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

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation300 enrolled

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.

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

Allocation

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

All-cause mortality

Total number of deaths from any cause.

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)

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

Time frame: 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. At day 360 of follow-up.

Secondary Outcomes

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.

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

Ratio measured by transthoracic echocardiography or computed tomography pulmonary angiography. Evaluates right ventricular pressure overload and recovery.