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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• All-cause mortality [Time frame: 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) [Time frame: 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. At day 360 of follow-up.]

Secondary outcome measures (12)

• Pulmonary Embolism Severity Index (PESI) Score [Time frame: At admission; 48 hours post-procedure; Day 7 post-procedure or discharge (whichever occurs first)]
• Right Ventricular to Left Ventricular (RV/LV) Ratio [Time frame: Baseline; 48 hours; Day 7/discharge]
• Systolic Pulmonary Artery Pressure (sPAP) [Time frame: Baseline; 48 hours; Day 7/discharge]
• Basal Right Ventricular Diameter (cm) [Time frame: Baseline; 48 hours; Day 7/discharge]
• Tricuspid Annular Plane Systolic Excursion (TAPSE, cm) [Time frame: Baseline; 48 hours; Day 7/discharge]
• Inferior Vena Cava (IVC) Diameter and Collapsibility [Time frame: Baseline; 48 hours; Day 7/discharge]
• Number of participants with cardiogenic shock [Time frame: 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 [Time frame: At 48 hours post-procedure. At day 7 after PCI or at discharge, if earlier.]
• Number of patients requiring blood transfusion [Time frame: Within 48 hours; during hospitalization]
• Number of participants with stroke or transient ischemic attack [Time frame: 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier.]
• Intra-Procedural Mortality [Time frame: During procedure]
• Number of patients with Unsuccessful Catheter Placement [Time frame: During procedure]

Eligibility criteria

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:

• 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).

Exclusion criteria

• 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;
• Pregnancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Russia · 1 center

• National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of — Moscow

Publications

• 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- PMID 35588898
• 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
• 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
• 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
• 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: 10.1 PMID 24226805
• 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
• 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 Acut PMID 34560806
• 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 co PMID 31504429

Identifiers

NCT: NCT07452991 · 2024-09-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗