ULTRAsound-assisted Catheter-guided Thrombolysis for Intermediate-high Risk Patients With PE (ULTRA-PE)

ULTRAsound-assisted Catheter-guided Thrombolysis for Intermediate-high Risk Patients With Pulmonary Embolism

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of cardiovascular mortality. While systemic thrombolysis is the standard treatment for high-risk PE, its bleeding risk limits use in some patients, highlighting the need for alternative reperfusion strategies such as catheter-directed thrombolysis (CDT). This prospective study will evaluate the safety and efficacy of CDT using the EkoSonic Endovascular System (EKOS; Boston Scientific) in patients with intermediate-high and high-risk PE. The primary outcome is all-cause mortality through 360 days of follow-up, with secondary outcomes including changes in echocardiographic parameters such as the RV/LV diameter ratio.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Embolism (PE)
• Intervention / Treatment: Device: Ultrasound-assisted Catheter-guided Thrombolysis

Detailed Description

Pulmonary embolism (PE) is an acute, life-threatening condition, ranking as the third leading cause of mortality from cardiovascular diseases worldwide. The main approach for treating high-risk PE is systemic thrombolysis, however due to the associated risk of major hemorrhage, its use is contraindicated in certain patient populations, underscoring the need for alternative reperfusion strategies.

In recent years, catheter-directed thrombolysis (CDT) have been increasingly used in the treatment of PE due to a number of advantages including shorter infusion duration, lower doses of thrombolytic drugs leading to a more rapid achievement of therapeutic effect. Among all CDT, the most cost-effective are in situ and ultrasound-assisted thrombolysis, with only the latter being available in the Russian Federation. This prospective study will include patients with intermediate-high and high-risk PE treated with CDT, specifically EkoSonic Endovascular System (EKOS; Boston Scientific). The findings of this study will add to the current body of evidence regarding the management and outcomes of patients with acute intermediate-high risk PE, and will provide controlled data on CDT approaches.

The primary outcome will include all-cause mortality at day 7 after procedure or at discharge, if earlier, to day 360 of follow-up. The secondary outcome will include echocardiographic parameters, e.g. the change in RV/LV diameter ratio from baseline to first outpatient follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Oleg Dorogun, MD; Phone Number: +7 919-764-2159; Email: oleg.dorogun@gmail.com
• Study Contact Backup: Name: Nikita Grishin, MD; Phone Number: +7 977-579-9185; Email: n.s.grishin@mail.ru

Study Locations

• Russia
  • Moscow, Russia
    • Recruiting
    • National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of the Ministry of Health of the Russian Federation
    • Contact: Ilia Zyuryaev; Phone Number: +7-903-260-49-72; Email: zyuryaev@list.ru
    • Contact: Nikita Grishin; Phone Number: +7-977-579-9185; Email: n.s.grishin@mail.ru
    • Sub-Investigator: Andrey Tereshchenko, MD, PhD
    • Sub-Investigator: Goar Arutiunian, MD, PhD
    • Sub-Investigator: Ivan Zharovin, MD
    • Sub-Investigator: Elizaveta Krasnoperova, MD
    • Sub-Investigator: Irina Merkulova, MD
    • Sub-Investigator: Zuliana Bashankaeva, MD
    • Sub-Investigator: Andrey Levshukov, MD
    • Sub-Investigator: Diana Khummedova, MD
    • Sub-Investigator: Nikolay Germanov, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged ≥ 18 years at time of enrollment;
• Ability to provide written informed consent (or legally authorized representative consent where applicable);
• Objectively confirmed acute pulmonary embolism (PE) by contrast-enhanced computed tomography pulmonary angiography (CTPA) demonstrating intraluminal filling defects in at least one segmental, lobar, or more proximal pulmonary artery;
• Hemodynamically stable at presentation (i.e., not meeting high-risk PE criteria of sustained hypotension, shock, or need for vasopressor support per ESC 2019 and AHA/ACC risk stratification);
• Evidence of right ventricular (RV) dysfunction on imaging (e.g., RV/LV ratio > 1.0 on CTPA or echocardiography);
• Elevated cardiac biomarkers, including troponin I or T above the upper limit of normal;
• Intermediate-high risk features defined as the combination of imaging RV dysfunction and positive cardiac biomarkers, consistent with ESC stratification;

• At least one clinical indicator of elevated early risk such as:

  1. Tachycardia (e.g., HR ≥ 100 bpm),
  2. Mild systolic blood pressure reduction (e.g., SBP ≤ 110 mmHg but not meeting high-risk thresholds),
  3. Hypoxemia (SpO₂ < 90% on room air).

Exclusion Criteria:

• Presence of hemodynamic instability, defined as at least one of the following:

  1. Systolic blood pressure (SBP) < 90 mmHg or a drop ≥ 40 mmHg from baseline for > 15 minutes not attributable to arrhythmia, hypovolemia, or sepsis,
  2. Requirement for vasopressors to maintain SBP ≥ 90 mmHg,
  3. Cardiogenic shock, defined by clinical signs of end-organ hypoperfusion (e.g., altered mental status, oliguria, lactate elevation),
  4. Need for ECMO or other mechanical circulatory support initiated prior to assessment,
  5. Cardiac arrest requiring resuscitation.
• Active major bleeding or conditions with high bleeding risk (e.g., known intracranial pathology predisposed to hemorrhage or associated with ongoing pharmacotherapy);
• Recent (< 3 months) intracranial or intraspinal surgery, major trauma, or stroke;
• Known central nervous system neoplasm or metastatic cancer with high bleed risk.
• Administration of systemic thrombolytic agents or catheter-directed thrombolysis prior to registry assessment for the index PE episode;
• Known hypersensitivity to alteplase, unfractionated heparin (UFH), or any of their excipients.
• Requirement for intensive care admission for conditions unrelated to the index PE;
• Duration of symptoms attributable to the index PE > 14 days at presentation, as defined in contemporary trial criteria;
• Known severe thrombocytopenia (e.g., platelet count < 100 × 10⁹/L) or coagulopathy precluding safe catheter access;
• Life expectancy < 6 months due to advanced comorbid disease unrelated to acute PE;
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Safety and clinical efficacy of EKOS in intermediate-high risk patients with PE; A total of 300 patients with intermediate-high risk pulmonary embolism (PE) and no contraindications to ultrasound-assisted catheter-directed thrombolysis will be enrolled. All enrolled patients will undergo thrombolytic therapy using the EkoSonic™ Endovascular System, which provides ultrasound-facilitated catheter-directed delivery of a thrombolytic agent. The total thrombolytic dose and dosing regimen will be determined by the institutional heart team.

Device: Ultrasound-assisted Catheter-guided Thrombolysis; The goal of the ULTRA-PE trial is to investigate the safety and clinical efficacy of ultrasound-assisted catheter-guided thrombolysis in intermediate-high risk patients with pulmonary embolism (PE) in Russia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Total number of deaths from any cause.	48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. At day 360 of follow-up.
Net Adverse Clinical Events (NACE)	Composite endpoint reflecting net clinical benefit, including: all-cause mortality; hemodynamic decompensation (vasopressor initiation, mechanical ventilation, cardiac arrest, escalation to systemic thrombolysis or surgical embolectomy); major bleeding (BARC 3-5 or ISTH major bleeding); intracranial hemorrhage	48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. At day 360 of follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right Ventricular to Left Ventricular (RV/LV) Ratio	Ratio measured by transthoracic echocardiography or computed tomography pulmonary angiography. Evaluates right ventricular pressure overload and recovery.	Baseline; 48 hours; Day 7/discharge
Systolic Pulmonary Artery Pressure (sPAP)	Measured by transthoracic echocardiography, estimated from tricuspid regurgitation velocity. Reflects pulmonary hypertension severity.	Baseline; 48 hours; Day 7/discharge
Basal Right Ventricular Diameter (cm)	Measured by transthoracic echocardiography	Baseline; 48 hours; Day 7/discharge
Tricuspid Annular Plane Systolic Excursion (TAPSE, cm)	Measured by transthoracic echocardiography	Baseline; 48 hours; Day 7/discharge
Inferior Vena Cava (IVC) Diameter and Collapsibility	Measured by transthoracic echocardiography	Baseline; 48 hours; Day 7/discharge
Number of participants with cardiogenic shock	As defined by SCAI-CSWG 2022	From the beginning of the procedure until its conclusion. Within 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier.
Number of participants with major bleeding	Major bleeding (BARC 3 to 5) after procedure, according to the BARC Bleeding Classification 2011.	At 48 hours post-procedure. At day 7 after PCI or at discharge, if earlier.
Number of patients requiring blood transfusion	Any transfusion of packed red blood cells.	Within 48 hours; during hospitalization
Number of participants with stroke or transient ischemic attack	As per VARC 2 definitions 2013.	48 hours post-procedure. At day 7 after procedure or at discharge, if earlier.
Intra-Procedural Mortality	Death occurring during catheter-directed thrombolysis.	During procedure
Number of patients with Unsuccessful Catheter Placement	Failure to achieve proper catheter positioning or device deployment.	During procedure
Number of patients with acute kidney injury (AKI)	Defined according to KDIGO criteria.	Within 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier.
Number of patients requiring cardiopulmonary resuscitation		During procedure. 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier.
Recurrent Pulmonary Embolism	Nonfatal symptomatic and objectively confirmed recurrence of PE	At day 360 of follow-up.
Development of Chronic Thromboembolic Pulmonary Hypertension	Chronic thromboembolic pulmonary hypertension will be confirmed at the investigational site if all of the following criteria are fulfilled: Presence of at least one mismatched segmental perfusion defect identified on ventilation/perfusion (V/Q) scintigraphy following a minimum of 3 months of adequate therapeutic anticoagulation.; Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg, as determined by invasive right heart catheterization.; Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg.	At day 360 of follow-up.
Pulmonary Embolism Severity Index (PESI) Score	Assessment of clinical risk stratification using the validated PESI score (Pulmonary Embolism Severity Index, values from 0 till 130+, the lower the better). Both absolute score and change from baseline will be analyzed, including transition between risk classes.	At admission; 48 hours post-procedure; Day 7 post-procedure or discharge (whichever occurs first)

Collaborators and Investigators

• Sponsor: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• Investigators: Principal Investigator: Dmitry Pevzner, MD, D.Sc., National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of the Ministry of Health of the Russian Federation; Principal Investigator: Evgeniy Merkulov, MD, D.Sc., National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of the Ministry of Health of the Russian Federation

Publications and helpful links

General Publications

• Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.
• Klok FA, Piazza G, Sharp ASP, Ni Ainle F, Jaff MR, Chauhan N, Patel B, Barco S, Goldhaber SZ, Kucher N, Lang IM, Schmidtmann I, Sterling KM, Becker D, Martin N, Rosenfield K, Konstantinides SV. 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 Sep;251:43-53. doi: 10.1016/j.ahj.2022.05.011. Epub 2022 May 16.
• Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ni Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. No abstract available.
• Sanchez O, Charles-Nelson A, Ageno W, Barco S, Binder H, Chatellier G, Duerschmied D, Empen K, Ferreira M, Girard P, Huisman MV, Jimenez D, Katsahian S, Kozak M, Lankeit M, Meneveau N, Pruszczyk P, Petris A, Righini M, Rosenkranz S, Schellong S, Stefanovic B, Verhamme P, de Wit K, Vicaut E, Zirlik A, Konstantinides SV, Meyer G; PEITHO-3 Investigators. 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 May;122(5):857-866. doi: 10.1055/a-1653-4699. Epub 2021 Oct 31.
• Planer D, Yanko S, Matok I, Paltiel O, Zmiro R, Rotshild V, Amir O, Elbaz-Greener G, Raccah BH. Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis. CMAJ. 2023 Jun 19;195(24):E833-E843. doi: 10.1503/cmaj.220960.
• Tefera L, Ziada KM, Cameron SJ. Pulmonary Embolism Unplugged: Catheter-Directed Therapies for Intermediate-Risk Pulmonary Embolism. JACC Cardiovasc Interv. 2023 Nov 13;16(21):2652-2654. doi: 10.1016/j.jcin.2023.08.029. Epub 2023 Oct 18. No abstract available.
• Zhang RS, Maqsood MH, Sharp ASP, Postelnicu R, Sethi SS, Greco A, Alviar C, Bangalore S. Efficacy and Safety of Anticoagulation, Catheter-Directed Thrombolysis, or Systemic Thrombolysis in Acute Pulmonary Embolism. JACC Cardiovasc Interv. 2023 Nov 13;16(21):2644-2651. doi: 10.1016/j.jcin.2023.07.042. Epub 2023 Oct 18.
• Hobohm L, Keller K, Munzel T, Gori T, Konstantinides SV. EkoSonic(R) endovascular system and other catheter-directed treatment reperfusion strategies for acute pulmonary embolism: overview of efficacy and safety outcomes. Expert Rev Med Devices. 2020 Aug;17(8):739-749. doi: 10.1080/17434440.2020.1796632. Epub 2020 Jul 29.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Estimated): September 10, 2029
• Study Completion (Estimated): September 10, 2030

Study Registration Dates

• First Submitted: March 1, 2026
• First Submitted That Met QC Criteria: March 1, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary embolism; Ultrasound-assisted Catheter-guided Thrombolysis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 2024-09-10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No