ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism

Phase 3

Completed

• Conditions: Submassive Pulmonary Embolism
• Interventions: Drug: Unfractionated heparin; Device: EkoSonic Endovascular System

• Registration Number: NCT01166997
• Lead Sponsor: Boston Scientific Corporation

Brief Summary

The ULTIMA study is intended to prove that in patients with pulmonary embolism and a right ventricular end diastolic diameter to left ventricular end diastolic diameter ratio ≥1 (RV/LV ratio) will benefit from treatment with ultrasound accelerated thrombolysis (rt-PA) as compared to unfractionated heparin anticoagulation. Specifically, at 24 hours the RV/LV ratio will be significantly reduced in the treatment arm compared to the control arm.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-15
• Study First Submitted QC: 2010-07-20
• Study First Posted: 2010-07-21
• Primary Completion: 2013-04
• Study Completion: 2013-05
• Results First Submitted: 2016-08-23
• Results First Submitted QC: 2016-08-24
• Results First Posted: 2016-10-18
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-15
• Last Update Posted: 2021-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

• Patients with acute PE symptoms < 14 days.
• Filling defect by contrast-enhanced chest CT in at least one main or proximal lower lobe pulmonary artery
• Right ventricular dysfunction confirmed by echocardiography where the RV/LV end diastolic diameter ratio is ≥ 1.0.

Exclusion Criteria

• Age less than 18 years or greater than 80 years
• Index PE symptom duration > 14 days
• Insufficient echocardiographic image quality in the apical or subcostal four-chamber view that prohibits the measurement of the right and left ventricular end-diastolic dimensions
• Known significant bleeding risk
• Administration of thrombolytic agents, e.g., tissue plasminogen activator, streptokinase, or urokinase, within the previous 4 days
• Active bleeding
• Known bleeding diathesis
• Known coagulation disorder, platelet count < 100 000/mm3, or previous use of vitamin K antagonists with INR > 2.5
• History of any intracranial or intraspinal surgery or trauma or intracranial/intraspinal bleed
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Recent (< 3 months) GI bleeding.
• Recent (< 3 months) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure.
• Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
• Estimated glomerular filtration rate (eGFR) < 50 ml/min as calculated by the Cockroft formula.
• Hemodynamic collapse at presentation defined as: need for cardiopulmonary resuscitation; or systolic blood pressure < 90 mm Hg for at least 15 min, or drop of systolic blood pressure by at least 40 mm Hg for at least 15 min with signs of end organ hypoperfusion (cold extremities or low urinary output < 30 mL/h or mental confusion); or need for catecholamine administration to maintain adequate organ perfusion and a systolic blood pressure of > 90 mm Hg.
• Severe hypertension on repeated readings (systolic > 180 mmHg or diastolic > 105 mmHg).
• Pregnant, lactation or parturition within the previous 30 days (positive pregnancy test, women of childbearing age must be tested).
• Participating in any other investigational drug or device study.
• Life expectancy < 90 days.
• Inability to comply with study assessments (e.g. due to geographic distance).
• Previous enrollment in this study
• Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.
• Known right-to-left shunt, for example from large patent foramen ovale or atrial septal defect
• Large (>10 mm) right atrial or right ventricular thrombus

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous unfractionated heparin	Unfractionated heparin	Patients in this arm will receive the standard of care: intravenous unfractionated heparin used as anti-coagulation treatment.
Ultrasound accelerated thrombolysis	EkoSonic Endovascular System	Patients in this arm will receive anti-coagulation (intravenous unfractionated heparin) plus the EkoSonic Endovascular System will be used to deliver a low dose \<20mg rt-PA (Actilyse) directly into the occlusive pulmonary thrombus.

Primary Outcome Measures

Name	Time	Method
Reduction of RV/LV Ratio	24 hours	Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.
Major Bleeding and Intracranial Bleeding at 30 Days.	30 days	Bleeding will be classified as major if it is associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g., intracranial, intraspinal). To aid in evaluating the relationship of bleeding events to rt-PA administration, they will also be categorized by whether they occurred within 3 days after the initiation of thrombolytic therapy.

Trial Locations

Locations (10)

Inselspital Bern, Kliniken fur Kardiologie and Angiologie; 🇨🇭 Bern, Switzerland

Klinikum Dortmund gGmbH; 🇩🇪 Dortmund, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Christliches Krankenhaus Quakenbrueck; 🇩🇪 Quakenbrueck, Germany

Universitätsklinikum der Ernst-Moritz-Arndt-Universität,; 🇩🇪 Greifswald, Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden; 🇩🇪 Dresden, Germany

Klinikum Lippe-Detmold; 🇩🇪 Detmold, Germany

Helios Klinikum Siegburg; 🇩🇪 Siegburg, Germany

Klinikum der Ludwig-Maximilians-Universität (LMU); 🇩🇪 München, Germany

SRH Zentralklinikum Suhl; 🇩🇪 Suhl, Germany