ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism (ULTIMA)

• ClinicalTrials.gov Identifier: NCT01166997
• Recruitment Status: Completed
• First Posted: July 21, 2010
• Results First Posted: October 18, 2016
• Last Update Posted: October 18, 2016
• Sponsor: EKOS Corporation
• Information provided by (Responsible Party): EKOS Corporation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Submassive Pulmonary Embolism	Device: EkoSonic Endovascular System; Drug: Unfractionated heparin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled Study Comparing EKOS EkoSonic Ultrasound Accelerated Thrombolysis to Anticoagulation in the Treatment of Sub-massive Pulmonary Embolism
• Study Start Date: July 2010
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ultrasound accelerated thrombolysis; 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.	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.
Active Comparator: Intravenous unfractionated heparin; Patients in this arm will receive the standard of care: intravenous unfractionated heparin used as anti-coagulation treatment.	Drug: Unfractionated heparin; Intravenous unfractionated heparin used for anticoagulation treatment

Outcome Measures

Primary Outcome Measures :

1. Reduction of RV/LV Ratio [ Time Frame: 24 hours ]
   Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.
2. Major Bleeding and Intracranial Bleeding at 30 Days. [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

Klinikum Lippe-Detmold

Detmold, Germany, 32756

Klinikum Dortmund gGmbH

Dortmund, Germany, 44137

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Germany, 01307

Universitätsklinikum der Ernst-Moritz-Arndt-Universität,

Greifswald, Germany, 17475

Universitätsklinikum Heidelberg

Heidelberg, Germany, 69120

Klinikum der Ludwig-Maximilians-Universität (LMU)

München, Germany, 81377

Christliches Krankenhaus Quakenbrueck

Quakenbrueck, Germany, 49610

Helios Klinikum Siegburg

Siegburg, Germany, 53721

SRH Zentralklinikum Suhl

Suhl, Germany, 98527

Switzerland

Inselspital Bern, Kliniken fur Kardiologie and Angiologie

Bern, Switzerland, 3010

Sponsors and Collaborators

EKOS Corporation

Investigators

• Principal Investigator: Nils Kucher, Prof Dr med; Inselspital Bern, Kliniken für Angiologie und Kardiologie

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kucher N, Boekstegers P, Müller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Müller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Härtel D, Grünwald 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.

• Responsible Party: EKOS Corporation
• ClinicalTrials.gov Identifier: NCT01166997
• Other Study ID Numbers: EKOS Protocol Number 08
• First Posted: July 21, 2010
• Results First Posted: October 18, 2016
• Last Update Posted: October 18, 2016
• Last Verified: August 2016

Keywords provided by EKOS Corporation:

Pulmonary embolism; Pulmonary thromboembolism; anticoagulation; thrombolysis; ultrasound accelerated thrombolysis

Additional relevant MeSH terms:

Pulmonary Embolism; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Heparin; Calcium heparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action