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Building an NIH-funded trial 

09-22-2022 01:33 PM

Inside the origin and design of PE-TRACT

Hope Racine and Jess Kirby | Fall 2022

When faced with an intermediate-risk pulmonary embolism, many physicians are increasingly turning to catheter-directed therapy (CDT). But is this the best course of action—especially when the patient’s long-term health is taken into account? According to Akhi Sista, MD, FSIR, existing data doesn’t provide a satisfactory answer.

The Pulmonary Embolism: Thrombus Removal with Adjunctive Catheter-directed Therapy (PE-TRACT) trial, designed by Dr. Sista and an experienced steering committee, incorporates adaptive design, simulation work and modern trial techniques to assess the efficacy and long-term impact of CDT plus anticoagulation on intermediate-risk PEs over anticoagulation alone. Dr. Sista has recently received funding from the National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI), which will support the enrollment of up to 500 patients to partake in a multicenter randomized controlled study. Patients will be assessed at 3 months, measuring peak oxygen consumption using cardiopulmonary exercise testing, and again at 1 year, using the New York Heart Association dyspnea class. The resulting data will not only examine the impact of CDT but also provide deeper insight into the biology of PEs.

Informing the PE community

“The first end goal is to give Level 1 data to the PE community to help them make decisions when they’re confronted with an acute PE patient who’s presenting with an immediate-risk PE,” said Dr. Sista.

The success of the PE response team (PERT) model has shown that the treatment of PE is a multidisciplinary effort that requires collaboration across specialties. As a result, Dr. Sista describes PE-TRACT as a PE community study, rather than an IR study. “There are many people keen to have this question addressed,” he said, citing pulmonologists, cardiologists, hematologists, vascular medicine physicians, hospitalists and emergency physicians, in addition to IRs and vascular surgeons. As with the PERT model, Dr. Sista hopes the PE-TRACT approach may be broadly applied to other interventions in which multiple disciplines need to collect data on established therapies.

Though so many specialties touch on PEs, they’re still relatively understudied, Dr. Sista said. There is a paucity of data and previous studies have either lacked randomization or provided insufficient hard clinical outcomes data. PE-TRACT is designed to not only meet rigorous scientific standards, but also to answer larger questions within the disease space.

“The second goal of PE-TRACT is to really understand the natural history of PE through a rigorous trial and to see if something we as IRs do relatively frequently can improve quality of life and functional capacity and exercise tolerance in the year following PE,” said Dr. Sista.

Designing an NIH-funded trial

Dr. Sista compared the potential impact of PE-TRACT to that of the ATTRACT trial, led by Suresh Vedantham, MD, FSIR, which provided substantial data on the nature of deep vein thrombosis, as well as patient selection for endovascular therapies.

The comparison is natural, as Dr. Sista worked closely with Dr. Vedantham on the ATTRACT trial. After designing an initial clinical trial protocol for investigating CDT for PE during a Radiological Society of North America workshop in 2014, Dr. Sista reached out to Dr. Vedantham for aid.

“Dr. Vedantham offered to bring the ATTRACT group together to consider the project,” Dr. Sista said, which he calls the “genesis” of the PE-TRACT trial. From there, Dr. Sista and fellow investigators applied to the NHLBI four times for funding before successfully obtaining a grant in summer 2022.

“Suresh told me to count on it being a longer project than expected,” Dr. Sista said. “I didn’t initially believe him. But once you’re down the path, you see that there’s another step ahead, something can be improved. There’s always an opportunity to continue the process, and by continuing you are striving for something that is so important for your specialty.”

The process was difficult, Dr. Sista said. Applications, which can be 450 pages long, require the work of 20–30 people, building a team within your institution, as well as advocating for the research to outside communities. Trials of this level also benefit from insight into current trends in industry. “You put together a research strategy,” Dr. Sista said, “then you develop a budget, a trial management plan and a steering committee. Then you ensure that committee is informed and actually believes you can pull it off.”

That’s where Dr. Vedantham’s mentorship was crucial, as well as his faith in Dr. Sista’s abilities. Dr. Vedantham has secured NIH funding before, so he was able to guide Dr. Sista through the process—and potential pitfalls.

“There’s a common misconception that if you write a perfect grant, you’ll get the funding,” Dr. Vedantham said. “You do need a perfect grant, but there’s a lot more beyond that. You have to think about the way in which you as a principal investigator interact with the NIH.”

According to Dr. Vedantham, within each institute of the NIH, like the NHLBI, project officers are tasked with reaching out to the community of physicians and scientists to find opportunities for the advancement of health. There are many ways in which they perform this outreach, but according to Dr. Vedantham, establishing yourself as a resource and leader in a space and connecting it to the work the NIH does may increase your likelihood of funding.

“I don’t believe Akhi would have been funded if the NIH didn’t appreciate, outside of his grant submission, that he had put in the requisite scholarship and had the kinds of accomplishments and experiences that demonstrate he has enough insight to run a multicenter study and understand the arena and the stakeholders,” Dr. Vedantham said.

Advocating for IR

A crucial takeaway, Dr. Vedantham said, is that the success of the PE-TRACT grant shows this kind of support is possible for interventional radiology.

“We don’t come up through training in the scientific knowledge of a particular disease process, so the way we get to NIH funding is different,” Dr. Vedantham said. “But my hope is that this trial may also provide insight into the ways in which an IR can become a research scientist and begin producing data to prove the value of our interventions.” A secondary benefit of the trial, Dr. Vedantham said, is proving to the NIH that IR can contribute rigorous researchers to the broader scientific community.

Dr. Sista also cites these benefits as a key outcome of the study.

“Not only can PE-TRACT put IR on the map as a serious specialty that cares about science and finding the truth, but we can hopefully also empower future IRs to undertake such questions and use the model and mentorship of Suresh and other IR leaders to conduct trials like ATTRACT, C-TRACT and PE-TRACT,” Dr. Sista said. "We want to encourage young and hungry investigators to research genicular artery embolization or prostate artery embolization or some of the other major interventions that IRs are known for, to really raise the bar for the type of evidence that needs to be generated for us to be taken seriously—not just within our society but beyond as well.”

NIH funding and support opens doors beyond research, Dr. Vedantham said. After receiving funding for ATTRACT, he was invited to participate in multiple government panels and large-scale initiatives within the broader medical community.

“The seat at the table came largely from the perception that there is a rigorous partner in IR,” he said. “I think Dr. Sista will experience the same thing. IR has longed to have an even larger footprint in the oversight and regulation of medicine, and one of the best and most effective ways is to be established as a credible and involved partner in care.”

How to join

PE-TRACT, and its potential impact, is a celebration of the field of IR, according to Dr. Sista—one he hopes other IRs will encourage and support.

Dr. Sista is actively looking for sites to enroll into PE-TRACT. Site investigators must believe in the questions being asked, be comfortable with randomization and have the facilities and resources for cardiopulmonary exercise testing. According to Dr. Sista, participating in PE-TRACT will be ideal for those interested in becoming involved in clinical research, have a passion for PE and want to develop a reputation in their community as a high-minded researcher. Dr. Sista hopes to have 40–50 sites enrolled by mid-2023, with enrollment completed within 3–4 years and data published by 2028–2029.

“There are very few investigator-initiated studies in the environment of PE care right now. So we need to champion this, celebrate it, prioritize it and ensure its success,” he said. “Not only because its success will cement IR’s place in high-minded research, but because it will also cement the idea that we can conduct NIH research and do so successfully."

For more information or to enroll your site in PE-TRACT, IRs are encouraged to email Dr. Sista at

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