4 Trials That May Change Pulmonary Embolism, with Parth Rali, MD

It has been more than a decade since the PEITHO trial showed fibrinolytic therapy tenecteplase plus heparin more greatly prevented hemodynamic decompensation in patients with intermediate-risk pulmonary embolism (PE). It was also that year, in 2014, when investigators investigators found standardized ultrasound-assisted catheter-directed thrombolysis (USAT) was superior to lone anticoagulation in reversal of right ventricular dilatation in patients with intermediate-risk PE.

In those 10 years, there has been a dearth of novel clinical trial insights into treating intermediate-risk PE, explained Parth Rali, MD. But that trend will quickly change.

In an interview with HCPLive during the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago, IL, Rali, director of the Temple University Health System Pulmonary Embolism Response Team (PERT) Program, reviewed a handful of randomized clinical trials rolling out data or just kicking off since 2024 that will likely influence PE intervention strategies.

“I think we are at the right time, for the right reasons, [to treat] our patients,” Rali said.

Here are 4 randomized, controlled trials Rali highlighted for their potential impact to PE intervention.

PEITHO-3

The study intends to enroll 650 patients with acute intermediate-high-risk PE, to assess reduced-dose intravenous tissue plasminogen activator (tPA) alteplase compared to standard anticoagulant therapy in all-cause death, hemodynamic decompensation, or PE recurrence ≤30 days post-randomization. Rali noted the trial has surpassed the mid-mark of enrollment.

“We are looking at a reduced dose, or a weight-based dose — which we have never studied in the PE space before,” Rali said. “I think that is exciting, because that’s more real-world, more evidence-based, and I think it’s going to decide which group of patients would benefit from tPA in the PE space.”

HI-PEITHO

The multinational assessment aims to establish first-line treatment in patients with intermediate-high-risk PE and imminent hemodynamic collapse. Patients with confirmed acute PE, evidence of right ventricular dysfunction per imaging, a positive cardiac troponin test, and clinical criteria indicating elevated risk of early death or imminent hemodynamic collapise will be randomized 1:1 to either ultrasound-facilitated catheter-directed thrombolysis plus anticoagulants or lone anticoagulants.

STORM-PE

Rali said updates from the trial assessing catheter-directed thrombectomy from a penumbra device versus anticoagulation in patients with PE will likely be presented at the Transcatheter Cardiovascular Therapeutics (TCT) Annual Symposium in late October.

PEERLESS II

Investigating large-bore thrombectomy versus anticoagulation in patients with intermediate-risk PE, this international trial plans to enroll ≤1200 patients across 100 sites — one of the largest randomized, controlled trials the field has seen, Rali said.

Is this a new era for PE trials?

Rali additionally highlighted the PE-TRACT trial, an open-label investigation funded by the National Institutes of Health (NIH) assessing anticoagulation versus any form of catheter-directed therapy. The trial is unique two-fold: it is not industry0funded, and it will prioritize long-term, patient-reported outcomes similarly to immediate clinical outcomes.

“It’s kind of a nice balance of industry-funded and non-industry-funded trials looking at these similar populations and similar outcomes across US and European sites,” Rali said.

The output of data from these upcoming trials will practically triple the amount of interpretable patient outcomes for intermediate PE, Rali estimated — moving the observed population from approximately 1800 total randomized patients, to about 5300,

“We are looking at the randomized patients with intermediate-risk PE totaling around 5000 to 6000 in next couple of years, which I think is great for our patient care,” Rali said. “That means lot of work needs to be done toward how to interpret those trials, but I think it's exciting for the field.”

References

1. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411. doi:10.1056/NEJMoa1302097
2. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479-486. doi:10.1161/CIRCULATIONAHA.113.005544
3. Sanchez O, Charles-Nelson A, Ageno W, et al. Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial. Thromb Haemost. 2022;122(5):857-866. doi:10.1055/a-1653-4699
4. Klok FA, Piazza G, Sharp ASP, et al. Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study. Am Heart J. 2022;251:43-53. doi:10.1016/j.ahj.2022.05.011
5. Rosovsky RP, Konstantinides SV, Moriarty JM, et al. A prospective, multicenter, randomized controlled trial evaluating anticoagulation alone vs anticoagulation plus computer assisted vacuum thrombectomy for the treatment of intermediate-high-risk acute pulmonary embolism: Rationale and design of the STORM-PE study. Am Heart J. 2025;288:1-14. doi:10.1016/j.ahj.2025.03.018
6. Giri, Jay et al. PEERLESS II: A Randomized Controlled Trial of Large-Bore Thrombectomy Versus Anticoagulation in Intermediate-Risk Pulmonary Embolism. Journal of the Society for Cardiovascular Angiography & Interventions, Volume 3, Issue 6, 101982.
7. Sista AK, Troxel AB, Tarpey T, et al. Rationale and design of the PE-TRACT trial: A multicenter randomized trial to evaluate catheter-directed therapy for the treatment of intermediate-risk pulmonary embolism. Am Heart J. 2025;281:112-122. doi:10.1016/j.ahj.2024.11.016