermediate-Risk Pulmonary Embolism.

Background: Anticoagulation (AC) is the guideline-recommended treatment for intermediate-risk pulmonary embolism (PE); however, it remains unclear whether mechanical thrombectomy provides benefit over AC alone. The PEERLESS II study aims to evaluate outcomes in intermediate-risk PE patients randomized to treatment with large-bore mechanical thrombectomy and AC vs AC alone. Methods: PEERLESS II is an international randomized controlled trial enrolling up to 1200 patients with intermediate-risk PE and additional clinical risk factors from up to 100 sites. Treatment is randomized 1:1 to large-bore mechanical thrombectomy with the FlowTriever System (Inari Medical) and AC or AC alone. Outcomes will be evaluated for up to 3 months, with safety events independently adjudicated. The primary end point is a hierarchical composite win ratio of (1) all-cause mortality by 30 days, (2) clinical deterioration (earlier of discharge or 30 days), (3) all-cause hospital readmission by 30 days, (4) bailout therapy (earlier of discharge or 30 days), and (5) Modified Medical Research Council (mMRC) dyspnea score of ≥1 at the 48-hour visit. Secondary end points include all-cause and PE-related mortality (30-day and 90-day), all-cause and PE-related readmission (30-day and 90-day), major bleeding (30-day and 90-day), clinical deterioration (earlier of discharge or 30 days), bailout (earlier of discharge or 30 days), right ventricle-to-left ventricle diameter ratio (48-hour visit), mMRC dyspnea score (48-hour, 1-month, and 3-month visits), quality of life using Pulmonary Embolism Quality of Life and EuroQol-5 Dimensions-5 Levels (1-month and 3-month visits), 6-minute walk distance (1-month visit), and post-PE impairment diagnosis (3-month visit). Conclusions: PEERLESS II will inform the understanding of mechanical thrombectomy treatment for intermediate-risk PE and provide evidence for consideration in future treatment guidelines.