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

Primary Purpose

Patent Foramen Ovale, Cardiac Implantable Electronic Device

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Apixaban
Placebo
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Patent Foramen Ovale focused on measuring paradoxical embolism, lead thrombus, ICD, Pacemaker, Cognitive decline, Stroke, TIA

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Apixaban

Placebo

Arm Description

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

Control group: Matched placebo by mouth two times daily in addition to usual medical therapy. Planned treatment duration is 2 years.

Outcomes

Primary Outcome Measures

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).
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

Secondary Outcome Measures

Full Information

First Posted
February 27, 2015
Last Updated
November 15, 2018
Sponsor
Mayo Clinic
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02378623
Brief Title
Patients With Patent Foramen Ovale and Endocardial Device Leads on Apixaban for Prevention of Paradoxical Emboli
Acronym
PARADOX
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 Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor withdrew funding - May 2016
Study Start Date
May 2015 (undefined)
Primary Completion Date
January 2020 (Anticipated)
Study Completion Date
January 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Foramen Ovale, Cardiac Implantable Electronic Device
Keywords
paradoxical embolism, lead thrombus, ICD, Pacemaker, Cognitive decline, Stroke, TIA

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apixaban
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Control group: Matched placebo by mouth two times daily in addition to usual medical therapy. Planned treatment duration is 2 years.
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
Eliquis
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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 Measure Information:
Title
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).
Description
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
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel Asirvatham, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christopher DeSimone, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Friedman, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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