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

NCT07452991 | Recruiting

• 1 other identifier: 2024-09-10
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Embolism (PE)

Keywords

Pulmonary embolism; Ultrasound-assisted Catheter-guided Thrombolysis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (16)

• Pulmonary Embolism Severity Index (PESI) Score

  At admission; 48 hours post-procedure; Day 7 post-procedure or discharge (whichever occurs first)

• Right Ventricular to Left Ventricular (RV/LV) Ratio

  Baseline; 48 hours; Day 7/discharge

• Systolic Pulmonary Artery Pressure (sPAP)

  Baseline; 48 hours; Day 7/discharge

• Basal Right Ventricular Diameter (cm)

  Baseline; 48 hours; Day 7/discharge

• Tricuspid Annular Plane Systolic Excursion (TAPSE, cm)

  Baseline; 48 hours; Day 7/discharge

Study Arms (1)

Safety and clinical efficacy of EKOS in intermediate-high risk patients with PE

EXPERIMENTAL

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

Interventions

Ultrasound-assisted Catheter-guided Thrombolysis DEVICE

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.

Safety and clinical efficacy of EKOS in intermediate-high risk patients with PE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Presence of hemodynamic instability, defined as at least one of the following:
• Systolic blood pressure (SBP) \< 90 mmHg or a drop ≥ 40 mmHg from baseline for \> 15 minutes not attributable to arrhythmia, hypovolemia, or sepsis,
• Requirement for vasopressors to maintain SBP ≥ 90 mmHg,
• Cardiogenic shock, defined by clinical signs of end-organ hypoperfusion (e.g., altered mental status, oliguria, lactate elevation),
• Need for ECMO or other mechanical circulatory support initiated prior to assessment,
• 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;

Sponsors & Collaborators

• National Medical Research Center for Cardiology, Ministry of Health of Russian Federation: lead

Study Sites (1)

National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of the Ministry of Health of the Russian Federation

Moscow, Russia

RECRUITING

Related Publications (8)

• 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.

  PMID: 35588898 BACKGROUND

• 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.

  PMID: 37336568 BACKGROUND

• 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.

  PMID: 37855803 BACKGROUND

• 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.

  PMID: 37855802 BACKGROUND

• 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.

  PMID: 24226805 BACKGROUND

• 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.

  PMID: 32700589 BACKGROUND

• 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.

  PMID: 34560806 BACKGROUND

• 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.

  PMID: 31504429 BACKGROUND

MeSH Terms

Conditions

Pulmonary Embolism

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oleg Dorogun, MD

CONTACT

+7 919-764-2159; oleg.dorogun@gmail.com

Nikita Grishin, MD

CONTACT

+7 977-579-9185; n.s.grishin@mail.ru

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Emergency Cardiology Department

Model Details: 300 patients with intermediate-high risk pulmonary embolism (PE) and no contradictions for ultrasound-assisted catheter-guided thrombolysis will be enrolled. The risk of PE will be assessed by the institution's heart team. Patients participating in the clinical trial are expected to remain hospitalized for approximately 7-14 days and will be followed for 360 days (with an acceptable range of 350-370 days) after the intervention or until the occurrence of the primary endpoint.

Study Record Dates

• First Submitted: March 1, 2026
• First Posted: March 5, 2026
• Study Start: September 10, 2024
• Primary Completion (Estimated): September 10, 2029
• Study Completion (Estimated): September 10, 2030
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

RU (1)