Effect of Angiotensin-Neprilysin Inhibition (ARNI) on Prognosis of Chronic Heart Failure

Study Overview
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Brief Summary
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This study is a randomized controlled multicenter clinical trial, in which about 340 patients with newly diagnosed or prior diagnosed chronic heart will be recruited. Patients will be randomly divided into Angiotensin-Neprilysin Inhibition (ARNI) group and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) group. All-cause death, cardiac death and re-hospitalization due to heart failure will be evaluated in 1, 3, 6, 12 months after recruitment.

Detailed Description
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Chronic heart failure is associated with poor prognosis in cardiac patients, although systemic effective drugs has been applied in these patients. European Society of Cardiology (ESC) has recommended ARNI Sacubitril/Valsartan as first-line drugs in replacement of ACEI (I, B) in 2016 for these patients. While American College of Cardiology and The American Heart Association (ACC/AHA) made a first-line recommendation that patients with heart failure due to reduced ejection fraction (HFrEF) could be administrated ARNI directly. Hence, we apply this trial to find if ARNI could replace ACEI/ARB to provide insights for better treatment of chronic heart failure in China. This study is a randomized controlled multicenter clinical trial, in which about 340 patients with newly diagnosed or prior diagnosed chronic heart will be recruited. Patients will be randomly divided into Angiotensin-Neprilysin Inhibition (ARNI) group and ACEI/ARB group. All-cause death, cardiac death and re-hospitalization due to heart failure will be evaluated in 1, 3, 6, 12 months after recruitment. Other safety assessment including left ventricular ejection fraction (LVEF), 6 minutes walk test will be followed up as well.

Official Title
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A Multicenter, Randomized Controlled Trial of Angiotensin-Neprilysin Inhibition (ARNI) in the Chronic Heart Failure

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Drug: Entresto
* Drug: ACEI/ARB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 HFrEF, defined as LVEF≤40% and New York Heart Association (NYHA) class ≥ II. Plasma NT-proBNP ≥ 600 pg/ml, or NT-proBNP ≥ 400 pg/ml if patients have been hospitalized for heart failure in 12 months. If patients have been taking ACEI/ARB at recruitment, a stable dose equivalent to at least 10mg/day of enalapril will be required. Volunteer for the study and sign the informed consent. Exclusion Criteria: Symptomatic hypotension, systolic blood pressure < 95 mmHg at baseline. eGFR < 30 ml(/min*1.73m2) at baseline. Serum potassium > 5.4 mmol/L at baseline. Contraindication of ACEI or ARB.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Newly diagnosed HFrEF ARNI<br>Newly diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study. | Drug: Entresto<br>* Sacubitril Valsartan Sodium Tablets, 100mg bid, among whole study<br>|
| Active Comparator: Newly diagnosed HFrEF ACEI/ARB<br>Newly diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study. | Drug: ACEI/ARB<br>* Choose one of ACEI/ARB according to the clinical condition among the whole study.<br>|
| Experimental: Prior diagnosed HFrEF ARNI<br>Prior diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study. | Drug: Entresto<br>* Sacubitril Valsartan Sodium Tablets, 100mg bid, among whole study<br>|
| Active Comparator: Prior diagnosed HFrEF ACEI/ARB<br>Prior diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study. | Drug: ACEI/ARB<br>* Choose one of ACEI/ARB according to the clinical condition among the whole study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular events | Composite outcomes of all-cause death including cardiac death and re-hospitalization due to heart failure | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-minutes walking test | A test evaluating cardiac function. | Test in 1, 3, 6, 12 months comparing to the baseline. | 
| LVEF | Left ventricular ejection fraction. | Test in 1, 3, 6, 12 months comparing to the baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACEI/ARB, Shakurba valsartan, Heart failure