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

NCT04491136 | Terminated Phase 4 Results

• 1 other identifier: CLCZ696BCN04
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 23

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).

Conditions

Heart Failure

Keywords

LCZ696; sacubitril/valsartan; Heart Failure; Heart failure with reduced ejection fraction; HFrEF; Ventricular arrhythmias; Implanted Device; Healthcare resource utilization

Outcome Measures

Primary Outcomes (2)

• 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

  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.

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

Secondary Outcomes (5)

• 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)

• Left Ventricular Ejection Fraction

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

• New York Heart Association Classification

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

• 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)

• 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)

Study Arms (1)

ACEI/ARB treatment for 6 months/ARNI treatment the next 6 months

EXPERIMENTAL

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.

Drug: ACEI/ARB; Drug: ARNI

Interventions

ACEI/ARB DRUG

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

ACEI/ARB treatment for 6 months/ARNI treatment the next 6 months

ARNI DRUG

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

Also known as: Entresto

ACEI/ARB treatment for 6 months/ARNI treatment the next 6 months

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 and ≤80 years of age
• Implanted with an ICD or CRT-D within 2 weeks
• NYHA functional class II - IV
• LVEF ≤40% (measured by echocardiography)
• Signed informed consent must be obtained prior to participation in the study.

You may not qualify if:

• History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
• Patient received target dose (≥200 mg/d) of ARNI for 2 weeks continuously within the 6-week period prior to study enrollment.
• Participation in other clinical studies 3 months prior to participating study.
• Advanced cancer or other significant comorbidities with life expectancy of \<1 year.
• Previous history of angioedema associated with ACEI/ARB treatment, hereditary or idiopathic angioedema.
• Patients with renal artery stenosis history.
• Current stage D HF patients requiring vasoactive drugs.
• Symptomatic hypotension \< 100/60 mmHg at visit 1 (screening) or Symptomatic hypotension \< 90/60 mmHg in anti-hypertension drug treatment at visit 1 (screening).
• Serum potassium \>5.4 mmol/L at visit 1 (screening).
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 as measured at visit 1 (screening).
• Pregnant or nursing (lactating) women.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Novartis Investigative Site

Hefei, Anhui, 230001, China

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100034, China

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100044, China

Location

Novartis Investigative Site

Fuzhou, Fujian, 350001, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Shenzhen, Guangdong, 518057, China

Location

Novartis Investigative Site

Zhengzhou, Henan, 450000, China

Location

Novartis Investigative Site

Changsha, Hunan, 410011, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210000, China

Location

Novartis Investigative Site

Nantong, Jiangsu, 226000, China

Location

Novartis Investigative Site

Wuxi, Jiangsu, 214023, China

Location

Novartis Investigative Site

Xuzhou, Jiangsu, 221000, China

Location

Novartis Investigative Site

Dalian, Liaoning, 116011, China

Location

Novartis Investigative Site

Shenyang, Liaoning, 110011, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200032, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200433, China

Location

Novartis Investigative Site

Xian, Shanxi, 710061, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610031, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Ürümqi, Xinjiang, 830054, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310014, China

Location

Novartis Investigative Site

Qingdao, 266000, China

Location

Novartis Investigative Site

Tianjin, 300000, China

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: July 29, 2020
• Study Start: November 11, 2020
• Primary Completion: June 8, 2023
• Study Completion: June 8, 2023
• Last Updated: May 16, 2025
• Results First Posted: October 17, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (23)