Resynchronization in Patients With HF in AF Trial Undergoing Pace & AVNA Strategy With LBBAP Compared With BiV Pacing (RAFT-P&A)

Resynchronization in Patients With Ambulatory Heart Failure in Atrial Fibrillation Trial Undergoing Pace and Atrioventricular Node Ablation Strategy With Left Bundle Branch Area Pacing Compared With Biventricular Pacing

This trial will compare two management strategies for HF patients with Atrial Fibrillation. The active control group will undergo BiV pacing, followed by an AV node ablation. The experimental group will undergo LBBAP, followed by an AV node ablation.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Atrial Fibrillation; Cardiomyopathies
• Intervention / Treatment: Procedure: CRT; Procedure: AV node ablation; Procedure: Left Bundle Branch Area Pacing

Detailed Description

This is a prospective, randomized, double blind, control trial with follow up visits at 6- and 12-months following randomization. Patients will be randomized in a 1:1 allocation to either the control group [optimal medical therapy (OMT) + CRT + ANVA] or the treatment group [OMT + LBBAP + ANVA]. Randomization will be stratified by site and LVEF. In each group, the patient will undergo the pacing procedure (CRT or LBBAP) within 10 working days of randomization. They will be assessed by a physician one week after the CRT procedure, and if eligible, they will undergo an AVNA within 1-4 weeks. Success of these treatment plans will be evaluated primarily based on the change in NT-proBNP from baseline to 6- and 12-month follow ups. At baseline and follow up visits study staff and physicians will collect participants' medical history, complete a Physical Exam and an NYHA Class Assessment, a medication assessment, and a 6 Minute Walk Test. Participants will also be asked to complete Quality of Life Questionnaires (Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, KCCQ and EQ-5D-5L), have an ECG and TTE performed if they have not had one performed recently, non- invasive hemodynamic measurements (if available), and complete routine bloodwork and an NT-proBNP test. The adequacy of HF treatment will be assessed clinically, and medications optimized and recorded. Device diagnostics will be assessed and recorded as to whether there are arrhythmias and to determine the appropriateness of device programming. Secondary study outcomes include QoL scores (MLHFQ, KCCQ and EQ-5D), as well as 6MWT distance, and change in echocardiogram parameters (including change in LVESV index from baseline, change in global longitudinal LV systolic strain from baseline, and change in LVEF from baseline at 6-month and 12-month followup). Secondary outcomes also include radiation exposure between LBBAP and CRT, feasibility of achieving conduction system pacing with LBBAP compared to CRT, and acute and long-term hemodynamic change due to either CRT or LBBAP (i.e., non-invasive hemodynamic measurements before and after AV node ablation including systolic BP, diastolic BP, cardiac output, stroke volume, total peripheral resistance, and pulse pressure).

• Study Type: Interventional
• Enrollment (Anticipated): 284
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Abbie Barron; Phone Number: 86459 519-661-2111; Email: abbie.barron@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada
      • Recruiting
      • London Health Sciences Centre
      • Contact: Sabrina Wall; Phone Number: 34008 (519) 685-8500; Email: sabrina.wall@lhsc.on.ca
      • Principal Investigator: Habib Khan, MBBS, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with atrial fibrillation (AF) where AVNA is being considered with or without a pacemaker

   1. Are on optimal heart failure therapies for ≥4 weeks
   2. NYHA class I-IVa

2. Patients deemed not appropriate for rhythm control strategy (only for rate control strategy).

   1. Failed Ablation (≥1 failed ablation attempt)
   2. Refractory or intolerant to Antiarrhythmic drugs AADs or rate control medications
   3. Patient choice not to have rhythm control strategies
   4. Being considered for AVNA
3. Patients with baseline NT-proBNP>600 or >400 if HF hospitalization within 12 months.

Exclusion Criteria:

1. In-hospital patients with acute cardiac or non-cardiac illness that requires intensive care
2. Acute coronary syndrome (including MI) or Coronary revascularization (CABG or PCI) <3 months
3. Uncorrected or uncorrectable primary moderate to severe valvular disease
4. TAVI < 3 months
5. Restrictive, or reversible form of cardiomyopathy, cardiac amyloidosis
6. Severe primary pulmonary disease such as cor pulmonale, irreversible lung disease requiring inhalers, oxygen supplementation
7. Pulmonary hypertension (Mean pulmonary pressure is ≥35 mm Hg)
8. Patients with a life expectancy of less than one year from non-cardiac cause
9. Patients included in other clinical trials that will affect the objectives of this study or have competing interests
10. Those unable or unwilling to provide informed consent unless supported by legal power of attorney
11. Active malignancy with likelihood of survival <1 year
12. NYHA class IVb

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cardiac Resynchronization Therapy + AV node ablation; The active comparator group will be treated with CRT followed by an Atrioventricular Node Ablation.	Procedure: CRT; The patients will be allocated by randomization to receive the intervention of CRT.; Procedure: AV node ablation; AV node ablation after 4 weeks of CRT implant or LBBAP implant.
Experimental: Left Bundle Branch Area Pacing + AV node ablation; The experimental group will be treated with LBBAP followed by an Atrioventricular Node Ablation.	Procedure: AV node ablation; AV node ablation after 4 weeks of CRT implant or LBBAP implant.; Procedure: Left Bundle Branch Area Pacing; The patients will be allocated by randomization to receive the intervention of Left Bundle Branch Area Pacing; Other Names: LBBAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NT-proBNP from baseline to 6-month follow-up	Comparison between NT-proBNP measurement at baseline and 6-month follow-up	baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event rates of the composite outcome of heart failure events and all-cause mortality	HF and mortality data will be collected throughout the duration of the study	12 months
Change in QoL - MLHFQ	The Minnesota Living with Heart Failure Questionnaire (MLHFQ) score is used to measure quality of life. The MLHFQ consists of 21 questions answered on a 0-5 likert scale, with higher scores indicating a stronger impact of heart failure on QoL.	baseline, 6 months and 12 months
Change in QoL - KCCQ	Cardiomyopathy Questionnaire (Kansas City) (KCCQ-12) measures how heart failure impacts a patient's quality of life. The questionnaire measures frequency and burden of heart failure symptoms as well as physical and social limitations related to heart failure using a likert scale of 0-100, with higher scores indicating better health.	baseline, 6 months and 12 months
Change in QoL - EQ-5D	EuroQol- 5 Dimension measures health related quality of life using a Level 1-5 component scale. A lower score indicates better health related quality of life. The EQ-5D also contains the EQ VAS, a 0-100 self reported scale where 100 indicates best health imaginable.	baseline, 6 months and 12 months
Change 6MWT distance	Change in distance walked in the 6MWT from baseline to 6-month and 12-month follow-up	baseline, 6 months and 12 months
Change in echocardiogram parameters - Left Ventricular End Systolic Volume index (LVESVi)	Compared from baseline to 6-month and 12-month follow-up. A lower LVESVi indicates a trend towards normal volumes and a higher LVESVi indicates ventricle dilation compared to the normal population.	baseline, 6 months and 12 months
Change in echocardiogram parameters - Left Ventricle (LV) Global Longitudinal strain	Compared from baseline to 6-month and 12-month follow-up. A lower LV Global Longitudinal strain indicates stronger left ventricular contraction.	baseline, 6 months and 12 months
Change in echocardiogram parameters - Left Ventricular Ejection Fraction (LVEF)	Compared from baseline to 6-month and 12-month follow-up. An increase in LVEF indicates stronger function of the left ventricle.	baseline, 6 months and 12 months
Radiation exposure at device implant	Exposure time collected at device implant visits	During Surgical Intervention

Collaborators and Investigators

• Sponsor: Habib Khan
• Collaborators: London Health Sciences Centre
• Investigators: Principal Investigator: Habib Khan, MBBS, PhD, London Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 14, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: atrial fibrillation; CRT; AV node ablation; LBBAP; Conductions system pacing; pace and ablate; BiV-CRT
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Failure; Atrial Fibrillation; Cardiomyopathies
• Other Study ID Numbers: 3819

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: No
• Studies a U.S. FDA-regulated device product: No