1/2 Pulmonary Embolism: Thrombus Removal with Catheter-Directed Therapy (PE-TRACT Trial)

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PROJECT SUMMARY The optimal management of patients with submassive pulmonary embolism (PE), who have right heart dysfunction but a normal blood pressure, is uncertain. In addition to being at risk for poor short-term outcomes, these patients suffer from reduced functional capacity and a 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, appears to be as effective as systemic thrombolytic therapy without substantially increasing bleeding. Consequently, CDT is often used in the U.S. to treat submassive PE. However, CDT has risk and is costly, and it is not known if it improves cardiopulmonary heath, particularly over the long-term. We therefore plan to do 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 500 patients with submassive PE. We will use an "adaptive sample size" which could result in enrollment being stopped 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 NYHA class at 12 months (long-term). These will be 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. Secondary outcomes include generic quality of life (QOL) (SF- 36), 6-minute walk distance, clinical deterioration from PE, and cost-effectiveness. Exploratory analyses will assess: disease-specific QOL, other cardiopulmonary exercise test parameters, recurrent venous thromboembolism and complications of the CDT procedure. Predictors of therapeutic response will also be sought. 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.