Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure

Heart Failure Clinical Trial

— TAP-CHF  

Official title:

A Phase 4, Randomized, Open Label, Multicenter Prospective Comparative Study To Evaluate The Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04160000
• Other study ID #: EPRF - 2019 - 11
• Status: Recruiting
• Phase: Phase 4
• Start date: July 26, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: Electrophysiology Research Foundation
• Contact: SANJEEV SAKSENA, MD
• Phone: 7323029990
• Email: cmenj[@]aol.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Diastolic Heart Failure
• Heart Failure
• Heart Failure, Diastolic

Intervention

Device:
• 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

Drug:
• 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

Device:
• Insertion of CardioMems Hemodynamic monitor
Insertion of wireless hemodynamic monitor to provide hemodynamic data to guide heart failure therapy to achieve heart failure improvement.

Drug:
• Empiric heart failure drug therapy
Administration of heart failure drug therapy based on clinical evaluation to achieve heart failure improvement.

Locations

Country	Name	City	State
Germany	Peter Osypka Herzzentrum	Munich	Bavaria
Switzerland	Hopitaux Universitaires de Geneve	Geneva	Geneve
United States	TCAI at St. David's Hospital	Austin	Texas
United States	Northern Arizona Health Care	Flagstaff	Arizona
United States	St. Bernards Heart and Vascular Center	Jonesboro	Arkansas
United States	South Denver Cardiology	Littleton	Colorado
United States	Kansas City Heart Rhythm Institute	Overland	Missouri
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Electrophysiology Research Foundation	Warren	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Electrophysiology Research Foundation

Countries where clinical trial is conducted

United States,  Germany,  Switzerland, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	All cause Mortality	Time to mortality due to any cause	From date of randomization until the date of death from any cause, assessed up to 12 months
Secondary	MACE events	Time to major adverse cardiovascular event	From date of randomization until the date of first documented major adverse cardiovascular event, assessed up to 12 months
Secondary	Cardiovascular Hospitalization	Time to first hospitalization due to cardiovascular causes	From date of randomization until the date of first documented hospitalization due to cardiovascular causes , assessed up to 12 months