ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism

Submassive Pulmonary Embolism Clinical Trial

— ULTIMA  

Official title:

Randomized, Controlled Study Comparing EKOS EkoSonic Ultrasound Accelerated Thrombolysis to Anticoagulation in the Treatment of Sub-massive Pulmonary Embolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01166997
• Other study ID #: EKOS Protocol Number 08
• Status: Completed
• Phase: Phase 3
• Start date: July 2010
• Est. completion date: May 2013

Study information

• Verified date: July 2021
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: May 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism
• Submassive Pulmonary Embolism

Intervention

Device:
• EkoSonic Endovascular System
The EkoSonic Endovascular System will be used to deliver < 20 mg of rt-PA ( Actilyse) directly into the occlusive pulmonary thrombus.

Drug:
• Unfractionated heparin
Intravenous unfractionated heparin used for anticoagulation treatment

Locations

Country	Name	City	State
Germany	Klinikum Lippe-Detmold	Detmold
Germany	Klinikum Dortmund gGmbH	Dortmund
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Universitätsklinikum der Ernst-Moritz-Arndt-Universität,	Greifswald
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Klinikum der Ludwig-Maximilians-Universität (LMU)	München
Germany	Christliches Krankenhaus Quakenbrueck	Quakenbrueck
Germany	Helios Klinikum Siegburg	Siegburg
Germany	SRH Zentralklinikum Suhl	Suhl
Switzerland	Inselspital Bern, Kliniken fur Kardiologie and Angiologie	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Boston Scientific Corporation	EKOS Corporation

Countries where clinical trial is conducted

Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction of RV/LV Ratio	Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.	24 hours
Primary	Major Bleeding and Intracranial Bleeding at 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.	30 days