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

NCT ID: NCT05164653

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-27
• Study Completion Date: 2025-03-31

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.

Detailed 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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sacubitril Valsartan Sodium Hydrate

Entresto® Tablets

Group Type: EXPERIMENTAL

Sacubitril Valsartan Sodium Hydrate

Intervention Type: 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.

No Sacubitril Valsartan Sodium Hydrate

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

Group Type: ACTIVE_COMPARATOR

Standard treatment

Intervention Type: DRUG

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

Interventions

Sacubitril Valsartan Sodium Hydrate

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.

Intervention Type: DRUG

Standard treatment

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

Intervention Type: DRUG

Other Intervention Names

Entresto® Tablets, Novartis Pharma K.K.; Angiotensin Converting Enzyme(ACE) inhibitor or Angiotensin II Receptor Blocker(ARB) etc.

Eligibility Criteria

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)

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saga University

OTHER

Sponsor Role: lead

Responsible Party

Koichi Node

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Koichi Node, Pr.,Dr.

Role: PRINCIPAL_INVESTIGATOR

Saga University Hospital

Locations

Saga University Hospital

Saga, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 39215531 (View on PubMed)

Other Identifiers

00001

Identifier Type: -

Identifier Source: org_study_id