Inflammation, Fibrosis and Risk of Recurrence After Atrial Fibrillation Ablation (FIBRO-RISK)

July 30, 2022 updated by: Cardio Med Medical Center

Impact of Inflammation-mediated Myocardial Fibrosis on the Risk of Recurrence After Successful Ablation of Atrial Fibrillation - the FIBRO-RISK Study

FIBRO-RISK study aims to investigate the impact of inflammatory-mediated myocardial fibrosis on the risk of recurrence after successful ablation of atrial fibrillation. The level of systemic inflammation in the pre-ablation and immediate post-ablation period will be assessed on the basis of serum levels of inflammatory biomarkers (hs-CRP, matrix metalloproteases, interleukin-6), while the level of cardiac fibrosis will be determined based on MRI imaging associated with complex post-processing techniques for mapping myocardial fibrosis at the level of left atrium and left ventricle. At the same time, the amount of epicardial fat will serve as an indirect marker of localized inflammation and will be determined at different levels in the heart (surrounding left atrium, right atrium or the entire heart), while ventricular function will be assessed on the basis of serum levels of NT pro-BNP prior to the procedure. All these parameters will be investigated in patients with successful ablation of AF, who will be divided into 2 groups: group 1 - patients who develop AF recurrence at 1-year, and group 2 - patients with no recurrence of AF at 1-year. In all patients, the following biomarkers will be determined: serum levels of inflammatory biomarkers and NT-proBNP at 24 hours and 1 year post-procedure, the amount of myocardial fibrosis at the level of left atrium and left ventricle at baseline +/- 7 days and the amount of epicardial fat surrounding left atrium, right atrium and the entire heart at baseline +/- 7 days.

The primary endpoint of the study will be represented by the rate of AF recurrence at 1-year post ablation, documented by either ECG or Holter monitoring.

The secondary endpoints of the study will be:

  • rate of re-hospitalization
  • rate of survival without relapse
  • rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The prevalence of atrial fibrillation (AF) is on the rise, being the most frequent sustained supraventricular arrhythmia and a health issue by its increased morbidity and mortality. In most of the cases, myocardial tissue located at the level of the pulmonary veins represents the trigger for atrial fibrillation. The pathophysiology of AF is still incompletely understood, several studies suggesting that profibrotic and inflammatory processes have a crucial role in the development of AF. So far the success rate of AF ablation is not very high, reaching 70% in patients with paroxysmal AF and 50% in cases with persistent AF. Several risk factors for the occurrence and recurrence of AF have been described in the literature, including left atrial enlargement, left ventricular dysfunction, epicardial fat volume, and myocardial fibrosis caused by local atrial inflammation. What remains to be investigated is the relationship between these risk factors and the recurrence of AF after radiofrequency catheter ablation using advanced 3D mapping system.

This is a clinical prospective, descriptive, single-center study which will be carried out in the Center of Advanced Research in Multimodal Cardiac Imaging Cardiomed Tirgu Mures, Romania. The duration of the study is 2 years which include the initial screening and the follow-up period for the recurrence of AF.

The study will include 100 subjects suitable for catheter ablation. Imaging biomarkers and laboratory analyses such as high sensitive C Reactive Protein (hsCRP), matrix metalloproteases (MMP), interleukin-6 (IL6) and N-Terminal Pro-B-Type Natriuretic Peptide (NT pro-BNP) will be determined in the first 24 hours after the procedure. The anatomy of pulmonary veins, atrial fibrosis, atrial volumes and the amount of epicardial fat will be evaluated and quantified with late gadolinium-enhancement cardiac magnetic resonance (LGE-CMR). All these parameters will be investigated in patients with successful ablation of AF, who will be divided into 2 groups: group 1 - patients who develop AF recurrence at 1-year, and group 2 - patients with no recurrence of AF at 1-year. In all patients, the following biomarkers will be determined: serum levels of inflammatory biomarkers and NT-proBNP at 24 hours and 1 year post-procedure, the amount of myocardial fibrosis at the level of left atrium and left ventricle at baseline +/- 7 days and the amount of epicardial fat surrounding left atrium, right atrium and the entire heart at baseline +/- 7 days.

The study will be conducted over a period of 2 years, in which patients will be examined at baseline, and will be followed-up for recurrence of AF.

All patients will sign an informed written consent and will be checked for the exclusion criteria prior to enrolment.

Study objectives:

Primary: To investigate the correlation between imaging markers provided by cardiac magnetic resonance (including the degree of left atrial and ventricular fibrosis, left and right atrial volume, epicardial fat tissue volume), inflammatory biomarkers, and the risk of AF recurrence post ablation.

Secondary: To investigate the correlation between structural remodeling of the left and right atrium, epicardial fat tissue volume and serum inflammatory biomarkers in patients with AF.

Study Timeline:

  • Baseline (day 0)
  • Obtain and document consent from participant on study consent form.
  • Verify inclusion/exclusion criteria.
  • Obtain demographic information, medical history, medication history, alcohol, and tobacco use history.
  • Record results of physical examinations and 12-lead ECG.
  • Collect blood specimens (complete blood count, biochemistry and inflammatory biomarkers).
  • Imaging procedures: transthoracic 2-D echocardiography, late gadolinium-enhancement cardiac magnetic resonance
  • Visit 1 (month 1,3,6,12)
  • Record results of physical examinations, 12-lead ECG and medical history.
  • Imaging procedures: transthoracic 2-D echocardiography
  • Final study visit (month 12)
  • Record results of physical examinations, medical history,12-lead ECG and determination of serum levels of inflammatory biomarkers and NT-proBNP
  • Imaging procedures: transthoracic 2-D echocardiography
  • End-point evaluation.

Study procedures:

  • Medical history, clinical examination, laboratory tests (complete blood count, biochemistry, serum level of hs-CRP, MMP, IL6, and NT-pro-BNP);
  • 12-lead ECG
  • 2D transthoracic echocardiography with measurement of cardiac diameters, volumes, valvular function and regurgitation, pressure gradients, left ventricular systolic and diastolic function and ejection fraction.
  • Late Gadolinium-Enhancement Cardiac Magnetic Resonance (LGE-CMR) with the evaluation of left and right atrial volume, the volume of epicardial adipose tissue, the degree of atrial and ventricular fibrosis
  • Pulmonary vein isolation radiofrequency ablation with advanced 3D mapping system

Data collection: All the information will be collected in a database that consists of patient's background, medical history, medication, imaging features provided by cardiac ultrasound, Cardiac magnetic resonance and CMR imaging post-processing.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Romania
    • Mures
      • Targu Mures, Mures, Romania, 540102
        • Cardio Med Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Study population includes patients from a single center with paroxysmal and persistent atrial fibrillation, meeting inclusion and exclusion criteria and undergoing pulmonary vein isolation radiofrequency catheter ablation.

Description

Inclusion Criteria:

  • Patients with non-valvular paroxysmal or persistent atrial fibrillation who undergo successful ablation of atrial fibrillation, either by cryoablation or by radiofrequency advanced 3D mapping system;
  • Ability to provide informed consent;
  • Patients aged at least 18 years;

Exclusion Criteria:

  • Patients with valvular atrial fibrillation;
  • Patients with acute coronary syndrome in the last 30 days
  • Patients in whom atrial fibrillation is presumed to be caused by hyperthyreosis
  • Patients with long-standing persistent or permanent atrial fibrillation;
  • Unwillingness or incapacity to provide informed consent;
  • Allergy to gadolinium contrast media;
  • Absolute or relative contraindications to magnetic resonance imaging
  • Pregnancy or lactation;
  • Women with childbearing potential in absence of any contraceptive treatment
  • Renal insufficiency (creatinine greater than 1.5 mg/dL) or renal failure requiring dialysis;
  • Active malignancy or malignancy within the last 5 year prior to enrollment;
  • Conditions associated with an estimated life expectancy of under 2 years;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
AF-SG 01
Study subjects with atrial fibrillation recurrence after ablation: Blood sampling (assessment of complete blood count, biochemistry, inflammatory biomarkers), 2D transthoracic echocardiography, Late Gadolinium-Enhancement Cardiac Magnetic Resonance, and complex left and right atrium analysis, Pulmonary vein isolation radiofrequency ablation
Diagnostic test: Cardiac imaging tests
2D transthoracic echocardiography; Late gadolinium-enhancement cardiac magnetic resonance with the evaluation of pulmonary veins anatomy, atrial fibrosis, atrial volumes and the amount of epicardial fat will
Diagnostic test: Venous blood samle collection
Venous blood sample collection 1 day prior to the ablation procedure: Serum levels of high sensitive C Reactive Protein, Matrix metalloproteases, Interleukin-6, and N-Terminal Pro-B-Type Natriuretic Peptide.
AF-SG 02
Study subjects without atrial fibrillation recurrence after ablation: Blood sampling (assessment of complete blood count, biochemistry, inflammatory biomarkers), 2D transthoracic echocardiography, Late Gadolinium-Enhancement Cardiac Magnetic Resonance, and complex left and right atrium analysis, Pulmonary vein isolation radiofrequency ablation
Diagnostic test: Cardiac imaging tests
2D transthoracic echocardiography; Late gadolinium-enhancement cardiac magnetic resonance with the evaluation of pulmonary veins anatomy, atrial fibrosis, atrial volumes and the amount of epicardial fat will
Diagnostic test: Venous blood samle collection
Venous blood sample collection 1 day prior to the ablation procedure: Serum levels of high sensitive C Reactive Protein, Matrix metalloproteases, Interleukin-6, and N-Terminal Pro-B-Type Natriuretic Peptide.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The rate of AF recurrence after pulmonary vein isolation
Time Frame: 12 months
The primary outcome measure will be represented by the rate of AF recurrence at 1 year post ablation, documented by either ECG or Holter monitoring.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of re-hospitalization
Time Frame: 12 months
The secondary endpoints of the study will be: rate of re-hospitalization, rate of survival without relapse, rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke)
12 months
Rate of survival without relapse
Time Frame: 12 months
The secondary endpoints of the study will be: rate of re-hospitalization, rate of survival without relapse, rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke)
12 months
Rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke)
Time Frame: 12 months
The secondary endpoints of the study will be: rate of re-hospitalization, rate of survival without relapse, rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke)
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cardio Med Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Targu Mures, Romania
University Hospital of Targu Mures, Romania

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Szilamér Korodi, M.D., University of Medicine and Pharmacy of Tirgu Mures, Romania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 25, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CM0318-FIR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All IPD that underlie results in a publication will be available for interested parties.

IPD Sharing Time Frame

The IPD sharing frame is starting 6 months after publication.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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