Effective Study of ARNI on Ventricular Arrhythmia in HFrEF Patients With ICD or CRT-D (RHYTHM)

Phase 4

Terminated

• Conditions: Heart Failure
• Interventions: Drug: ACEI/ARB; Drug: ARNI

• Registration Number: NCT04491136
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this study was to generate effectiveness data of Angiotensin receptor neprilysin inhibitor (ARNI), in the Chinese Heart failure with reduced ejection fraction (HFrEF) patients with implantable cardioverted defibrillator (ICD) or Cardiac resynchronization therapy-defibrillator (CRT-D).

Detailed Description

The rationale of this study was to compare the effect of angiotensin-converting enzyme inhibitor (ACEI) / Angiotensin receptor blockers (ARB) with the effect of ARNI on ventricular arrhythmia (VA) events for HFrEF patients with ICD or CRT-D, thus a multicenter, interventional, open-label, and prospective single-arm study was considered.

ACEI/ARB was given to the patient for 6 months. After 6 months, patients using ACEI needed to undergo a 36-hr washout period (36-hr washout period was not needed for patients using ARB at month 6). Patients then received ARNI (sponsored by Novartis only for this study).

Study Timeline

• Study First Submitted: 2020-06-22
• Study First Submitted QC: 2020-07-28
• Study First Posted: 2020-07-29
• Study Start: 2020-11-11
• Primary Completion: 2023-06-08
• Study Completion: 2023-06-08
• Results First Submitted: 2024-06-03
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-14
• Last Update Submitted: 2024-10-14
• Results First Posted: 2024-10-17
• Last Update Posted: 2024-10-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 201

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACEI/ARB treatment for 6 months/ARNI treatment the next 6 months	ACEI/ARB	Patients received angiotensin-converting enzyme inhibitor/angiotensin receptor blockers treatment the first 6 months. The following 6 months patients received angiotensin receptor neprilysin inhibitor treatment.
ACEI/ARB treatment for 6 months/ARNI treatment the next 6 months	ARNI	Patients received angiotensin-converting enzyme inhibitor/angiotensin receptor blockers treatment the first 6 months. The following 6 months patients received angiotensin receptor neprilysin inhibitor treatment.

Primary Outcome Measures

Name	Time	Method
Proportion of Paired Patients With Ventricular Arrhythmia (VA) Events	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	VA events were measured through devices to determine sustained ventricular tachycardia (SVT), non-sustained ventricular tachycardia (NSVT) and premature ventricular contraction (PVC).; SVT was defined as tachycardia lasting for ≥30 seconds or with hemodynamic disorder as determined by Holter and/or device.; NSVT was defined as recorded by Holter and/or device. PVC was defined as an early ventricular depolarization as determined by the device, and/or detected by Holter.; PVC data were not available for patients with single -lumen implantation type
Proportion of Paired Patients Who Experienced at Least One ICD or CRT-D Shock and ATP Event	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	Once VA events were detected, implantable cardioverter defibrillator (ICD) could treat with high-energy shocks or Anti-tachycardia pacing (ATP). ATP consists of one or more trains of pacing stimuli, expressed as a percentage of the tachycardia cycle length for a given RR interval, from the onset of the preceding R wave.; Patients with sustained VA events would receive ICD or cardiac resynchronization therapy-defibrillator (CRT-D) shock therapy.

Secondary Outcome Measures

Name	Time	Method
Pairwise Number of SVT, NSVT, PVC, ICD or CRT-D Shocks and ATP Events Experienced by Patients	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	To assess the number of occurrences of Ventricular arrhythmia (VA) events and Implantable cardioverter defibrillator (ICD) or Cardiac resynchronization therapy-defibrillator (CRT-D) shocks over 6 months of ACEI/ARB and 6 months of ARNI treatment.; PVC data were not available for patients with single-lumen implantation type
Left Ventricular Ejection Fraction	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	To compare the changes in Left Ventricular Ejection Fraction (LVEF) between ACEI/ARB and ARNI treatments.; LVEF is a measurement expressed as a percentage of how much blood in the left ventricle is pumped out with each contraction of the heart.
New York Heart Association Classification	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	To compare the changes in New York Heart Association (NYHA) level between ACEI/ARB and ARNI treatments.; NYHA classification is a subjective physician's assessment of heart failure patient's functional capacity and symptomatic status.; Class I - No limitation of physical activity. Class II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). Class III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV - Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Level	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	To compare the changes in the N-Terminal prohormone of Brain Natriuretic Peptide(NT-proBNP) level between ACEI/ARB and ARNI treatments.; NT-proBNP are small proteins produced in large amounts when the heart senses it needs to work harder, such as in heart failure.
Number of Hospitalizations for Arrhythmia or HF Related Hospitalizations	Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)	To compare the healthcare resource utilization of Heart Failure (HF) patients during ACEI/ARB and ARNI treatments

Trial Locations

Locations (1)

Novartis Investigative Site; 🇨🇳 Tianjin, China