Clinical trial NCT01166997: ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism
Official title: Randomized, Controlled Study Comparing EKOS EkoSonic Ultrasound Accelerated Thrombolysis to Anticoagulation in the Treatment of Sub-massive Pulmonary Embolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Submassive Pulmonary Embolism
Keywords: Pulmonary embolism
Pulmonary thromboembolism
anticoagulation
thrombolysis
ultrasound accelerated thrombolysis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: EKOS Corporation
First posted: 2010-07-21
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Reduction of RV/LV Ratio
timeFrame: 24 hours
measure: Major Bleeding and Intracranial Bleeding at 30 Days.
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Detmold
country: Germany
facility: Klinikum Lippe-Detmold
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
city: Greifswald
country: Germany
facility: Universitätsklinikum der Ernst-Moritz-Arndt-Universität,
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: München
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universität (LMU)
city: Quakenbrueck
country: Germany
facility: Christliches Krankenhaus Quakenbrueck
city: Siegburg
country: Germany
facility: Helios Klinikum Siegburg
city: Suhl
country: Germany
facility: SRH Zentralklinikum Suhl
city: Bern
country: Switzerland
facility: Inselspital Bern, Kliniken fur Kardiologie and Angiologie
Study officials:
affiliation: Inselspital Bern, Kliniken für Angiologie und Kardiologie
name: Nils Kucher, Prof Dr med
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.