ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism

NCT01166997 | Completed Phase 3 Results DMC

• 1 other identifier: EKOS Protocol Number 08
• Study Type: interventional
• Target: 59
• Locations: 2 countries
• Sites: 10

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.

Conditions

Submassive Pulmonary Embolism

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Reduction of RV/LV Ratio

  Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.

  24 hours

• 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

Study Arms (2)

Ultrasound accelerated thrombolysis

EXPERIMENTAL

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

Intravenous unfractionated heparin

ACTIVE COMPARATOR

Patients in this arm will receive the standard of care: intravenous unfractionated heparin used as anti-coagulation treatment.

Drug: Unfractionated heparin

Interventions

EkoSonic Endovascular System DEVICE

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

Ultrasound accelerated thrombolysis

Unfractionated heparin DRUG

Intravenous unfractionated heparin used for anticoagulation treatment

Intravenous unfractionated heparin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• EKOS Corporation: collaborator

Study Sites (10)

Klinikum Lippe-Detmold

Detmold, 32756, Germany

Location

Klinikum Dortmund gGmbH

Dortmund, 44137, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum der Ernst-Moritz-Arndt-Universität,

Greifswald, 17475, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Klinikum der Ludwig-Maximilians-Universität (LMU)

München, 81377, Germany

Location

Christliches Krankenhaus Quakenbrueck

Quakenbrück, 49610, Germany

Location

Helios Klinikum Siegburg

Siegburg, 53721, Germany

Location

SRH Zentralklinikum Suhl

Suhl, 98527, Germany

Location

Inselspital Bern, Kliniken fur Kardiologie and Angiologie

Bern, 3010, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 24226805 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism

Interventions

Heparin

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Lynn Allen
• Organization: EKOS Corporation

Lynn.Allen@ekoscorp.com

4254153100

Study Officials

• Nils Kucher, Prof Dr med

  Inselspital Bern, Kliniken für Angiologie und Kardiologie

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 21, 2010
• Study Start: July 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 19, 2021
• Results First Posted: October 18, 2016

Record last verified: 2021-07

Locations

DE (9); CH (1)