Heart Failure Clinical Trial

Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure

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.

View Full Description

Full Description

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

View Eligibility Criteria

Eligibility Criteria

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

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.
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
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.

Exclusion Criteria:

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
Patients with other clinically significant medical condition that precludes study participation
Patients with life expectancy < 1 year
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.
Pregnant or nursing lactating mothers or women of childbearing potential who are not on effective contraceptive therapy
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 is for people with:

Heart Failure

Phase:

Phase 4

Estimated Enrollment:

360

Study ID:

NCT04160000

Recruitment Status:

Recruiting

Sponsor:

Electrophysiology Research Foundation

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There are 9 Locations for this study

See Locations Near You

Northern Arizona Health Care
Flagstaff Arizona, 86001, United States More Info
Paula McAllister
Contact
928-214-3616
[email protected]
Rangadham Nagarakanti
Principal Investigator
St. Bernards Heart and Vascular Center
Jonesboro Arkansas, 72401, United States More Info
Devi G Nair, MD
Contact
[email protected]
Sydney Stevens, NP
Contact
South Denver Cardiology
Littleton Colorado, 80120, United States More Info
Sri Sundaram, MD
Contact
[email protected]
Mary Soltau, MSN
Contact
[email protected]
Kansas City Heart Rhythm Institute
Overland Missouri, 66211, United States More Info
Dhananjaya R Lakkireddy, MD
Contact
[email protected]
Jennifer Bush, MSN
Contact
[email protected]
Rakesh Gopinathannair, MD
Sub-Investigator
Electrophysiology Research Foundation
Warren New Jersey, 07059, United States More Info
Sanjeev Saksena, MBBS MD
Contact
732-302-9988
[email protected]
Carine Carvalheiro
Contact
732-302-9990
Sanjeev Saksena, MD
Principal Investigator
Atul Prakash, MD
Sub-Investigator
Hospital of the University of Pennsylvania
Philadelphia Pennsylvania, 19104, United States More Info
Mathew D Hyman, MD
Contact
[email protected]
Mary Gnap
Contact
[email protected]
TCAI at St. David's Hospital
Austin Texas, 78705, United States More Info
Andrea Natale, MD
Contact
[email protected]
Sangamitra Mohanty, MBBS
Contact
[email protected]
Mary B Cishek, MD
Sub-Investigator
Peter Osypka Herzzentrum
Munich Bavaria, 81379, Germany More Info
Thorsten Lewalter, MD
Contact
[email protected]
Clemens Jilek, MD
Contact
[email protected]
Hopitaux Universitaires de Geneve
Geneva Geneve, 1205, Switzerland More Info
Dipen Shah, MD
Contact
[email protected]
Luca Galbiati, MD
Contact
[email protected]

How clear is this clinincal trial information?

Study is for people with:

Heart Failure

Phase:

Phase 4

Estimated Enrollment:

360

Study ID:

NCT04160000

Recruitment Status:

Recruiting

Sponsor:


Electrophysiology Research Foundation

How clear is this clinincal trial information?

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