Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Pulmonary Embolism
Condition: Pulmonary Embolism and Thrombosis
MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Embolism and Thrombosis
Intervention: Ekosonic® Endovascular Device ultrasonic infusion catheter; Recombinant tissue plasminogen activator
Intervention description: r-tPA will be administered via EKOS.; Recombinant tissue plasminogen activator will be administered as per the dose and schedule specified in the arm.
Intervention MeSH terms: Plasminogen; Tissue Plasminogen Activator
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The objective is to determine the optimum dose of thrombolytic and duration of the ultrasound
      procedure (together defined as the APT Procedure) as a treatment for acute submassive
      pulmonary embolism (PE). Symptomatic submassive PE are participants with acute (less than or
      equal to [≤]14 days) PE with normal systemic arterial blood pressure (greater than [>] 90
      mmHg) and evidence of RV dysfunction (right ventricular to left ventricular diameter ratio,
      that is; RV/LV ratio greater than or equal to [≥] 0.9). Participants with submassive PE will
      be randomized to one of four APT treatment groups: ultrasound of 2 and 6 hours (hrs) with
      r-tPA 2 milligrams (mg)/hr/catheter and ultrasound 4 and 6 hours with r-tPA, 1
      mg/hr/catheter. On 08 June 2016, randomization into treatment group 4 (APT/6 hours-r-tPA/2
      mg/hr/catheter) was closed following a reported intracranial hemorrhage (ICH) and death in a
      study participant in this arm.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female greater than or equal to (≥) 18 years of age and less than or equal to
             (≤) 75 years of age.

          2. CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary
             artery).

          3. PE symptom duration ≤14 days.

          4. Submassive PE: RV/LV diameter ≥ 0.9 from CTA and hemodynamically stable. For
             Participants in UK Sites: Submassive PE: RV/LV diameter ≥ 0.9 from CTA,
             hemodynamically stable and an elevated biomarker.

          5. Must be treated within 48 hours of diagnosis of PE by CTA.

          6. Signed Informed consent obtained from subject or Legally Authorized Representative.

        Exclusion Criteria:

          1. Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial
             or intraspinal disease within one year.

          2. Recent (within one month) or active bleeding from a major organ.

          3. Major surgery within seven days of screening for study enrollment.

          4. Clinician deems the subject high-risk for catastrophic bleeding.

          5. History of heparin-induced thrombocytopenia (HIT).

          6. Catheter-based pharmacomechanical treatment for PE within 3 days of study enrollment.

          7. Systolic blood pressure (SBP) less than 90 mm Hg and/or use of vasopressors.

          8. Cardiac arrest (including pulseless electrical activity and asystole) requiring active
             cardiopulmonary resuscitation (CPR).

          9. Evidence of irreversible neurological compromise.

         10. Life expectancy < one year. For Participants in UK Sites: Life expectancy < one year
             or enrollment in hospice care.

         11. Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to
             inclusion in the study.

         12. Out-of-Range Laboratory Values: Hematocrit < 30%, Platelets < 100 thousand/microliter
             (μL), International normalized ratio (INR) > 3.

         13. Creatinine outside the normal range for the treating institution.

         14. Participant is pregnant (positive pregnancy test; women of childbearing capacity must
             be tested) or breast feeding.

         15. Active cancer (metastatic, progressive, or treated within the last 6 months).
             Exception: participants with non-melanoma primary skin cancers are eligible to
             participate in the study.

         16. Known allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated
             contrast except for mild-moderate contrast allergies for which steroid pre-medication
             can be used.

         17. History of any hematologic disease potentially involving abnormal platelet number or
             function.