Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure

NCT ID: NCT04160000

Last Updated: 2024-05-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-26

Study Completion Date

2025-06-30

Brief Summary

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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.

Detailed Description

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This is a prospective pilot study utilizing a randomized comparative sequential evaluation of these two therapeutic approaches in two consecutive phases:

Phase 1 will examine an initial catheter ablation strategy versus an initial antiarrhythmic drug (AAD) therapy strategy for safety and efficacy in patients with atrial fibrillation with preserved systolic cardiac function, heart failure hospitalization in the past year or one or more documented HF events.

Phase 2 will examine optimized rhythm control therapy with and without wireless pulmonary artery pressure hemodynamic monitoring for HF therapy optimization in the same patients as in Phase 1 with documented atrial fibrillation with preserved systolic cardiac function, prior HF hospitalization and class III heart failure.

This is an open label two phase study in which patients will be randomized in a 1:1 ratio to either ablation or AAD with a pilot phase 1 that will consist to 100 patients enrolled at 10 centers. They will be followed for a minimum of 6 months, after a three month blanking period, for event rates of the primary endpoint as well as safety and efficacy. Phase 2 will randomize patients completing Phase 1 to hemodynamic monitoring with a wireless pulmonary artery sensor insertion and guided HF therapy or empiric standard of care HF therapy. They will be followed for a minimum of 6 months, after a three month blanking period for optimization of rhythm and HF therapies.

This study is a sequential randomized, open label, active-controlled trial, designed to compare a composite clinical outcomes endpoint of heart failure hospitalization and/or cardiovascular mortality among these patients randomized to each of these treatment strategies. This endpoint will be employed in both pilot trial phases to assess event rates, as well as safety endpoints. This data will form the basis of a larger pivotal trial

Conditions

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Atrial Fibrillation Heart Failure Diastolic Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a prospective pilot study utilizing a randomized comparative sequential evaluation of two therapeutic approaches in two consecutive phases. Phase 1 will examine an initial catheter ablation strategy versus an initial antiarrhythmic drug (AAD) therapy strategy for safety and efficacy in patients with atrial fibrillation with preserved systolic cardiac function, heart failure hospitalization in the past year or one or more documented HF events.

Phase 2 will examine optimized rhythm control therapy with and without wireless pulmonary artery pressure hemodynamic monitoring for HF therapy optimization in the same patients as in Phase 1 with documented atrial fibrillation with preserved systolic cardiac function, prior HF hospitalization and class III heart failure.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Catheter ablation

Intervention Type DEVICE

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

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

Group Type ACTIVE_COMPARATOR

Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Insertion of CardioMems Hemodynamic monitor

Intervention Type DEVICE

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

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

Group Type ACTIVE_COMPARATOR

Empiric heart failure drug therapy

Intervention Type DRUG

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

Interventions

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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

Intervention Type DEVICE

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

Intervention Type DRUG

Insertion of CardioMems Hemodynamic monitor

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

Intervention Type DEVICE

Empiric heart failure drug therapy

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

Intervention Type DRUG

Other Intervention Names

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Ablation Antiarrhythmic Drug IPM HFDrug

Eligibility Criteria

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Inclusion 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.
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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Electrophysiology Research Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sanjeev Saksena, MD

Role: STUDY_CHAIR

Electrophysiology Research Foundation

Andrea Natale, MD

Role: STUDY_DIRECTOR

Electrophysiology Research Foundation

Locations

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Northern Arizona Health Care

Flagstaff, Arizona, United States

Site Status RECRUITING

St. Bernards Heart and Vascular Center

Jonesboro, Arkansas, United States

Site Status RECRUITING

South Denver Cardiology

Littleton, Colorado, United States

Site Status RECRUITING

Kansas City Heart Rhythm Institute

Overland, Missouri, United States

Site Status RECRUITING

Electrophysiology Research Foundation

Warren Township, New Jersey, United States

Site Status RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

TCAI at St. David's Hospital

Austin, Texas, United States

Site Status RECRUITING

Peter Osypka Herzzentrum

Munich, Bavaria, Germany

Site Status NOT_YET_RECRUITING

Hopitaux Universitaires de Geneve

Geneva, Canton of Geneva, Switzerland

Site Status RECRUITING

Countries

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United States Germany Switzerland

Central Contacts

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SANJEEV SAKSENA, MD

Role: CONTACT

7323029990 ext. 7323029990

Carine Carvalhiero, BS

Role: CONTACT

7323029990 ext. 7323029990

Facility Contacts

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Paula McAllister

Role: primary

928-214-3616

Devi G Nair, MD

Role: primary

Sydney Stevens, NP

Role: backup

Sri Sundaram, MD

Role: primary

Mary Soltau, MSN

Role: backup

Dhananjaya R Lakkireddy, MD

Role: primary

Jennifer Bush, MSN

Role: backup

Sanjeev Saksena, MBBS MD

Role: primary

732-302-9988

Carine Carvalheiro

Role: backup

732-302-9990

Mathew D Hyman, MD

Role: primary

Mary Gnap

Role: backup

Andrea Natale, MD

Role: primary

Sangamitra Mohanty, MBBS

Role: backup

Thorsten Lewalter, MD

Role: primary

Clemens Jilek, MD

Role: backup

Dipen Shah, MD

Role: primary

Luca Galbiati, MD

Role: backup

References

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Saksena S, Slee A. Atrial fibrillation and its pernicious role in heart failure with preserved ejection fraction: a new frontier in interventional electrophysiology. J Interv Card Electrophysiol. 2018 Mar;51(2):89-90. doi: 10.1007/s10840-018-0341-3. No abstract available.

Reference Type BACKGROUND
PMID: 29480345 (View on PubMed)

Cikes M, Claggett B, Shah AM, Desai AS, Lewis EF, Shah SJ, Anand IS, O'Meara E, Rouleau JL, Sweitzer NK, Fang JC, Saksena S, Pitt B, Pfeffer MA, Solomon SD. Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial. JACC Heart Fail. 2018 Aug;6(8):689-697. doi: 10.1016/j.jchf.2018.05.005. Epub 2018 Jul 11.

Reference Type BACKGROUND
PMID: 30007557 (View on PubMed)

Slee A, Saad M, Saksena S. Heart failure progression and mortality in atrial fibrillation patients with preserved or reduced left ventricular ejection fraction. J Interv Card Electrophysiol. 2019 Sep;55(3):325-331. doi: 10.1007/s10840-019-00534-x. Epub 2019 Mar 18.

Reference Type BACKGROUND
PMID: 30887281 (View on PubMed)

Slee A, Saksena S. Impact of initial heart failure emergence on clinical outcomes of atrial fibrillation patients in the AFFIRM trial. Am Heart J. 2020 Feb;220:1-11. doi: 10.1016/j.ahj.2019.10.005. Epub 2019 Oct 28.

Reference Type BACKGROUND
PMID: 31756389 (View on PubMed)

Other Identifiers

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EPRF - 2019 - 11

Identifier Type: -

Identifier Source: org_study_id

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