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Patients With Patent Foramen Ovale and Endocardial Device Leads on Apixaban for Prevention of Paradoxical Emboli (PARADOX)

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ClinicalTrials.gov Identifier: NCT02378623
Recruitment Status : Withdrawn (Sponsor withdrew funding - May 2016)
First Posted : March 4, 2015
Last Update Posted : November 16, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Christopher V. DeSimone, M.D., Ph.D., Mayo Clinic

Brief Summary:
Patients with a patent foramen ovale in the setting of endocardially placed cardiac implantable electronic devices such as pacemakers, defibrillators, or resynchronization therapies are likely at higher risk for paradoxical embolic events from device lead thrombus. The investigators are conducting this study to determine if the anticoagulant medication Apixaban is more effective at reducing MRI detected brain lesions compared to placebo.

Condition or disease Intervention/treatment Phase
Patent Foramen Ovale Cardiac Implantable Electronic Device Drug: Apixaban Drug: Placebo Phase 2

Detailed Description:

This is a prospective, double-blinded, placebo-controlled, randomized controlled trial (RCT).

400 patients who meet the study eligibility criteria and consent for enrollment will be randomized in a 1:1 ratio to intervention with apixaban or control group with placebo. The randomization will be performed by a computer generated block randomization protocol. The majority of patients will begin intervention with Apixaban or placebo at the time of cardiac device placement (n approximately 300), and at least a quarter of the randomized patients (n ≥100) will include preexisting CIED (≥6 months) in place. Each patient will undergo a baseline MRI and a comprehensive cognitive screening examination. Repeat MRI and cognitive assessment will be performed at a follow-up period of two years from date of randomization (or less if clinical stroke/TIA occurs prior to this follow-up period). All subjects will receive a phone call at 6 months, 12 months, and 18 months post-randomization to assess for endpoints and adverse events, as well as changes in clinical status, medications, and to assess study medication compliance.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PARADOX Trial: A Prospective, Double-Blind, Randomized Controlled Trial in Patients With Patent Foramen Ovale and Endocardial Device Leads on Apixaban for Prevention of Paradoxical Emboli
Study Start Date : May 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Apixaban

Arm Intervention/treatment
Active Comparator: Apixaban
Intervention group: Apixaban 5 mg by mouth two times daily in addition to usual medical therapy (or 2.5 mg two times daily for subjects who fulfilled any 2 of the following criteria: age≥80 years, body weight≤60kg, and/or serum creatinine≥1.5 mg/dL). Planned treatment duration is 2 years
Drug: Apixaban
Patients who meet the study eligibility criteria and consent for enrollment will be randomized in a 1:1 ratio to intervention with apixaban or control group with placebo. The randomization will be performed by a computer generated block randomization protocol. Randomization will be stratified according to pre-existing CIED (≥6 months) vs. new implantation (<6 months from date of implant), in order to ensure at least 25% of patients have longstanding lead placement.
Other Name: Eliquis

Placebo Comparator: Placebo
Control group: Matched placebo by mouth two times daily in addition to usual medical therapy. Planned treatment duration is 2 years.
Drug: Placebo
Patients who meet the study eligibility criteria and consent for enrollment will be randomized in a 1:1 ratio to intervention with apixaban or control group with placebo. The randomization will be performed by a computer generated block randomization protocol. Randomization will be stratified according to pre-existing CIED (≥6 months) vs. new implantation (<6 months from date of implant), in order to ensure at least 25% of patients have longstanding lead placement.




Primary Outcome Measures :
  1. Increase in number of new brain lesions detected on MRI ≥3 mm in size at 2 years post-baseline MRI (or earlier if premature termination of study follow-up). [ Time Frame: 2 years ]
    The primary objective of this study is to determine whether medical therapy with apixaban lowers the rate of new MRI cerebral lesions compared to placebo in pacemaker, defibrillator, and resynchronization device therapy recipients with a PFO



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  • A clinical indication for a trans venous pacemaker, ICD, or CRT device, or presence of a pre-existing endovascular CIED
  • Presence of a PFO (regardless of shunt direction) confirmed with trans-esophageal or trans-thoracic echocardiography with color flow Doppler and/or agitated saline
  • Absence of any contraindication for anticoagulation
  • Absence of a clinical indication for systemic anticoagulation
  • Ability to give informed consent for the trial
  • Able to undergo head MRI and consent for MRI study to be performed in presence of CIED

Exclusion:

  • Patients with a survival expectancy of less than one year
  • Patients who require systemic anticoagulation for any established clinical indication (excluding the presence of PFO with CIED)
  • Patients with an atrial or ventricular septal defect that is hemodynamically significant and requires repair as suggested by the ACC/AHA 2008 guidelines on evaluation and treatment of adult congenital heart diseases
  • Absence of a CIED or no clinical indication for a trans venous CIED
  • Contraindication to undergoing an MRI
  • Patients with an active infection that cannot be treated successfully prior to randomization
  • Women who are pregnant or breastfeeding, or women of child-bearing potential who do not wish to use an effective method of birth control during the course of study in a manner such that the risk of failure is minimized
  • Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
  • Known sensitivity to any of the active substances or their excipients to be administered during dosing with study medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02378623


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Bristol-Myers Squibb
Investigators
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Principal Investigator: Samuel Asirvatham, MD Mayo Clinic
Principal Investigator: Christopher DeSimone, MD Mayo Clinic
Principal Investigator: Paul Friedman, MD Mayo Clinic

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Responsible Party: Christopher V. DeSimone, M.D., Ph.D., PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02378623     History of Changes
Other Study ID Numbers: 13-008633
First Posted: March 4, 2015    Key Record Dates
Last Update Posted: November 16, 2018
Last Verified: November 2018
Keywords provided by Christopher V. DeSimone, M.D., Ph.D., Mayo Clinic:
paradoxical embolism
lead thrombus
ICD
Pacemaker
Cognitive decline
Stroke
TIA
Additional relevant MeSH terms:
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Foramen Ovale, Patent
Embolism, Paradoxical
Heart Septal Defects, Atrial
Heart Septal Defects
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Embolism and Thrombosis
Vascular Diseases
Thromboembolism
Apixaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants