Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure

NCT04160000 | Recruiting Phase 4 DMC FDA Drug FDA Device

• 1 other identifier: EPRF - 2019 - 11
• Study Type: interventional
• Target: 360
• Locations: 3 countries
• Sites: 9

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Time to Composite of Heart failure hospitalizations and/or Cardiovascular mortality

  Time to either first of Heart failure hospitalization and/or mortality due to cardiovascular etiology

  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

Secondary Outcomes (3)

• All cause Mortality

  From date of randomization until the date of death from any cause, assessed up to 12 months

• MACE events

  From date of randomization until the date of first documented major adverse cardiovascular event, assessed up to 12 months

• Cardiovascular Hospitalization

  From date of randomization until the date of first documented hospitalization due to cardiovascular causes , assessed up to 12 months

Study Arms (4)

Phase 1 Catheter Ablation

ACTIVE COMPARATOR

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.

Device: Catheter ablation

Phase 1 Antiarrhythmic drug therapy

ACTIVE COMPARATOR

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

Drug: Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation

Phase 2 Guided Heart Failure Therapy

ACTIVE COMPARATOR

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

Device: Insertion of CardioMems Hemodynamic monitor

Phase 2 Empiric Heart Failure Therapy

ACTIVE COMPARATOR

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

Drug: Empiric heart failure drug therapy

Interventions

Catheter ablation 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

Also known as: Ablation

Phase 1 Catheter Ablation

Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation DRUG

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

Also known as: Antiarrhythmic Drug

Phase 1 Antiarrhythmic drug therapy

Insertion of CardioMems Hemodynamic monitor DEVICE

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

Also known as: IPM

Phase 2 Guided Heart Failure Therapy

Empiric heart failure drug therapy DRUG

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

Also known as: HFDrug

Phase 2 Empiric Heart Failure Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be willing and able to give written informed consent
• 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.
• 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
• Written informed consent for the clinically indicated study procedures
• 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.

You may not qualify if:

• 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
• Patients with QRS duration of \>120 ms and intraventricular conduction defects who are or maybe candidates for or have received ventricular resynchronization therapy
• Recent (\<1 month) myocardial infarction or acute coronary syndrome
• Recent (\<3 months) coronary revascularization procedures
• Documented LA thrombus on TEE or any LVEF measurement \<40%
• Patients who are not candidates for Rate or Rhythm control drug therapy for AF
• Dilated cardiomyopathy due to potentially reversible cause e.g. myocarditis
• Contraindications to anticoagulant therapy or adverse event with prior Warfarin or DOAC therapy
• Creatinine clearance \<30ml/min or \>95ml/min
• 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
• Recent stroke (\<3 months) or thromboembolic event, transient ischemic attack or carotid angioplasty in the prior 3 months
• Recent (\<3 months) intracranial or other major bleeding event
• Candidates for heart or any other organ transplantation or left ventricular assist devices, recent (\< 3 months) valve or other cardiac surgery
• Patients requiring ACE inhibitor or ARB drug therapy for any reason
• History of hypersensitivity to antiarrhythmic drugs

Sponsors & Collaborators

• Electrophysiology Research Foundation: lead

Study Sites (9)

Northern Arizona Health Care

Flagstaff, Arizona, 86001, United States

RECRUITING

St. Bernards Heart and Vascular Center

Jonesboro, Arkansas, 72401, United States

RECRUITING

South Denver Cardiology

Littleton, Colorado, 80120, United States

RECRUITING

Kansas City Heart Rhythm Institute

Overland, Missouri, 66211, United States

RECRUITING

Electrophysiology Research Foundation

Warren Township, New Jersey, 07059, United States

RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

TCAI at St. David's Hospital

Austin, Texas, 78705, United States

RECRUITING

Peter Osypka Herzzentrum

Munich, Bavaria, 81379, Germany

NOT YET RECRUITING

Hopitaux Universitaires de Geneve

Geneva, Canton of Geneva, 1205, Switzerland

RECRUITING

Related Publications (4)

• 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.

  PMID: 29480345 BACKGROUND

• 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.

  PMID: 30007557 BACKGROUND

• 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.

  PMID: 30887281 BACKGROUND

• 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.

  PMID: 31756389 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Heart Failure; Heart Failure, Diastolic

Interventions

Catheter Ablation; Anti-Arrhythmia Agents

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiofrequency Ablation; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Sanjeev Saksena, MD

  Electrophysiology Research Foundation

  STUDY CHAIR

• Andrea Natale, MD

  Electrophysiology Research Foundation

  STUDY DIRECTOR

Central Study Contacts

SANJEEV SAKSENA, MD

CONTACT

7323029990; cmenj@aol.com

Carine Carvalhiero, BS

CONTACT

7323029990; eprf@aol.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 12, 2019
• Study Start: July 26, 2020
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); CH (1); US (7)