2/2 Pulmonary Embolism: Thrombus Removal with Catheter-Directed Therapy (PE-TRACT Trial) –DCC - PROJECT SUMMARY The optimal management of patients with submassive pulmonary embolism (PE), who have right heart dysfunction but a normal blood pressure, is uncertain. These patients are at risk for poor short-term outcomes, suffer from reduced functional capacity, and have lower quality of life over the long term. While systemic thrombolysis reduces clinical deterioration from PE, this benefit is offset by substantial increases in major and intracranial bleeding. Catheter-directed therapy (CDT), which dissolves pulmonary artery thrombus with a much lower dose of thrombolytic drug, may be as effective as systemic thrombolytic therapy without substantially increasing bleeding, but it has risks and is costly, and it is not known if it improves cardiopulmonary heath, particularly over the long term. We therefore plan to conduct an open-label, assessor-blinded, randomized trial, the Pulmonary Embolism: Thrombus Removal with Catheter-Directed Therapy (PE-TRACT) Study, to compare CDT with No-CDT in up to 500 patients with submassive PE. The trial is adaptive, and could result in enrollment being stopped early for superior efficacy or for futility at an interim analysis. There will be two primary efficacy outcomes: peak oxygen consumption at 3 months (short-term) and New York Heart Association (NYHA) class at 12 months (long-term), analyzed sequentially using a gatekeeping approach; for NYHA class to be compared, peak oxygen consumption must first be shown to be increased by CDT (P<0.05). The primary safety outcome will be major bleeding within 30 days of randomization. The Data Coordinating Center, led by experts with deep experience in adaptive and pragmatic clinical trial design and implementation, will oversee all aspects of study design, implementation, and analysis, and will provide state-of-the-art data collection and quality control infrastructure, reporting to the independent Data and Safety Monitoring Board, and provision of data and resources to the public. The PE-TRACT Study will change clinical practice: if CDT is effective and safe, it will become part of standard therapy for patients with submassive PE; if not, a risky and costly therapy will be avoided. Hence, either study outcome will improve public health and advance the NHLBI’s mission
