XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis
Condition: Pulmonary Embolism; Venous Thrombosis
MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Venous Thrombosis
Intervention: rivaroxaban; warfarin
Intervention description: Immediately following completion of alteplase infusion, patients will receive rivaroxaban 15 mg oral bid for 21 days followed by 20 mg oral daily.; Immediately following completion of alteplase infusion, patients will continue on unfractionated heparin or low-molecular weight heparin with initiation of warfarin adjusted to INR of 2-3.
Intervention MeSH terms: Warfarin; Rivaroxaban
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rivaroxaban; CDT (Catheter directed thrombolysis); PE (pulmonary embolism); NETs; factor Xa

Summary:

      The trial is an open-label, randomized, trial examining novel biomarkers of thrombosis in
      patients managed with rivaroxaban vs. standard care following treatment of pulmonary embolism
      (PE) with catheter-guided alteplase. Patients >18 years old who present with PE and are
      managed with catheter-guided alteplase will be screened for study inclusion. Patient's
      meeting inclusion/exclusion criteria will undergo informed consent. Immediately following
      completion of alteplase infusion, patients will be randomized to receipt of rivaroxaban 15 mg
      oral bid for 21 days followed by 20mg oral daily or continuation on unfractioned heparin or
      low-molecular weight heparin with initiation of warfarin adjusted to INR of 2-3. Blood
      samples will be taken within 2 hours of CDT completion prior to receipt of study treatment
      (study day 1), at 8h-12h, 24h, 48h, 5d (or prior to hospital discharge), and at 30 day
      follow-up. Clinical endpoints, including bleeding, evidence of thrombosis progression, and
      death will be tracked during index hospitalization and at follow-up 30 days post-discharge.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provisions of informed consent prior to any study specific procedure

          -  Diagnosis of acute PE

          -  Evidence of RV strain as defined by one of the following:

          -  1. an RV-to-LV diameter ratio>0.9

          -  2. elevated troponin

          -  3. elevated BNP

          -  Plan for CDT for PE.

        Exclusion Criteria:

          -  Arterial hypotension and cardiogenic shock at the time of enrollment. Arterial
             hypotension defined as a systolic arterial pressure <90mm Hg or a drop in systolic
             arterial pressure of at least 40 mm Hg for at least 15 minutes with tissue
             hypoperfusion and/or hypoxia)

          -  Hypersensitivity or other reaction to rivaroxaban

          -  Other indication for VKA than PE

          -  Creatinine clearance <30 ml/min

          -  Significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis)
             or ALT > 3 x ULN

          -  Life expectancy <3 months