ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism

NCT ID: NCT01166997

Last Updated: 2021-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

EkoSonic Endovascular System

Intervention Type: DEVICE

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

Intravenous unfractionated heparin

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

Group Type: ACTIVE_COMPARATOR

Unfractionated heparin

Intervention Type: DRUG

Intravenous unfractionated heparin used for anticoagulation treatment

Interventions

EkoSonic Endovascular System

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

Intervention Type: DEVICE

Unfractionated heparin

Intravenous unfractionated heparin used for anticoagulation treatment

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EKOS Corporation

INDUSTRY

Sponsor Role: collaborator

Boston Scientific Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nils Kucher, Prof Dr med

Role: PRINCIPAL_INVESTIGATOR

Inselspital Bern, Kliniken für Angiologie und Kardiologie

Locations

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

Quakenbrück, , Germany

Helios Klinikum Siegburg

Siegburg, , Germany

SRH Zentralklinikum Suhl

Suhl, , Germany

Inselspital Bern, Kliniken fur Kardiologie and Angiologie

Bern, , Switzerland

Countries

Germany; Switzerland

References

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.

Reference Type: DERIVED

PMID: 24226805 (View on PubMed)

Other Identifiers

EKOS Protocol Number 08

Identifier Type: -

Identifier Source: org_study_id