RAFT-P&A Randomized Control Trial

Resynchronization for Ambulatory Heart Failure Trial in Patients With Chronic Atrial Fibrillation - Pharmacological Rate Control vs. Pace and Ablate With Bi-Ventricular or Conduction System Pacing

Atrial fibrillation (AF) is an irregular heartbeat that can cause symptoms of skipped beats, shortness of breath, stroke, or in some cases fluid in the lungs or legs. Treating AF is mostly to do with slowing the heart rate down so that the heart can get a chance to regain some energy. In some cases, slowing the heart rate is not easy to achieve as some elderly patients find it difficult to tolerate medications and suffer the side effects of such treatments. In those instances, there might be a possibility to permanently control the heart rate by implanting a pacemaker in the heart and intentionally damaging a regulatory region of the heart called the atrioventricular (AV) node. Damaging the AV node by a procedure called ablation results in the AF not being able to influence the bottom chambers (the ventricles) resulting in a slow rhythm. Therefore, if a pacemaker is implanted then the heart rate can be completely regulated by the pacemaker.

A complex pacemaker that stimulates both the right and left ventricles simultaneously (BiVP) has been used for the last decade prior to AV node ablation. More recently, a technique has been designed to reduce the number of leads in the heart, reduce procedure time and have a similar effect on the heart called Conduction System Pacing (CSP). However, this has not been directly compared to BiVP in a robust randomized control trial. There is also not enough existing evidence to show that a pace and ablate strategy is superior to optimal medical therapy. We intend to compare the efficacy of BiVP to CSP in patients who undergo AV node ablation for treating AF, in addition to comparing both pace and ablate methods to pharmacological therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Atrial Fibrillation; Pacemaker; Arrhythmia Atrial
• Intervention / Treatment: Drug: Medication; Device: Pace and Ablate

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Habib R Khan, MBBS, PhD; Phone Number: 519-6633746; Email: habib.khan@lhsc.on.ca
• Study Contact Backup: Name: Abbie Pardo; Email: abbie.pardo@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • London Health Sciences Centre - University Hospital
    • London, Ontario, Canada, N6G5A5
      • London Health Sciences Research
      • Contact: Abbie Pardo; Phone Number: 86459 5196612111; Email: abbie.pardo@lhsc.on.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. . Patients with permanent AF/persistent AF (in AF)
2. . Patients with NYHA Class II -IVa HF symptoms
3. . NT-proBNP ≥ 900 ng/L, or ≥ 600 ng/L if the patient has had a HF hospitalization within 1 year despite of guideline-driven medical therapy for HF of at least 3 months
4. . any QRS duration for patients with LVEF >35%, QRS duration <150 ms for patients with LVEF ≤35%

Exclusion Criteria:

1. In hospital patients needing intensive care or intravenous inotropic agent in the last 4 days
2. patients with a life expectancy of ≤ 1 year from non-cardiac cause or anticipating a transplant within 1year
3. acute coronary syndrome <4 weeks or coronary revascularization <3months
4. unable or unwilling to provide informed consent
5. uncorrected primary valvular disease or prosthetic tricuspid valve
6. restrictive, hypertrophic, or reversible form of cardiomyopathy
7. severe pulmonary diseases such as cor pulmonale or pulmonary hypertension (≥35mmHg)
8. patients enrolled in competitive clinical trials that will affect the objectives of this study;
9. existing CRT/BiVP or pacemaker
10. resting heart rate ≥110 bpm on Holter monitoring
11. patients who are pregnant or intend to become pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pharmacological Therapy; Patients randomized to pharmacology rate control will receive guideline-directed HF management across all ranges of LVEF, including appropriate rate control medications. ICD will be inserted in those patients who have LVEF ≤35%	Drug: Medication; Optimization of heart failure therapies includes maximum tolerated doses of beta-blockers, aldosterone antagonists, ACE inhibitors, ARB, diuretics, ARNis; Other Names: Optimal heart failure therapy
Experimental: P&A-BiVP; Patients randomized to P&A-BiVP will receive a cardiac resynchronization therapy (CRT) pulse generator, and ICD if LVEF ≤35% within 10 working days of randomization. Catheter AVNA will be performed within 4 weeks.	Device: Pace and Ablate; BiVentricular Pacing (BiVP) or Conduction System Pacing(CSP) followed by AtrioVentricular Node Ablation (AVNA); Other Names: P&A, pacemaker and atrioventricular node ablation
Experimental: P&A-CSP; Patients randomized to P&A-CSP will receive a CSP and ICD if LVEF ≤35% within 10 working days of randomization. Catheter AVNA will be performed within 4 weeks.	Device: Pace and Ablate; BiVentricular Pacing (BiVP) or Conduction System Pacing(CSP) followed by AtrioVentricular Node Ablation (AVNA); Other Names: P&A, pacemaker and atrioventricular node ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Winratio	Reduction in the hierarchical composite outcomes of all-cause mortality and HF events frequency, and improvement in QOL.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Mortality from any cause within the 12 month of follow up period	12 months
Cardiovascular mortality	Mortality attributed to cardiovascular causes within 12 month follow up period	12 months
Number of heart failure events	Heart failure related presentations to health care facilities necessitating intravenous diuretics or overnight stay	12 months
All-cause hospitalization	ER admission or overnight stay	12 months
Quality of Life -Kansas City Cardiomyopathy Questionairre (KCCQ)	Change in Kansas HF score from baseline. KCCQ is a 23-item self-administered questionnaire that measures the participant's perception of their health status, including their HF symptoms, impact on physical and social function and how their HF impacts the quality of life (QoL). KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), QoL (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.	6 months
Exercise	change in 6 minute walk distance from baseline	6 months
Biochemical marker	Change in NTproBNP from baseline	6 months

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Failure; Atrial Fibrillation
• Other Study ID Numbers: 4754

Drug and device information, study documents

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