Ultrasound-assisted, Catheter-directed Thrombolysis for Acute Intermediate-high-risk Pulmonary Embolism (USAT IH-PE)

Ultrasound-assisted, Catheter-directed Thrombolysis for Acute Intermediate-high-risk Pulmonary Embolism (USAT IH-PE): Impact on Short- and Long-term Outcome, a Multi-center Experience. An Observational Retrospective and Prospective Multi-center Study

The purpose of this retrospective and prospective multicenter study is to evaluate the incidence of pulmonary hypertension (PH) within 6 months from ultrasound-assisted, Catheter-directed Thrombolysis for acute intermediate- high-risk Pulmonary Embolism

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Procedure: ultrasound-assisted, catheter-directed thrombolysis

Detailed Description

Acute pulmonary embolism (PE) is a potentially life-threatening disease spanning a wide spectrum of clinical outcomes. PE is the third most common cardiovascular disorder in Europe and USA and causes an estimated 150,000 to 200,000 deaths.

In the latest 2019 European Society of Cardiology (ESC) Guidelines patients diagnosed with PE are stratified into different risk groups according to clinical history, hemodynamic status, cardiac biomarkers and imaging assessment of right ventricular (RV) function.

Traditionally, reperfusion therapy with systemic thrombolysis is the treatment of choice in high-risk PE, defined by sustained systemic arterial hypotension, cardiogenic shock, or the need for cardiopulmonary resuscitation.

In the setting of intermediate-risk PE,characterized by the absence of hemodynamic instability but elevated cardiac biomarkers or RV disfunction at imaging, the ESC guidelines recognize two sub-categories: intermediate-high if both signs are identified or intermediate-low, if only one of them is present.Approximately one quarter of hemodynamically stable patients with PE are at intermediate-risk, with mortality rates ranging from 3% to 15% if imaging or biomarker evidence of RV dilatation or dysfunction is present.4,5 In this subset of patients the optimal treatment strategy is still an object of debate.

A combination of ultrasound- based fragmentation of the thrombus and catheter-directed thrombolysis, requiring a reduced dose of the thrombolytic agent, has been developed. This localized therapy is currently recommended by the ESC guidelines (class IIa, LOE C) for patients with high-risk PE and contraindications for systemic thrombolysis or intermediate-high-risk PE and hemodynamic deterioration on anticoagulation treatment.

The investigators propose an observational cohort study aimed at assessing the impact on short and long-term outcome of ultrasound-assisted, catheter-directed thrombolysis using EKOSTM in a real-word population of subjects with acute intermediate-high risk PE treated in multiple Italian centers.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Alice Sacco, MD; Phone Number: 2565 0039026444; Email: alice.sacco@ospedaleniguarda.it
• Study Contact Backup: Name: Dario Brunelli, PhD; Phone Number: 6516 0039026444; Email: dario.brunelli@ospedaleniguarda.it

Study Locations

• Italy
  • Italia
    • Milan, Italia, Italy, 20162
      • Recruiting
      • ASST GOM Niguarda
      • Contact: Alice Sacco, MD; Phone Number: 2565 0039026444; Email: alice.sacco@ospedaleniguarda.it
      • Contact: Dario Brunelli, PhD; Phone Number: 6516 0039026444; Email: dario.brunelli@ospedaleniguarda.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

patients hospitalized with intermediate high-risk pulmonary embolism

Description

Inclusion Criteria

• Patients admitted with acute intermediate-high risk PE, defined according to ESC guidelines
• Symptoms onset within previous 14 days associated or not with deep venous thrombosis
• Confirmation of the PE by contrast-enhanced computed tomography of the chest with embolus located in at least one main or proximal lower lobe pulmonary artery
• Echocardiographic parameters of RV disfunction
• Patients with high-risk PE or hemodynamic deterioration on anticoagulation, who have absolute contraindications (high bleeding risk) to systemic thrombolysis and symptoms onset during the last 14 days. Patients with surgery-related embolic complications are also included (within 48 hours).

Exclusion Criteria

• Age < 18 years old
• Patients unable to give informed consent
• Pregnancy
• Patients received fibrinolytic drugs in the preceding 4 days
• Bleeding diathesis
• Known bleeding disorder
• Low platelet count (< 100.000/uL
• Gastrointestinal bleeding in the preceding 3 month
• Any ongoing known presence of malignant neoplasia months
• Advanced chronic kidney disease (defined as 11.000/uL)
• Gastrointestinal bleeding in the preceding 3 month
• Any ongoing known presence of malignant neoplasia at admission with survival rate < 6
• Advanced chronic kidney disease (defined as eGFR < 30 ml/min or on dialysis)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
EkoSonicTM Endovascular System (EKOSTM, Boston Scientific); Patients hospitalized with acute intermediate-high risk PE treated with ultrasound-assisted, catheter-directed thrombolysis using EKOSTM.	Procedure: ultrasound-assisted, catheter-directed thrombolysis; After 10 hours of alteplase infusion and EKOSTM ultrasound, the therapy is stopped, the EKOSTM catheter is removed, and the puncture site (internal jugular vein or femoral vein) has to be compressed.; Other Names: EkoSonicTM Endovascular System (EKOSTM, Boston Scientific)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
development of pulmonary hypertension	number of cases	6 months from treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of echocardiographic parameters	tricuspid annular plane excursion (TAPSE) (mm); right ventricle/left ventricle ratio (RV/LV) ratio (decimal); acceleration time (ACT) time (seconds); fractional area change (FAC); S' TDI RV (cm/sec); pulmonary artery systolic pressure (PAPs) (mmHg); tricuspid regurgitant velocity (TRV) (m/s)	24 hours after the treatment and at 3-6 months follow-up
death	death during hospital stay (number of events)	within 6 months from treatment
death	death from any cause (cancer, sepsis, respiratory failure, other) number of events	within 6 months from treatment
PE	PE recurrence (number of events)	within 6 months from treatment
Major bleeding within 6 months from treatment (Bleeding Academic Research Consortium-major bleedings defined as BARC 3-5 events; clinically relevant non major bleedings defined as BARC 2 event) (number of events)	Bleeding Academic Research Consortium-major bleedings defined as BARC 3-5 events; clinically relevant non major bleedings defined as BARC 2 event (number of events)	within 6 months from treatment
stroke	number of events	within 6 months from treatment
Re-hospitalization	Re-hospitalization (number of events)	within 6 months from treatment

Collaborators and Investigators

• Sponsor: Niguarda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pulmonary embolism; intermediate high-risk; Ultrasound-assisted; Catheter-directed Thrombolysis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 652-28112022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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