Peripheral Systemic Thrombolysis Versus Catheter Directed Thrombolysis for Submassive PE
Condition: Pulmonary Embolism; Pulmonary Hypertension; Thromboembolism; Right Ventricular Dysfunction
MeSH terms: Hypertension, Pulmonary; Pulmonary Embolism; Embolism; Thromboembolism; Ventricular Dysfunction; Ventricular Dysfunction, Right
Study type: Interventional
Phase: Phase 4

Summary: 
      To determine whether peripheral low dose systemic thrombolysis (PLST) is non-inferior to
      catheter directed acoustic pulse thrombolysis (ACDT) in improving RV function and reducing
      pulmonary artery pressures in submassive pulmonary embolism (PE)
    

Detailed description: 
      Acute pulmonary embolism (PE) is a life-threatening event associated with high morbidity and
      mortality. With more than 100,000 deaths per year, PE constitutes the third most common
      cardiovascular cause of death following myocardial infarction and stroke. In non massive PE,
      anticoagulation is the treatment of choice. Advanced treatment options such as systemic
      thrombolysis in submassive and massive PE help reduce mortality but unfortunately are
      associated with bleeding complications such as a 2 to 5% risk of hemorrhagic stroke.This has
      led to development of pharmaco-mechanical therapies such as catheter directed thrombolysis
      (CDT).

      Current guidelines advocate against the use of full dose systemic thrombolysis for acute
      submassive PE in all patients unless the bleeding risk is very low. CDT has shown efficiency
      in reducing right ventricular strain and pulmonary hypertension without increasing bleeding
      complications in trial populations. Ultrasound assisted CDT (ACDT) is an established
      treatment modality for acute PE which utilizes high frequency low power ultrasonic waves. It
      is FDA approved for sub-massive and massive pulmonary embolism. However, ultrasound does not
      breakdown the thrombus itself but increases the permeability for thrombolytic drugs. The
      ULTIMA trial showed ACDT was superior to anticoagulation treatment in reducing pulmonary
      hypertension (PH) and right ventricular dilatation in submassive and massive PE. The trial
      also reported no intracranial hemorrhage. The exact benefit and mechanism of ACDT in
      dissolving clots is still not clear. Recently, the PERFECT registry described 100 patients
      who underwent CDT (64%) and ACDT (46%) for PE, the study showed no difference in reduction of
      pulmonary artery pressures.

      ACDT requires the placement of catheters in the pulmonary arteries in a catheterization
      laboratory by an interventional cardiologist/radiologist through the internal jugular
      vein/femoral vein and catheters are kept for 12-24 hrs to infuse recombinant tissue
      plasminogen activator (r-tpa). While many healthcare systems have developed a pulmonary
      embolism response team (PERT) to make a prompt therapeutic decision in submassive and massive
      pulmonary embolism management. However, it is not uncommon for CDT to be delayed (sometimes >
      12 hours) after the initial diagnosis due to the availability of the interventional
      cardiologist. Furthermore, placement of pulmonary catheters in CDT can have the risk, albeit
      low, of pulmonary vasculature injury.

      The investigators hypothesize that low dose thrombolytic therapy can be administered through
      a peripheral vein. PLST is rapidly administrable and does not require placement in a
      catheterization laboratory by an interventional cardiologist. In addition, the use of low
      dose r-tpa reduces risk of major bleeding complications. The investigators aim to see if
      equivalent low dose r-tpa given peripherally i.e PLST is non-inferior to ACDT for the
      treatment of submassive PE. Both treatments will be compared in safety, efficacy and overall
      cardiopulmonary function.
    

Intervention name(s): Alteplase; EKOS
Intervention type(s): Drug; Device
Intervention description(s): As stated before, low dose r-tpa will be administered through a peripheral vein for PLST.; As stated before, the EKos device will be used for ultrasound assisted catheter directed thrombolysis or ACDT, same dose t-tpa will administered through the pulmonary catheter. It will be given at a fixed dose over 24 hours.
Other intervention name(s): Peripheral low dose systemic thrombolysis (PLST); Ultrasound assisted catheter directed thrombolysis (ACDT)
Intervention MeSH terms: Tissue Plasminogen Activator
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study will be a prospective randomized interventional study. Patients referred to Southside hospital will be consented to take part in the study. After obtaining written informed consent, investigators will subsequently enroll 158 consecutive patients (aged> 18 years) randomized in a serial 1:1 allocation for either low dose PLST or ACDT for submassive pulmonary embolism.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Alteplase; submassive pulmonary embolism; Thrombolysis; pulmonary catheter