Patent Foramen OvalePhase 2PARADOXNCT02378623
Patients With Patent Foramen Ovale and Endocardial Device Leads on Apixaban for Prevention of Paradoxical Emboli
A Phase 2 study testing Apixaban in people with Patent Foramen Ovale and Cardiac Implantable Electronic Device, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Patent Foramen Ovale, Cardiac Implantable Electronic Device
- What is being tested?
- Apixaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Jan 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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
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.
Read the 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.
- Being tested
- Apixaban, Placebo
- Keywords
- paradoxical embolism, lead thrombus, ICD, Pacemaker, Cognitive decline, Stroke, TIA
- Medical subject headings
- Foramen Ovale, Patent, Embolism, Paradoxical, Cognitive Dysfunction, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study startMay 2015
- Primary completionJan 2020 (estimated)
- Study completionJan 2020 (estimated)
Why it stopped: Sponsor withdrew funding - May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patent Foramen OvaleStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Christopher V. DeSimone, M.D., Ph.D., Mayo Clinic
- Investigators
- Samuel Asirvatham, MD, Principal investigator, Mayo ClinicChristopher DeSimone, MD, Principal investigator, Mayo ClinicPaul Friedman, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02378623
- Sponsor's protocol ID
- 13-008633
- Acronym
- PARADOX
- Status last verified
- Nov 2018
- First submitted
- 27 Feb 2015
- Last updated
- 16 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02378623
- Acronym / sponsor ID
- PARADOX / 13-008633
- Keywords
- paradoxical embolism, lead thrombus, ICD, Pacemaker, Cognitive decline, Stroke, TIA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor withdrew funding - May 2016
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- May 2015
- Primary completion
- Jan 2020 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Active comparator | Drug: ApixabanIntervention 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 |
| Placebo | Placebo comparator | Drug: PlaceboControl group: Matched placebo by mouth two times daily in addition to usual medical therapy. Planned treatment duration is 2 years. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApixabanAlso: EliquisPatients 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. | Drug | Apixaban |
| PlaceboPatients 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. | Drug | Placebo |
Primary outcome
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Asirvatham, MD principal investigator
Mayo Clinic
Christopher DeSimone, MD principal investigator
Mayo Clinic
Paul Friedman, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apixaban in people with Patent Foramen Ovale and Cardiac Implantable Electronic Device, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2018.