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

NCT05164653 | Active Not Recruiting Phase 4

• 1 other identifier: 00001
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure

Keywords

Acute decompensated heart failure; Heart failure hospitalization; Sacubitril valsartan; NT-proBNP

Outcome Measures

Primary Outcomes (1)

• Proportional change in NT-proBNP concentrations from baseline to 8 weeks

  Group ratio of the proportional change in the geometric mean of NT-proBNP concentrations from baseline to 8 weeks after protocol treatment initiation

  8 weeks

Secondary Outcomes (108)

• Proportional change in NT-proBNP concentrations from baseline to 4 weeks

  4 weeks

• Reduction in NT-proBNP levels at 8 weeks

  8 weeks

• Reduction in NT-proBNP levels at 4 weeks

  4 weeks

• Mean reduction in NT-proBNP at 4 and 8 weeks

  4 weeks, 8 weeks

• Amount of change in biomarkers (cardiac troponin T)

  8 weeks

Study Arms (2)

Sacubitril Valsartan Sodium Hydrate

EXPERIMENTAL

Entresto® Tablets

Drug: Sacubitril Valsartan Sodium Hydrate

No Sacubitril Valsartan Sodium Hydrate

ACTIVE COMPARATOR

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

Drug: Standard treatment

Interventions

Sacubitril Valsartan Sodium Hydrate DRUG

Switch from the ACE inhibitor or ARB that was taken before the allocation, and start oral administration twice daily with a starting dose of 50 mg of sacubitril valsartan. The duration of administration of the ACE inhibitor or ARB before allocation does not matter, but when switching from the ACE inhibitor, administration of sacubitril valsartan should be started at least 36 hours after the final administration of the drug. After the start of administration, the dose is gradually increased to 100 mg and 200 mg once at intervals of 2 to 4 weeks, referring to the latest package insert and safety and tolerability standards. At that time, if the doctor in charge determines that the dose is not tolerated after the dose is increased, the dose may be reduced to the previous dose or the drug may be suspended depending on the medical situation.

Also known as: Entresto® Tablets, Novartis Pharma K.K.

Sacubitril Valsartan Sodium Hydrate

Standard treatment DRUG

Standard treatment, other than Sacubitril Valsartan Sodium Hydrate, for HF

Also known as: Angiotensin Converting Enzyme(ACE) inhibitor or Angiotensin II Receptor Blocker(ARB) etc.

No Sacubitril Valsartan Sodium Hydrate

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must provide written informed consent themselves to participate in this study
• Aged 20 or older at consent (male or female)
• 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)
• NYHA class II-IV
• Taking an ACE inhibitor or an ARB
• Can undergo randomization within 7 days of current hospitalization
• 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
• 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

You may not qualify if:

• Currently taking oral sacubitril valsartan or have taken it within 30 days prior to randomization
• 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
• History of angioedema
• 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)
• Severe liver dysfunction (Child-Pugh class C)
• Diabetic patients who are currently taking aliskiren fumarate
• Serum potassium ≥5.3 mEq/L or more
• Cardiogenic shock
• On cardiopulmonary support, with a left ventricular assist device, or on a ventilator
• Onset of stroke or acute coronary syndrome within 30 days prior to randomization
• History of surgical or percutaneous treatment of cardiovascular disease within 30 days prior to randomization
• Patients with an advanced plan for surgical or percutaneous treatment of cardiovascular disease or for coronary artery revascularization during an observation period
• Patients with an advanced plan for pacemaker implantation, cardiac resynchronization therapy, or electrical cardioversion during an observation period
• History or comorbidity of hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy such as amyloidosis or sarcoidosis
• Active pericardial disease

Sponsors & Collaborators

• Saga University: lead

Study Sites (1)

Saga University Hospital

Saga, 849-8501, Japan

Location

Related Publications (1)

• Tanaka A, Kida K, Matsue Y, Imai T, Suwa S, Taguchi I, Hisauchi I, Teragawa H, Yazaki Y, Moroi M, Ohashi K, Nagatomo D, Kubota T, Ijichi T, Ikari Y, Yonezu K, Takahashi N, Toyoda S, Toshida T, Suzuki H, Minamino T, Nogi K, Shiina K, Horiuchi Y, Tanabe K, Hachinohe D, Kiuchi S, Kusunose K, Shimabukuro M, Node K. In-hospital initiation of angiotensin receptor-neprilysin inhibition in acute heart failure: the PREMIER trial. Eur Heart J. 2024 Nov 8;45(42):4482-4493. doi: 10.1093/eurheartj/ehae561.

  PMID: 39215531 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Koichi Node, Pr.,Dr.

  Saga University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 21, 2021
• Study Start: December 27, 2021
• Primary Completion: February 8, 2024
• Study Completion: March 1, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

JP (1)