Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure (TAP-CHF)

• ClinicalTrials.gov Identifier: NCT04160000
• Recruitment Status: Not yet recruiting
• First Posted: November 12, 2019
• Last Update Posted: July 24, 2020
• Sponsor: Electrophysiology Research Foundation
• Information provided by (Responsible Party): Electrophysiology Research Foundation

Study Description

Brief Summary:

This is a prospective randomized comparative evaluation of catheter ablation and rate or rhythm control drug therapy for safety and efficacy in in patients with atrial fibrillation and one or more HF events with preserved systolic cardiac function. This study is a randomized, open label, active-controlled trial with an open-label safety extension, designed to compare a composite clinical outcomes endpoint of heart failure hospitalizations and cardiovascular mortality among patients randomized to catheter ablation or rate or rhythm control drug therapy.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Heart Failure; Diastolic Heart Failure	Device: Catheter ablation; Drug: Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation	Phase 4

Detailed Description:

This study is a randomized, open label, active-controlled trial with an open-label safety extension, designed to compare a composite clinical outcomes endpoint of heart failure hospitalizations and cardiovascular mortality in patients with atrial fibrillation with heart failure with preserved systolic function. The will be randomized to catheter ablation or Rate or Rhythm control drug therapy. This is an open label two phase study in which patients will be randomized in a 1:1 ratio to receive catheter ablation or rate or rhythm control drug therapy. The pilot phase will consist to 60 patients .They will be followed for a minimum of 6 months for safety and efficacy. The main trial will enroll 360 patients at 20 centers and they will be followed for a minimum of 12 months. Pilot phase patients will be followed in the main trial. Drug transitions will be performed according to approved drug labeling.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study is a randomized, open label, active-controlled trial with an open-label safety extension, designed to compare a composite clinical outcomes endpoint of cardiovascular hospitalizations and survival among patients randomized to catheter ablation or rate or rhythm control drug therapy. This is an open label two phase study in which patients will be randomized in a 1:1 ratio to receive catheter ablation or rate or rhythm control drug therapy.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: October 1, 2020
• Estimated Primary Completion Date: March 31, 2022
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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 12 months after the catheter ablation 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; Other Name: Ablation
Active Comparator: Antiarrhythmic drug therapy; Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent. They randomly assigned to antiarrhythmic drug therapy for Rate or Rhythm control as one arm. They will undergo drug dose titration within 14 days of randomization. This procedure will include isolation of all four pulmonary veins in the antrum using catheter delivered radiofrequency current, cryoballoon or laser balloon ablation with standard FDA approved ablation catheter systems used in atrial fibrillation ablation. Patients will be monitored for a minimum period of 12 months after the catheter ablation intervention.	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; Other Name: Antiarrhythmic Drug

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   Time to either first of Heart failure hospitalization and/or mortality due to cardiovascular etiology

Secondary Outcome Measures :

1. All cause Mortality [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 12 months ]
   Time to mortality due to any cause
2. MACE events [ Time Frame: From date of randomization until the date of first documented major adverse cardiovascular event, assessed up to 12 months ]
   Time to major adverse cardiovascular event
3. Cardiovascular Hospitalization [ Time Frame: From date of randomization until the date of first documented hospitalization due to cardiovascular causes , assessed up to 12 months ]
   Time to first hospitalization due to cardiovascular causes

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: SANJEEV SAKSENA, MD; 7323029990 ext 7323029990; cmenj@aol.com

Contact: Carine Carvalhiero, BS; 7323029990 ext 7323029990; eprf@aol.com

Locations

United States, New Jersey

Electrophysiology Research Foundation

Warren, New Jersey, United States, 07059

United States, Texas

TCAI at St. David's Hospital

Austin, Texas, United States, 78705

Contact: Andrea Natale, MD dr.natale@gmail.com

Contact: Sangamitra Mohanty, MBBS Mitra.Mohanty@stdavidsintl.com

Sponsors and Collaborators

Electrophysiology Research Foundation

Investigators

• Study Chair: Sanjeev Saksena, MD; Electrophysiology Research Foundation
• Study Director: Andrea Natale, MD; Electrophysiology Research Foundation

More Information

Publications:

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. Review.

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.

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.

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.

• Responsible Party: Electrophysiology Research Foundation
• ClinicalTrials.gov Identifier: NCT04160000
• Other Study ID Numbers: EPRF - 2019 - 11
• First Posted: November 12, 2019
• Last Update Posted: July 24, 2020
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Electrophysiology Research Foundation:

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

Additional relevant MeSH terms:

Heart Failure; Atrial Fibrillation; Heart Failure, Diastolic; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Anti-Arrhythmia Agents