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

NCT02378623 | Withdrawn Phase 2 DMC

• 1 other identifier: 13-008633
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Patent Foramen Ovale; Cardiac Implantable Electronic Device

Keywords

paradoxical embolism; lead thrombus; ICD; Pacemaker; Cognitive decline; Stroke; TIA

Outcome Measures

Primary Outcomes (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).

  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

  2 years

Study Arms (2)

Apixaban

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Apixaban DRUG

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.

Also known as: Eliquis

Apixaban

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Foramen Ovale, Patent; Embolism, Paradoxical; Cognitive Dysfunction; Stroke

Interventions

apixaban

Condition Hierarchy (Ancestors)

Heart Septal Defects, Atrial; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Samuel Asirvatham, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Christopher DeSimone, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Paul Friedman, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 4, 2015
• Study Start: May 1, 2015
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: November 16, 2018

Record last verified: 2018-11

Locations

US (1)