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

Heart Failure Clinical Trial

— RHYTHM  

Official title:

A Multicenter, Interventional, Open-label and Single-arm Study to Investigate the Effect of ARNI on Ventricular Arrhythmia in HFrEF Patients With ICD or CRT-D

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04491136
• Other study ID #: CLCZ696BCN04
• Status: Terminated
• Phase: Phase 4
• Start date: November 11, 2020
• Est. completion date: June 8, 2023

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to generate effectiveness data of ARNI, in the Chinese HFrEF patients with implanted ICD or CRT-D. This will be a multicenter, interventional, open-label, and prospective single-arm study to evaluate the effect of ARNI on VAs in approximately 219 HFrEF patients receiving ICD or CRT-D in China.

Description:

The rationale of this study is to compare the effect of ACEI/ARB with the effect of ARNI on VA events for HFrEF patients with ICD or CRT-D, thus a multicenter, interventional, open-label, and prospective single-arm study was considered.

Study design:This will be a multicenter, interventional, open-label, and prospective single-arm study to evaluate the effect of ARNI on VAs in approximately 219 HFrEF patients receiving ICD or CRT-D in China.

After the patient is informed and asked to sign an informed consent form, baseline data will be collected. Device data of patients will be collected for 12 months. ACEI/ARB will be given to the patient for 6 months. Dosage of ACEI/ARB will be based on investigator's discretion and up titrated after 2-4 weeks to the maximum dosage the patients can tolerate and according to product label.After 6 months, patients using ACEI need to undergo a 36-hr washout period (36-hr washout period is not needed for patients using ARB at month 6). Patients will then receive ARNI (sponsored by Novartis only for this study) while the dosage of ARNI will be according to investigator's discretion and up titrated to the maximum dosage the patient can tolerate or 200 mg bid as per guideline.All patients will be followed up for 6 months for each treatment. After patients finalize the trial, the investigator will evaluate all patients and produce a report.

Primary objective of this study is to assess the proportion of patients with VA events over 6 months of ACEI/ARB and 6 months of ARNI treatment.

Secondary Objectives include:To assess numbers of occurrences of VA events and ICD or CRT-D shocks over 6 months of ACEI/ARB and 6 months of ARNI treatment; To compare the changes in LVEF and NYHA level between ACEI/ARB and ARNI treatment; To compare the changes in the NT-proBNP level between ACEI/ARB and ARNI treatments; To compare the healthcare resource utilization of HF patients during ACEI/ARB and ARNI treatments;

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 201
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Other protocol- defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Heart Failure

Intervention

Drug:
• ACEI/ARB
initative ACE/ARB drug for 6 months in this study
• ARNI
initative ARNI drug for next 6 months in this study

Locations

Country	Name	City	State
China	Novartis Investigative Site	Bei Jing	Bei Jing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Dalian	Liaoning
China	Novartis Investigative Site	Fuzhou	Fujian
China	Novartis Investigative Site	Guangzhou
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hefei	An Hui
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nantong	Jiangsu
China	Novartis Investigative Site	Qingdao	Shandong
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shenzhen	Guangdong
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wu XI	Jiangsu
China	Novartis Investigative Site	Wulumuqi	Xinjiang
China	Novartis Investigative Site	Xian	Shanxi
China	Novartis Investigative Site	Xuzhou	Jiangsu
China	Novartis Investigative Site	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with VA, ICD and ATP events over 6 months of ACEI/ARB and 6 months of ARNI treatment	Paired proportion of patients by occurrence of at least one Ventricular arrhythmia (VA), Implantable cardioverter defibrillator (ICD ) & Antitachycardia pacing (ATP) event over 6 months of Angiotensin-converting enzyme inhibitor/Angiotensin receptor blockers(ACEI/ARB) & Angiotensin receptor neprilysin inhibitor (ARNI) treatment respectively. VA events defined as: NSVT(Non-sustained ventricular tachycardia), SVT(Sustained ventricular tachycardia),PVC(Premature ventricular contraction), SVT is defined as: tachycardia with haemodynamic disorder or lasting for =30 seconds. NSVT is defined as: different ICD devices. PVC is defined as: early ventricular depolarization as determined by device.; ICD events: Ventricular tachycardia occurrence in implantable cardioverter defibrillator (ICD) patients may result in shock delivery & is associated with increased morbidity & mortality.; ATP events: Anti-tachycardia pacing is defined as a low-energy alternative to high-energy biphasic shocks.	Up to 12 months
Secondary	Numbers of NSVT, SVT, PVC, ICD shock and ATP 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	baseline, 6 month, 12 month
Secondary	LVEF (%)	To compare the changes in Left Ventricular Ejection Fraction (LVEF) between ACEI/ARB and ARNI treatments	baseline, 6 month, 12 month
Secondary	NYHA level	To compare the changes in New York Heart Association (NYHA) level between ACEI/ARB and ARNI treatments	baseline, 6 month, 12 month
Secondary	NT-proBNP (pg/mL) level	To compare the changes in the N-Terminal prohormone of Brain Natriuretic Peptide(NT-proBNP) level between ACEI/ARB and ARNI treatments	baseline, 6 month, 12 month
Secondary	Number of hospitalizations for arrhythmia or HF related hospitalizations	To compare the healthcare resource utilization of Heart Failure (HF) patients during ACEI/ARB and ARNI treatments	baseline, 6 month, 12 month