Late Phase Clinical Trial Design and Planning for Pulmonary Embolism - Thrombus Removal with Adjunctive Catheter-Directed Therapy (PE-TRACT)

New York University School Of Medicine, New York NY

Investigators

Abstract

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 early deterioration, survivors suffer from reduced exercise capacity, shortness of breath, and a lower quality of life that persists long after the acute event. While systemic thrombolysis reduces deterioration from PE, this benefit is offset by substantial increases in major and intracranial bleeding. Catheter-directed thrombolysis (CDT), which dissolves pulmonary artery thrombus with a much lower dose of thrombolytic drug, appears to be efficacious in treating submassive PE with a lower risk of bleeding than systemic thrombolysis, based on preliminary studies. Consequently, CDT is often used in the U.S. to treat submassive PE. However, CDT has risk and is costly, and it has not yet been rigorously shown to improve short and long-term health. Therefore, we plan to conduct a large multicenter randomized-controlled study, the Pulmonary Embolism: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (PE-TRACT) trial, to determine if CDT should be used to treat submassive PE. Our central hypothesis is that submassive PE patients who receive CDT plus anticoagulation (CDT) will have better short-term and long-term health than those who receive anticoagulation alone (No-CDT). We have identified several key challenges to conducting PE-TRACT using a traditional trial design: 1) identifying the optimal primary outcome; 2) determining the best eligibility criteria; and 3) successfully recruiting patients into a medical vs. interventional therapy trial. Therefore, before conducting this phase 3 study, we seek to secure a U34 planning grant that: a) utilizes the NHLBI's Innovative Clinical Trials Resource (ICTR) and its Fixed and Adaptive Clinical Trials Simulator (FACTS) to help plan an efficient and innovative trial; and b) prepare for rapid start-up and enrollment (e.g., Institutional Review Board (IRB) approvals, monitoring plans; manuals of operation, data capture mechanisms). We offer the following specific aims: 1) Finalize a trial protocol in advance of an NHLBI grant application to conduct PE-TRACT; 2) Build a trial infrastructure to enable rapid start-up; and 3) Develop a patient recruitment strategy. We are confident that, after finalizing an efficient and innovative trial design with the ICTR and completing other essential planning activities, our expert team will be poised to successfully conduct PE-TRACT.