ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism
Condition: Submassive Pulmonary Embolism
MeSH terms: Pulmonary Embolism; Embolism
Intervention: EkoSonic Endovascular System; Unfractionated heparin
Intervention description: The EkoSonic Endovascular System will be used to deliver < 20 mg of rt-PA ( Actilyse) directly into the occlusive pulmonary thrombus.; Intravenous unfractionated heparin used for anticoagulation treatment
Intervention MeSH terms: Heparin; Calcium heparin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Pulmonary embolism; Pulmonary thromboembolism; anticoagulation; thrombolysis; ultrasound accelerated thrombolysis

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