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

October 18, 2022 updated by: Electrophysiology Research Foundation

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Anticipated)

360

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: SANJEEV SAKSENA, MD
  • Phone Number: 7323029990 7323029990
  • Email: cmenj@aol.com

Study Contact Backup

  • Name: Carine Carvalhiero, BS
  • Phone Number: 7323029990 7323029990
  • Email: eprf@aol.com

Study Locations

  • Germany
  • Switzerland
  • United States
    • Arizona
    • Arkansas
      • Jonesboro, Arkansas, United States, 72401
        • Recruiting
        • St. Bernards Heart and Vascular Center
        • Contact:
        • Contact:
          • Sydney Stevens, NP
    • Colorado
    • Missouri
      • Overland, Missouri, United States, 66211
    • New Jersey
      • Warren, New Jersey, United States, 07059
        • Recruiting
        • Electrophysiology Research Foundation
        • Contact:
          • Sanjeev Saksena, MBBS MD
          • Phone Number: 732-302-9988
          • Email: eprf@aol.com
        • Contact:
          • Carine Carvalheiro
          • Phone Number: 732-302-9990
        • Principal Investigator:
          • Sanjeev Saksena, MD
    • Pennsylvania
    • Texas
      • Austin, Texas, United States, 78705

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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 Names:
  • Ablation
Active Comparator: 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
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 Names:
  • Antiarrhythmic Drug
Active Comparator: 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
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.
Other Names:
  • IPM
Active Comparator: 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
Drug: Empiric heart failure drug therapy
Administration of heart failure drug therapy based on clinical evaluation to achieve heart failure improvement.
Other Names:
  • HFDrug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From date of randomization until the date of death from any cause, assessed up to 12 months
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
From date of randomization until the date of first documented major adverse cardiovascular event, assessed up to 12 months
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
From date of randomization until the date of first documented hospitalization due to cardiovascular causes , assessed up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Electrophysiology Research Foundation

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2020

Primary Completion (Anticipated)

March 31, 2024

Study Completion (Anticipated)

June 30, 2025

Study Registration Dates

First Submitted

November 6, 2019

First Submitted That Met QC Criteria

November 8, 2019

First Posted (Actual)

November 12, 2019

Study Record Updates

Last Update Posted (Actual)

October 19, 2022

Last Update Submitted That Met QC Criteria

October 18, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPRF - 2019 - 11

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure

Clinical Trials on Catheter ablation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malta

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe