Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis (XENITH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02506985
Recruitment Status : Terminated
First Posted : July 23, 2015
Results First Posted : September 27, 2018
Last Update Posted : September 27, 2018
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Susan Smyth, University of Kentucky

Tracking Information
First Submitted Date  ICMJE June 17, 2015
First Posted Date  ICMJE July 23, 2015
Results First Submitted Date  ICMJE February 15, 2018
Results First Posted Date  ICMJE September 27, 2018
Last Update Posted Date September 27, 2018
Study Start Date  ICMJE July 2015
Actual Primary Completion Date June 29, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • Change in Markers of NETosis at 12h Compared to Baseline [ Time Frame: 12h ]
    Change in Markers of NETosis at 12h Compared to Baseline
  • Change in Markers of NETosis at 24h Compared to Baseline [ Time Frame: 24h ]
    Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 48h Compared to Baseline [ Time Frame: 48h ]
    Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 5 Days (or Day of Hospital Discharge) Compared to Baseline [ Time Frame: 5 days (or day of hospital discharge) ]
    Change in Markers of NETosis at 5 days (or day of hospital discharge) Compared to Baseline. Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 30 Days Compared to Baseline [ Time Frame: 30 days ]
    Values will be reported in comparison to baseline in the two treatment groups.
Original Primary Outcome Measures  ICMJE
 (submitted: July 21, 2015)
  • Change in Markers of NETosis at 12h Compared to Baseline [ Time Frame: 12h ]
    Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 24h Compared to Baseline [ Time Frame: 24h ]
    Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 48h Compared to Baseline [ Time Frame: 48h ]
    Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 5 Days (or Day of Hospital Discharge) Compared to Baseline [ Time Frame: 5 days (or day of hospital discharge) ]
    Values will be reported in comparison to baseline in the two treatment groups.
  • Change in Markers of NETosis at 30 Days Compared to Baseline [ Time Frame: 30 days ]
    Values will be reported in comparison to baseline in the two treatment groups.
Change History Complete list of historical versions of study NCT02506985 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis
Official Title  ICMJE XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis
Brief 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.
Detailed Description Catheter-guided alteplase has a growing role in the management of acute pulmonary embolism (PE). Following a 12-24 hour alteplase infusion (for bilateral or unilateral PE, respectively) patients are routinely managed with therapeutic unfractionated heparin (UFH) as a bridge to chronic warfarin therapy. It is our desire to study the effects of rivaroxaban vs. standard care following catheter-guided alteplase thrombolytic therapy (CDT) in patients with acute pulmonary embolism. Use of rivaroxaban may offer several important advantages compared to standard therapy in this setting. Among these is the potential for rivaroxaban to improve novel biomarkers of thrombosis including inhibition neutrophil extracellular traps (NETs), tissue factor-positive microparticles, and markers of inflammation. Neutrophil release of extracellular DNA may provide a scaffold upon which venous thrombosis propagates. NETs are associated with thrombus organization. Their dissolution may facilitate thrombolysis. Circulating DNA, a surrogate marker for NETs, is elevated 2-3 fold in patients with venous thromboembolism (VTE) and correlates strongly with plasma myeloperoxidase (MPO), an inflammatory marker of neutrophil and monocyte activation. The investigators have previously demonstrated that heparin can trigger MPO release from leukocytes. Thus, it is resonable to speculate that anti-Xa therapy may reduce inflammation, MPO, and NET levels in circulation. Further, the investigators have observed that catheter-directed thrombolysis may increase length of stay (time frame = 8 hours to 30 days following administration of study drugs) and the investigators would also propose treatment with rivaroxaban may balance this by eliminating a "bridging" period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pulmonary Embolism
  • Venous Thrombosis
Intervention  ICMJE
  • Drug: rivaroxaban
    Immediately following completion of alteplase infusion, patients will receive rivaroxaban 15 mg oral bid for 21 days followed by 20 mg oral daily.
    Other Name: Xarelto
  • Drug: warfarin
    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.
    Other Name: Coumadin
Study Arms  ICMJE
  • Experimental: rivaroxaban
    For the first 3 weeks, patients will receive rivaroxaban 15mg twice-daily; thereafter they will take rivaroxaban 20mg once-daily as per the drug label. Rivaroxaban will be initiated immediately following completion of alterplase infusion, and heparin will be discontinued at the time of rivaroxaban administration.
    Intervention: Drug: rivaroxaban
  • Experimental: heparin-warfarin
    Unfractioned heparin (UFH), following hospital protocol to achieve a target PTT or enoxaparin, 1.0mg/kg twice-daily, for a minimal duration of treatment of 5 days. Warfarin may be started on the night after CDT. UFH or enoxaparin should continue until the INR is >= 2.0 on two consecutive measurements at least 24 hours apart with an advised overlap with VKA for 4 to 5 days. VKA dosages will be adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0).
    Intervention: Drug: warfarin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 8, 2016)
10
Original Estimated Enrollment  ICMJE
 (submitted: July 21, 2015)
60
Actual Study Completion Date  ICMJE June 29, 2016
Actual Primary Completion Date June 29, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02506985
Other Study ID Numbers  ICMJE 15-0275-F6A
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Susan Smyth, University of Kentucky
Study Sponsor  ICMJE Susan Smyth
Collaborators  ICMJE Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: Susan S Smyth, MD PhD University of Kentucky
PRS Account University of Kentucky
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP