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: July 19, 2021
• Sponsor: Boston Scientific Corporation
• Collaborator: EKOS Corporation
• Information provided by (Responsible Party): Boston Scientific Corporation

Tracking Information

• First Submitted Date: July 15, 2010
• First Posted Date: July 21, 2010
• Results First Submitted Date: August 23, 2016
• Results First Posted Date: October 18, 2016
• Last Update Posted Date: July 19, 2021
• Study Start Date: July 2010
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 24, 2016)

• Reduction of RV/LV Ratio [ Time Frame: 24 hours ]
  Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.
• 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.

Original Primary Outcome Measures (submitted: July 20, 2010)

Reduction of RV/LV ratio [ Time Frame: 24 hours ]

RV/LV ratio will be measured by echocardiography at baseline. RV/LV ratio will be measured again by echocardiography at 24 hours.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: 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

Study Arms

• 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.
  Intervention: Device: EkoSonic Endovascular System
• Active Comparator: Intravenous unfractionated heparin
  Patients in this arm will receive the standard of care: intravenous unfractionated heparin used as anti-coagulation treatment.
  Intervention: Drug: Unfractionated heparin

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 11, 2013): 59
• Original Estimated Enrollment (submitted: July 20, 2010): 50
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Switzerland

Administrative Information

• NCT Number: NCT01166997
• Other Study ID Numbers: EKOS Protocol Number 08
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boston Scientific Corporation
• Original Responsible Party: Principle Investigator: Nils Kucher, MD, Inselspital Bern Switzerland
• Current Study Sponsor: Boston Scientific Corporation
• Original Study Sponsor: EKOS Corporation
• Collaborators: EKOS Corporation

Investigators

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

• PRS Account: Boston Scientific Corporation
• Verification Date: July 2021