Program of Angiotensin-Neprilysin Inhibition in Admitted Patients With Worsening Heart Failure (PREMIER)

Saga University

Status and phase: Active, not recruiting; Phase 4

Conditions: Heart Failure

Treatments: Drug: Sacubitril Valsartan Sodium Hydrate; Drug: Standard treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT05164653

00001

Details and patient eligibility

About

The aim of this study is to assess the treatment effect of sacubitril valsartan versus conventional therapy for heart failure (HF) in admitted patients due to exacerbation of HF on the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) concentrations.

Full description

The high rate of rehospitalization and mortality of patients hospitalized for acute exacerbation of HF, especially at the early phase after discharge, has long been a serious clinical concern. However, few trials evaluating drug therapies on the post-acute phase of HF showed positive and/or satisfying results. Therefore, it is urgently required to establish an efficient treatment strategy at that phase. Sacubitril valsartan is an angiotensin receptor-neprilysin inhibitor that was approved in Japan in 2020 for patients who are taking standard care of HF.

In this investigator-initiated, multicenter, 8-week, randomized controlled study (PREMIER), the investigators try to assess the effect of in-hospital initiation of sacubitril valsartan, compared to standard HF treatment, in patients who were admitted due to worsening heart failure, on the NT-proBNP concentrations.

Enrollment: 400 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients must provide written informed consent themselves to participate in this study
2. Aged 20 or older at consent (male or female)
3. Hospitalized due to worsening heart failure with both signs of congestion (such as edema, moist rales, and congestion on chest X-ray) and symptoms of heart failure (such as dyspnea on mild exertion or at rest) (any level of left ventricular ejection fraction)
4. NYHA class II-IV
5. Taking an ACE inhibitor or an ARB
6. Can undergo randomization within 7 days of current hospitalization
7. Patients who meet the following criteria of hemodynamic stability I. Systolic blood pressure ≥100 mm Hg II. No dose increase of intravenous diuretic within 6 hours before randomization III. No intravenous administration of vasodilator (such as carperitide or nitrates) or positive inotropic agent
8. Patients who meet the following reference range for natriuretic peptide level from 48 hours before current hospitalization to the time of eligibility determination

NT-proBNP ≥1200 pg/mL or BNP ≥300 pg/mL

Exclusion criteria

1. Currently taking oral sacubitril valsartan or have taken it within 30 days prior to randomization
2. History of hypersensitivity to ingredients in ARB, ACE inhibitor, or sacubitril valsartan; or expected to be contraindicated for or intolerant to any of these drugs
3. History of angioedema
4. Severe renal dysfunction (<eGFR 30 mL/min/1.73 m^2), on maintenance dialysis, or known bilateral renal artery stenosis (in patients with solitary kidney, known renal artery stenosis in the residual kidney)
5. Severe liver dysfunction (Child-Pugh class C)
6. Diabetic patients who are currently taking aliskiren fumarate
7. Serum potassium ≥5.3 mEq/L or more
8. Cardiogenic shock
9. On cardiopulmonary support, with a left ventricular assist device, or on a ventilator
10. Onset of stroke or acute coronary syndrome within 30 days prior to randomization
11. History of surgical or percutaneous treatment of cardiovascular disease within 30 days prior to randomization
12. Patients with an advanced plan for surgical or percutaneous treatment of cardiovascular disease or for coronary artery revascularization during an observation period
13. Patients with an advanced plan for pacemaker implantation, cardiac resynchronization therapy, or electrical cardioversion during an observation period
14. History or comorbidity of hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy such as amyloidosis or sarcoidosis
15. Active pericardial disease
16. History of or awaiting heart transplant
17. Severe chronic respiratory disease or active infectious disease
18. Patients who are or might become pregnant or who are breastfeeding
19. Patients whom a study investigator determined to be unsuitable for the study (such as patients with comorbid active malignancy)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Sacubitril Valsartan Sodium Hydrate

Experimental group

Description:

Entresto® Tablets

Treatment:

Drug: Sacubitril Valsartan Sodium Hydrate

No Sacubitril Valsartan Sodium Hydrate

Active Comparator group

Description:

Standard treatment for HF (ARB, ACE inhibitor etc.)

Treatment:

Drug: Standard treatment