Pulmonary Embolism (PE)
Conditions
Keywords
Pulmonary embolism, Ultrasound-assisted Catheter-guided Thrombolysis
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.
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
DEVICEUltrasound-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.
Sponsors
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. At day 360 of follow-up. | Total number of deaths from any cause. |
| Net Adverse Clinical Events (NACE) | 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. At day 360 of follow-up. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Embolism Severity Index (PESI) Score | At admission; 48 hours post-procedure; Day 7 post-procedure or discharge (whichever occurs first) | 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. |
| Right Ventricular to Left Ventricular (RV/LV) Ratio | Baseline; 48 hours; Day 7/discharge | Ratio measured by transthoracic echocardiography or computed tomography pulmonary angiography. Evaluates right ventricular pressure overload and recovery. |
| Systolic Pulmonary Artery Pressure (sPAP) | Baseline; 48 hours; Day 7/discharge | Measured by transthoracic echocardiography, estimated from tricuspid regurgitation velocity. Reflects pulmonary hypertension severity. |
| Basal Right Ventricular Diameter (cm) | Baseline; 48 hours; Day 7/discharge | Measured by transthoracic echocardiography |
| Tricuspid Annular Plane Systolic Excursion (TAPSE, cm) | Baseline; 48 hours; Day 7/discharge | Measured by transthoracic echocardiography |
| Inferior Vena Cava (IVC) Diameter and Collapsibility | Baseline; 48 hours; Day 7/discharge | Measured by transthoracic echocardiography |
| Number of participants with cardiogenic shock | From the beginning of the procedure until its conclusion. Within 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. | As defined by SCAI-CSWG 2022 |
| Number of participants with major bleeding | At 48 hours post-procedure. At day 7 after PCI or at discharge, if earlier. | Major bleeding (BARC 3 to 5) after procedure, according to the BARC Bleeding Classification 2011. |
| Number of patients requiring blood transfusion | Within 48 hours; during hospitalization | Any transfusion of packed red blood cells. |
| Number of participants with stroke or transient ischemic attack | 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. | As per VARC 2 definitions 2013. |
| Intra-Procedural Mortality | During procedure | Death occurring during catheter-directed thrombolysis. |
| Number of patients with Unsuccessful Catheter Placement | During procedure | Failure to achieve proper catheter positioning or device deployment. |
| Number of patients with acute kidney injury (AKI) | Within 48 hours post-procedure. At day 7 after procedure or at discharge, if earlier. | Defined according to KDIGO criteria. |
| 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 | At day 360 of follow-up. | Nonfatal symptomatic and objectively confirmed recurrence of PE |
| Development of Chronic Thromboembolic Pulmonary Hypertension | At day 360 of follow-up. | 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. |
Countries
Russia
Contacts
CONTACTOleg Dorogun, MD
CONTACTNikita Grishin, MD
PRINCIPAL_INVESTIGATORDmitry 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_INVESTIGATOREvgeniy Merkulov, MD, D.Sc.
National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of the Ministry of Health of the Russian Federation
Outcome results
None listed