Recruiting

Atrial Fibrillation

Sponsor:

Electrophysiology Research Foundation

Code:

NCT04160000

Conditions

Atrial Fibrillation

Heart Failure

Diastolic Heart Failure

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Catheter ablation

Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation

Insertion of CardioMems Hemodynamic monitor

Empiric heart failure drug therapy

Study Details

Brief summary:

Heart failure (HF) with preserved left ventricular function (pEF) is difficult clinical syndrome to treat effectively with few evidence based therapies. Atrial fibrillation (AF) is now an important co-morbidity being observed in 43% of patients with HFpEF. Rhythm control has not been studied in this population. Catheter ablation and antiarrhythmic drugs are rhythm control therapies that have been used for treatment of AF without HF or HF with reduced systolic function but have not been widely applied in HFpEF. No controlled comparative evaluation has been performed in HFpEF.

The introduction of wireless pulmonary artery hemodynamic monitoring has permitted optimization of HF therapy in patients with chronic HF with reduced and preserved EF. Reduction in HF hospitalizations has been observed in post hoc analyses of HFpEF patients but has not been systematically applied in AF patients with HFpEF.

In this study, we propose to study both rhythm control and optimized HF therapeutic approaches in an AF with HFpEF study population in a pilot study using a sequential two phase randomized controlled clinical trial design.

Conditions

Atrial Fibrillation

Heart Failure

Diastolic Heart Failure

Study ID

NCT04160000

Start date

Jul 26, 2020

Status verified date

May, 2024

Completion date

Jun 30, 2025

Anticipated

Primary completion date

Dec 31, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria: Patient with symptomatic Heart Failure with preserved systolic cardiac function \& paroxysmal or persistent atrial fibrillation who meet the following criteria

1. Subjects must be willing and able to give written informed consent
2. Outpatients ≥ 50 years of age, male or post- menopausal female patients; premenopausal female patients who are on and will maintain continuous birth control therapy during the study.
3. Subjects must have documented HFpEF \& paroxysmal or persistent AF and satisfy one of the following inclusion criteria a) Consecutive patients with AF, symptomatic heart failure requiring diuretic therapy for at least 30 days prior to study entry b) Hospitalization for HF and/or AF in the past 12 months prior to catheter ablation with documented NT-pro BNP >200pg/ml for patients not in AF or > 600 pg/ml for patients in AF on screening ECG or NYHA class 2, 3 or ambulatory class 4 heart failure documented NT-pro BNP >300pg/ml for patients not in AF or > 900 pg/ml for patients in AF on screening ECG c).Evidence of structural heart disease defined as by at least 1 of the following echocardiography findings (any local measurement made during the screening epoch or within the 6 months prior to screening visit): 1) LA enlargement defined by at least 1 of the following: LA width (diameter) >3.8 cm or LA length >5.0 cm or LA area >20 cm2 or LA volume >55 ml or LA volume index >29 ml/m2 2) LVH defined by septal thickness or posterior wall thickness >1.1 cm d).Left ventricular ejection fraction > 45% using standard imaging techniques at enrollment for study or in prior 6 months e).ECG documented paroxysmal or persistent atrial fibrillation f).Patients are candidates for a clinically indicated catheter ablation procedure, and Rate or Rhythm control antiarrhythmic drug therapy
4. Patients should be on one or more standard heart failure drug therapy (ies) for heart failure with preserved cardiac function for at least 30 days
5. Written informed consent for the clinically indicated study procedures
6. Patients must be candidates for long-term OAC therapy based on clinical practice guidelines for treatment of AF. Guidelines for GFR as established for DOACSs will be applicable to all subjects.

Exclusion Criteria:

1. Patients with HFpEF who were not on any drug therapy for HF or have uncontrolled hypertension defined as systolic BP >180 mm Hg at screening or >150 mm Hg on three or more antihypertensive drugs
2. Patients with QRS duration of >120 ms and intraventricular conduction defects who are or maybe candidates for or have received ventricular resynchronization therapy
3. Recent (<1 month) myocardial infarction or acute coronary syndrome
4. Recent (<3 months) coronary revascularization procedures
5. Documented LA thrombus on TEE or any LVEF measurement <40%
6. Patients who are not candidates for Rate or Rhythm control drug therapy for AF
7. Dilated cardiomyopathy due to potentially reversible cause e.g. myocarditis
8. Contraindications to anticoagulant therapy or adverse event with prior Warfarin or DOAC therapy
9. Creatinine clearance <30ml/min or >95ml/min
10. Advanced hepatic disease, pulmonary disease clinically significant congenital heart disease, clinically significant pericardial constriction, hypertrophic cardiomyopathy, infiltrative cardiomyopathy, decompensated valvular heart disease likely to require surgical or percutaneous intervention during the trial
11. Recent stroke (<3 months) or thromboembolic event, transient ischemic attack or carotid angioplasty in the prior 3 months
12. Recent (<3 months) intracranial or other major bleeding event
13. Candidates for heart or any other organ transplantation or left ventricular assist devices, recent (< 3 months) valve or other cardiac surgery
14. Patients requiring ACE inhibitor or ARB drug therapy for any reason
15. History of hypersensitivity to antiarrhythmic drugs
16. Patients with other clinically significant medical condition that precludes study participation
17. Patients with life expectancy < 1 year
18. Premenopausal female patients, who are not on continuous birth control therapy or are likely to discontinue it at any time during the entire duration of study enrollment.
19. Pregnant or nursing lactating mothers or women of childbearing potential who are not on effective contraceptive therapy
20. Patients who have been noncompliant with medical regimens or have social or other issues precluding regular follow up, history of alcohol or drug abuse in past 12 months.

Study Design

Enrollment

360 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Phase 1 Catheter Ablation

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent. They randomly assigned to catheter ablation as one arm. They will undergo a catheter ablation procedure within 14 days of randomization. This procedure will include isolation of all four pulmonary veins in the antrum using catheter delivered radiofrequency current, cryothermal or laser ablation energy with standard FDA approved ablation catheter systems used in atrial fibrillation ablation. Patients will be monitored for a minimum period of 9 months after the catheter ablation intervention.

active comparator: Phase 1 Antiarrhythmic drug therapy

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent. They will be randomly assigned to antiarrhythmic drug therapy for Rate or Rhythm control in this arm. They will undergo drug dose titration within 14 days of randomization. . Patients will be monitored for a minimum period of 9 months after the AAD therapy initiation

active comparator: Phase 2 Guided Heart Failure Therapy

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent and completion of Phase 1. They will be randomly assigned to insertion of an implantable hemodynamic monitor in this arm and heart failure therapy guided by wireless hemodynamic monitoring. Patients will be monitored for a minimum period of 9 months after the implantable hemodynamic monitor insertion on guided drug therapy

active comparator: Phase 2 Empiric Heart Failure Therapy

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent and completion of Phase 1. They will be randomly assigned to heart failure management with empirical selection of heart failure therapy. Patients will be monitored for a minimum period of 9 months after the initiation of empirically selected heart failure drug therapy

Interventions

Catheter ablation

Delivery of physical energy from external energy source via percutaneously inserted electrophysiologic catheter to destroy heart tissue in the human atrium and adjoining vasculature

Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation

Administration of antiarrhythmic drug to achieve either rate control or restoration of sinus rhythm for management of atrial fibrillation

Insertion of CardioMems Hemodynamic monitor

Insertion of wireless hemodynamic monitor to provide hemodynamic data to guide heart failure therapy to achieve heart failure improvement.

Empiric heart failure drug therapy

Administration of heart failure drug therapy based on clinical evaluation to achieve heart failure improvement.

Primary outcome measure

  • Time to Composite of Heart failure hospitalizations and/or Cardiovascular mortality [ Time Frame: From date of randomization until the date of first documented heart failure hospitalization or date of death from cardiovascular causes, whichever came first, assessed up to 12 months ]

Central Contacts and Locations

Central contacts

SANJEEV SAKSENA, MD

7323029990cmenj@aol.com

Carine Carvalhiero, BS

7323029990eprf@aol.com

Locations

Northern Arizona Health Care

Recruiting

Flagstaff, Arizona, United States, 86001

Contacts

Principal Investigator:

Rangadham Nagarakanti

St. Bernards Heart and Vascular Center

Recruiting

Jonesboro, Arkansas, United States, 72401

Contacts

Devi G Nair, MD

dr.devignair@gmail.com

South Denver Cardiology

Recruiting

Littleton, Colorado, United States, 80120

Contacts

Sri Sundaram, MD

sris@southdenver.com

Mary Soltau, MSN

msoltau@southdenver.com

Kansas City Heart Rhythm Institute

Recruiting

Overland, Missouri, United States, 66211

Contacts

Dhananjaya R Lakkireddy, MD

dlakkireddy@gmail.com

Electrophysiology Research Foundation

Recruiting

Warren, New Jersey, United States, 07059

Contacts

Sanjeev Saksena, MBBS MD

732-302-9988eprf@aol.com

Carine Carvalheiro

732-302-9990

Principal Investigator:

Sanjeev Saksena, MD

Hospital of the University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

TCAI at St. David's Hospital

Recruiting

Austin, Texas, United States, 78705

Contacts

Andrea Natale, MD

dr.natale@gmail.com

Sangamitra Mohanty, MBBS

Mitra.Mohanty@stdavidsintl.com

More Information

Sponsor

Electrophysiology Research Foundation

Last update posted

May 23, 2024

Last verified

May, 2024

Keywords

  • Atrial fibrillation
  • Heart failure
  • Diastolic heart failure
  • Catheter Ablation
  • Antiarrhythmic Drugs

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Electrophysiology Research Foundation on 2024-05-23.