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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Withdrawn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

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

NCT ID

NCT02378623

First Posted

February 27, 2015

Last Updated

November 15, 2018

Sponsor

Mayo Clinic

Collaborators

Bristol-Myers Squibb

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

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

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

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

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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