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

Phase 4TerminatedNCT04491136

Novartis Pharmaceuticals201 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

201

Conditions

Heart Failure

Interventions

ACEI/ARBDRUG

Oral ACE/ARB drug according to the investigator's discretion for the first 6 months in this study

ARNIDRUG

Oral sacubitril/valsartan at the dosage of investigators discretion, whit a target dose of 200mg bid for the next 6 months of this study

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Key Inclusion criteria: 1. Male or female patients ≥18 and ≤80 years of age 2. Implanted with an ICD or CRT-D within 2 weeks 3. NYHA functional class II - IV 4. LVEF ≤40% (measured by echocardiography) 5. Signed informed consent must be obtained prior to participation in the study. Key Exclusion criteria 1. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes. 2. Patient received target dose (≥200 mg/d) of ARNI for 2 weeks continuously within the 6-week period prior to study enrollment. 3. Participation in other clinical studies 3 months prior to participating study. 4. Advanced cancer or other significant comorbidities with life expectancy of \<1 year. 5. Previous history of angioedema associated with ACEI/ARB treatment, hereditary or idiopathic angioedema. 6. Patients with renal artery stenosis history. 7. Current stage D HF patients requiring vasoactive drugs. 8. Symptomatic hypotension \< 100/60 mmHg at visit 1 (screening) or Symptomatic hypotension \< 90/60 mmHg in anti-hypertension drug treatment at visit 1 (screening). 9. Serum potassium \>5.4 mmol/L at visit 1 (screening). 10. Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 as measured at visit 1 (screening). 11. Pregnant or nursing (lactating) women. 12. Other exclusion depend on investigator's discretion.

Locations (23)

Novartis Investigative Site

Hefei, Anhui, China

Outcomes

Primary Outcomes

Proportion of Paired Patients With Ventricular Arrhythmia (VA) Events

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

Time frame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)

Proportion of Paired Patients Who Experienced at Least One ICD or CRT-D Shock and ATP Event

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.

Time frame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)

Secondary Outcomes

Pairwise Number of SVT, NSVT, PVC, ICD or CRT-D Shocks and ATP Events Experienced by Patients

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

Time frame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)

Left Ventricular Ejection Fraction

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.

Data from ClinicalTrials.gov

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