Clinical trial NCT04491136: Effective Study of ARNI on Ventricular Arrhythmia in HFrEF Patients With ICD or CRT-D (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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Heart Failure
Keywords: LCZ696
sacubitril/valsartan
Heart Failure
Heart failure with reduced ejection fraction
HFrEF
Ventricular arrhythmias
Implanted Device
Healthcare resource utilization
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-07-29
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Paired Patients With Ventricular Arrhythmia (VA) Events
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
measure: Proportion of Paired Patients Who Experienced at Least One ICD or CRT-D Shock and ATP Event
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
Secondary outcomes:
measure: Pairwise Number of SVT, NSVT, PVC, ICD or CRT-D Shocks and ATP Events Experienced by Patients
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
measure: Left Ventricular Ejection Fraction
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
measure: New York Heart Association Classification
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
measure: N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Level
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
measure: Number of Hospitalizations for Arrhythmia or HF Related Hospitalizations
timeFrame: Up to 12 months (6 months of ACEI/ARB treatment and 6 months of ARNI treatment)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Novartis Investigative Site
state: An Hui
city: Bei Jing
country: China
facility: Novartis Investigative Site
state: Bei Jing
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Fuzhou
country: China
facility: Novartis Investigative Site
state: Fujian
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shenzhen
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Zhengzhou
country: China
facility: Novartis Investigative Site
state: Henan
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nantong
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Wu XI
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Xuzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Dalian
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Wulumuqi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Qingdao
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: