Heart FailurePhase 4NCT05164653
Program of Angiotensin-Neprilysin Inhibition in Admitted Patients With Worsening Heart Failure (PREMIER)
A Phase 4 study testing Sacubitril Valsartan Sodium Hydrate and Standard treatment in people with Heart Failure, run by Saga University at 1 site in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sacubitril Valsartan Sodium Hydrate and Standard treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteJapan
- Study dates
- 27 Dec 2021to Mar 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
- History of or awaiting heart transplant
- Severe chronic respiratory disease or active infectious disease
- Patients who are or might become pregnant or who are breastfeeding
- Patients whom a study investigator determined to be unsuitable for the study (such as patients with comorbid active malignancy)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Investigator-initiated, Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint Study to Assess the Effect of In-hospital Initiation of Sacubitril Valsartan on the NT-proBNP Concentrations in Patients Admitted Due to Acute Exacerbation of Heart Failure (PREMIER)
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.
Read the 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
- Being tested
- Sacubitril Valsartan Sodium Hydrate, Standard treatment
- Keywords
- Acute decompensated heart failure, Heart failure hospitalization, Sacubitril valsartan, NT-proBNP
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril Valsartan Sodium HydrateDrug
Also called Entresto® Tablets, Novartis Pharma K.K.
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 called Angiotensin Converting Enzyme(ACE) inhibitor or Angiotensin II Receptor Blocker(ARB) etc.
Standard treatment, other than Sacubitril Valsartan Sodium Hydrate, for HF
| Study group | Role | What they receive |
|---|---|---|
| Sacubitril Valsartan Sodium Hydrate | Experimental | Entresto® Tablets Receives: Drug: Sacubitril Valsartan Sodium Hydrate |
| No Sacubitril Valsartan Sodium Hydrate | Active comparator | Standard treatment for HF (ARB, ACE inhibitor etc.) Receives: Drug: Standard treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 8 weeks
Secondary outcomes (108)
Proportional change in NT-proBNP concentrations from baseline to 4 weeks
Group ratio of the proportional change in the geometric mean of NT-proBNP concentrations from baseline to 4 weeks after protocol treatment initiation
Measured: 4 weeks
Reduction in NT-proBNP levels at 8 weeks
Percentage of patients with at least a 50% reduction in NT-proBNP levels at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Reduction in NT-proBNP levels at 4 weeks
Percentage of patients with at least a 30% reduction in NT-proBNP levels at 4 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks
Mean reduction in NT-proBNP at 4 and 8 weeks
Percentage of patients with at least a 40% reduction from baseline in mean NT-proBNP at 4 and 8 weeks after protocol treatment initiation
Measured: 4 weeks, 8 weeks
Amount of change in biomarkers (cardiac troponin T)
Amount of change in cardiac troponin T at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in biomarkers (cardiac troponin T)
Percent change in cardiac troponin T at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in biomarkers (C-reactive protein)
Amount of change in C-reactive protein at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in biomarkers (C-reactive protein)
Percent change in C-reactive protein at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in biomarkers (growth differentiation factor 15)
Amount of change in growth differentiation factor 15 at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in biomarkers (growth differentiation factor 15)
Percent change in growth differentiation factor 15 at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in biomarkers (soluble suppression of tumorigenesis-2)
Amount of change in soluble suppression of tumorigenesis-2 at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in biomarkers (soluble suppression of tumorigenesis-2)
Percent change in soluble suppression of tumorigenesis-2 at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in biomarkers (glycoalbumin)
Amount of change in glycoalbumin at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in biomarkers (glycoalbumin)
Percent change in glycoalbumin at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in biomarkers (1.5-anhydro-D-glucitol)
Amount of change in 1.5-anhydro-D-glucitol at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in biomarkers (1.5-anhydro-D-glucitol)
Percent change in 1.5-anhydro-D-glucitol at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in clinical parameters (weight)
Amount of change in weight at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (weight)
Percent change in weight at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (body mass index)
Amount of change in body mass index at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (body mass index)
Percent change in body mass index at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (blood pressure)
Amount of change in systolic blood pressure and diastolic blood pressure at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (blood pressure)
Percent change in systolic blood pressure and diastolic blood pressure at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (heart rate)
Amount of change in heart rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (heart rate)
Percent change in heart rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of changs in clinical parameters (red blood cell)
Amount of change in red blood cell at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (red blood cell)
Percent change in red blood cell at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (hemoglobin)
Amount of change in hemoglobin at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (hemoglobin)
Percent change in hemoglobin at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of chang in clinical parameters (hematocrit)
Amount of change in hematocrit at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (hematocrit)
Percent change in hematocrit at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (platelet)
Amount of change in platelet at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (platelet)
Percent change in platelet at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (hemoglobin A1c)
Amount of change in hemoglobin A1c at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (hemoglobin A1c)
Percent change in hemoglobin A1c at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (fasting glucose)
Amount of change in fasting glucose at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (fasting glucose)
Percent change in fasting glucose at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (total cholesterol)
Amount of change in total cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (total cholesterol)
Percent change in total cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (high-density lipoprotein cholesterol)
Amount of change in high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (high-density lipoprotein cholesterol)
Percent change in high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (non-high-density lipoprotein cholesterol)
Amount of change in non-high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (non-high-density lipoprotein cholesterol)
Percent change in non-high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (triglyceride)
Amount of change in triglyceride at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (triglyceride)
Percent change in triglyceride at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (aspartate aminotransferase)
Amount of change in aspartate aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (aspartate aminotransferase)
Percent change in aspartate aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (alanine aminotransferase)
Amount of change in alanine aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (alanine aminotransferase)
Percent change in alanine aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (γ-glutamyl transpeptidase)
Amount of change in γ-glutamyl transpeptidase at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (γ-glutamyl transpeptidase)
Percent change in γ-glutamyl transpeptidase at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (uric acid)
Amount of change in uric acid at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (uric acid)
Percent change in uric acid at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (creatinine)
Amount of change in creatinine at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (creatinine)
Percent change in creatinine at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (estimated glomerular filtration rate)
Amount of change in estimated glomerular filtration rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (estimated glomerular filtration rate)
Percent change in estimated glomerular filtration rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (sodium)
Amount of change in sodium at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (sodium)
Percent change in sodium at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (potassium)
Amount of change in potassium at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (potassium)
Percent change in potassium at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (Fibrosis-4)
Amount of change in Fibrosis-4 at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (Fibrosis-4)
Percent change in Fibrosis-4 at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (estimated plasma volume)
Amount of change in estimated plasma volume at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (estimated plasma volume)
Percent change in estimated plasma volume at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in clinical parameters (New York Heart Association class)
Amount of change in New York Heart Association class at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Percent change in clinical parameters (New York Heart Association class)
Percent change in New York Heart Association class at 4 and 8 weeks after protocol treatment initiation compared with baseline
Measured: 4 weeks, 8 weeks
Amount of change in echocardiographic parameters (left ventricular end-diastolic volume)
Amount of change in left ventricular end-diastolic volume at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left ventricular end-diastolic volume)
Percent change in left ventricular end-diastolic volume at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left ventricular end-systolic volume)
Amount of change in left ventricular end-systolic volume at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left ventricular end-systolic volume)
Percent change in left ventricular end-systolic volume at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left ventricular ejection fraction)
Amount of change in left ventricular ejection fraction at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left ventricular ejection fraction)
Percent change in left ventricular ejection fraction at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (septal e')
Amount of change in septal e' at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (septal e')
Percent change in septal e' at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (lateral e')
Amount of change in lateral e' at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (lateral e')
Percent change in lateral e' at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (flow velocity pattern through the mitral orifice (E))
Amount of change in flow velocity pattern through the mitral orifice (E) at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (flow velocity pattern through the mitral orifice (E))
Percent change in flow velocity pattern through the mitral orifice (E) at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (early mitral inflow velocity E and mitral annular early diastolic velocity e')
Amount of change in early mitral inflow velocity E and mitral annular early diastolic velocity e' at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (early mitral inflow velocity E and mitral annular early diastolic velocity e')
Percent change in early mitral inflow velocity E and mitral annular early diastolic velocity e' at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left ventricular mass index)
Amount of change in left ventricular mass index at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left ventricular mass index)
Percent change in left ventricular mass index at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left atrial volume index)
Amount of change in left atrial volume index at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left atrial volume index)
Percent change in left atrial volume index at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left ventricular outflow tract)
Amount of change in left ventricular outflow tract at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left ventricular outflow tract)
Percent change in left ventricular outflow tract at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left ventricular outflow tract velocity time integral)
Amount of change in left ventricular outflow tract velocity time integral at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left ventricular outflow tract velocity time integral)
Percent change in left ventricular outflow tract velocity time integral at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (tricuspid regurgitation velocity)
Amount of change in tricuspid regurgitation velocity at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (tricuspid regurgitation velocity)
Percent change in tricuspid regurgitation velocity at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters(inferior vena cava diameter)
Amount of change in inferior vena cava diameter at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters(inferior vena cava diameter)
Percent change in inferior vena cava diameter at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (global longitudinal strain)
Amount of change in global longitudinal strain at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (global longitudinal strain)
Percent change in global longitudinal strain at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in echocardiographic parameters (left atrial strain (2-chamber view and 4-chamber view))
Amount of change in left atrial strain (2-chamber view and 4-chamber view) at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percent change in echocardiographic parameters (left atrial strain (2-chamber view and 4-chamber view))
Percent change in left atrial strain (2-chamber view and 4-chamber view) at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Change in echocardiographic parameters (inferior vena cava diameter)
Percentage of patients with at least a 50% respiratory variation in inferior vena cava diameter at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Amount of change in Kansas City Cardiomyopathy Questionnaire-12 score
Amount of change in Kansas City Cardiomyopathy Questionnaire-12 score at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Percentage of patients in Kansas City Cardiomyopathy Questionnaire-12 score
Percentage of patients with at least a 5-point increase in Kansas City Cardiomyopathy Questionnaire-12 score at 8 weeks after protocol treatment initiation compared with baseline
Measured: 8 weeks
Time to first occurrences of the composite event of all-cause death or worsening heart failure event
Time to first occurrences of the composite event of all-cause death or worsening heart failure event, defined as i) unplanned rehospitalization, ii) initiation of intravenous treatment (vasodilator or positive inotropic agent) for heart failure (during hospitalization: excludes at rehospitalization), iii) urgent visit due to heart failure requiring intravenous treatment (vasodilator, positive inotropic agent, or diuretic), or iv) initiation of oral diuretic (loop diuretic, thiazide-type diuretic, or tolvaptan) or at least a 50% increase in its dose (outpatient)
Measured: 8 weeks
Occurrences of the composite event of all-cause death or worsening heart failure events (total number of occurrences)
Total number of occurrences of the composite event of all-cause death or worsening heart failure events (first and recurrence)
Measured: 8 weeks
Occurrences of the composite event of all-cause death or worsening heart failure events (incidence of occurrences)
Incidence of occurrences of the composite event of all-cause death or worsening heart failure events (first and recurrence)
Measured: 8 weeks
Occurrences of the individual components of composite events and cardiovascular death (total number of occurrences)
Total number of occurrences of individual components of the following events: first and recurrent worsening heart failure events (i, ii, iii, and iv), all-cause mortality, and cardiovascular death
Measured: 8 weeks
Occurrences of the individual components of composite events and cardiovascular death (incidence of occurrences)
Incidence of occurrences of individual components of the following events: first and recurrent worsening heart failure events (i, ii, iii, and iv), all-cause mortality, and cardiovascular death
Measured: 8 weeks
Occurrences of the individual components of composite events and cardiovascular death (time until occurrence)
Time until occurrence of individual components of the following events: first and recurrent worsening heart failure events (i, ii, iii, and iv), all-cause mortality, and cardiovascular death
Measured: 8 weeks
Occurrences of adverse events of interest (total number of occurrences)
Total number of occurrences of specific adverse events, including decreased renal function (at least a 50% increase in serum creatinine or at least a 30% decrease in eGFR), hyperkalemia (serum potassium: 5.5 mEq/L or more), symptomatic hypotension, and angioedema
Measured: 8 weeks
Occurrences of adverse events of interest (time until occurrence)
Time until occurrence of specific adverse events, including decreased renal function (at least a 50% increase in serum creatinine or at least a 30% decrease in eGFR), hyperkalemia (serum potassium: 5.5 mEq/L or more), symptomatic hypotension, and angioedema
Measured: 8 weeks
Occurrences of other serious adverse events
Number of occurrences of other serious adverse events
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2021
- Study start27 Dec 2021
- Primary completion8 Feb 2024
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Saga University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Koichi Node, Saga University
- Investigators
- Koichi Node, Pr.,Dr., Principal investigator, Saga University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05164653
- Sponsor's protocol ID
- 00001
- Status last verified
- Aug 2024
- First submitted
- 17 Nov 2021
- Last updated
- 21 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nogi K, Tanaka A, Imai T, Doi S, Kamishita K, Kawai H, Obokata M, Kida K, Matsue Y, Izawa H, Hikoso S, Node K; PREMIER Study Investigators. Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: insights from the PREMIER study. Am Heart J. 2026 Aug 1:107549. doi: 10.1016/j.ahj.2026.107549. Online ahead of print.
PubMed 42542200Doi S, Tanaka A, Kida K, Imai T, Ueda Y, Nakano Y, Kizaki Y, Fukuda D, Matsue Y, Akashi YJ, Node K; PREMIER Study Investigators. Uptitration of Sacubitril/Valsartan in Acute Heart Failure: Insight from the PREMIER Study. J Card Fail. 2026 Mar;32(3):573-582. doi: 10.1016/j.cardfail.2025.05.001. Epub 2025 May 17.
PubMed 40389107Tanaka 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.
PubMed 39215531
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-initiated, Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint Study to Assess the Effect of In-hospital Initiation of Sacubitril Valsartan on the NT-proBNP Concentrations in Patients Admitted Due to Acute Exacerbation of Heart Failure (PREMIER)
- ClinicalTrials.gov ID
- NCT05164653
- Acronym / sponsor ID
- 00001
- Conditions
- Heart Failure
- Keywords
- Acute decompensated heart failure, Heart failure hospitalization, Sacubitril valsartan, NT-proBNP
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Saga UniversityUniversity, hospital or other
- Study start
- 27 Dec 2021 (actual)
- Primary completion
- 8 Feb 2024 (actual)
- Study completion
- Mar 2025 (estimated)
- First posted
- 21 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril Valsartan Sodium Hydrate | Experimental | Drug: Sacubitril Valsartan Sodium HydrateEntresto® Tablets |
| No Sacubitril Valsartan Sodium Hydrate | Active comparator | Drug: Standard treatmentStandard treatment for HF (ARB, ACE inhibitor etc.) |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril Valsartan Sodium HydrateAlso: Entresto® Tablets, Novartis Pharma K.K.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. | Drug | Sacubitril Valsartan Sodium Hydrate |
| Standard treatmentAlso: Angiotensin Converting Enzyme(ACE) inhibitor or Angiotensin II Receptor Blocker(ARB) etc.Standard treatment, other than Sacubitril Valsartan Sodium Hydrate, for HF | Drug | No Sacubitril Valsartan Sodium Hydrate |
Primary outcome
Proportional change in NT-proBNP concentrations from baseline to 8 weeks
Time frame: 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
108 secondary outcomes
Proportional change in NT-proBNP concentrations from baseline to 4 weeks
Time frame: 4 weeks
Reduction in NT-proBNP levels at 8 weeks
Time frame: 8 weeks
Reduction in NT-proBNP levels at 4 weeks
Time frame: 4 weeks
Mean reduction in NT-proBNP at 4 and 8 weeks
Time frame: 4 weeks, 8 weeks
Amount of change in biomarkers (cardiac troponin T)
Time frame: 8 weeks
Percent change in biomarkers (cardiac troponin T)
Time frame: 8 weeks
Amount of change in biomarkers (C-reactive protein)
Time frame: 8 weeks
Percent change in biomarkers (C-reactive protein)
Time frame: 8 weeks
Amount of change in biomarkers (growth differentiation factor 15)
Time frame: 8 weeks
Percent change in biomarkers (growth differentiation factor 15)
Time frame: 8 weeks
Amount of change in biomarkers (soluble suppression of tumorigenesis-2)
Time frame: 8 weeks
Percent change in biomarkers (soluble suppression of tumorigenesis-2)
Time frame: 8 weeks
Amount of change in biomarkers (glycoalbumin)
Time frame: 8 weeks
Percent change in biomarkers (glycoalbumin)
Time frame: 8 weeks
Amount of change in biomarkers (1.5-anhydro-D-glucitol)
Time frame: 8 weeks
Percent change in biomarkers (1.5-anhydro-D-glucitol)
Time frame: 8 weeks
Amount of change in clinical parameters (weight)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (weight)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (body mass index)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (body mass index)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (blood pressure)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (blood pressure)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (heart rate)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (heart rate)
Time frame: 4 weeks, 8 weeks
Amount of changs in clinical parameters (red blood cell)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (red blood cell)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (hemoglobin)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (hemoglobin)
Time frame: 4 weeks, 8 weeks
Amount of chang in clinical parameters (hematocrit)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (hematocrit)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (platelet)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (platelet)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (hemoglobin A1c)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (hemoglobin A1c)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (fasting glucose)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (fasting glucose)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (total cholesterol)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (total cholesterol)
Time frame: 4 weeks, 8 weeks
Amount of change in clinical parameters (high-density lipoprotein cholesterol)
Time frame: 4 weeks, 8 weeks
Percent change in clinical parameters (high-density lipoprotein cholesterol)
Time frame: 4 weeks, 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Derived from this study: PubMed 42542200Nogi K, Tanaka A, Imai T, Doi S, Kamishita K, Kawai H, Obokata M, Kida K, Matsue Y, Izawa H, Hikoso S, Node K; PREMIER Study Investigators. Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: insights from the PREMIER study. Am Heart J. 2026 Aug 1:107549. doi: 10.1016/j.ahj.2026.107549. Online ahead of print.
- Derived from this study: PubMed 40389107Doi S, Tanaka A, Kida K, Imai T, Ueda Y, Nakano Y, Kizaki Y, Fukuda D, Matsue Y, Akashi YJ, Node K; PREMIER Study Investigators. Uptitration of Sacubitril/Valsartan in Acute Heart Failure: Insight from the PREMIER Study. J Card Fail. 2026 Mar;32(3):573-582. doi: 10.1016/j.cardfail.2025.05.001. Epub 2025 May 17.
- Derived from this study: PubMed 39215531Tanaka 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.
Related trials for Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koichi Node, Pr.,Dr. principal investigator
Saga University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sacubitril Valsartan Sodium Hydrate and Standard treatment in people with Heart Failure, run by Saga University at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportional change in NT-proBNP concentrations from baseline to 8 weeks (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05164653, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.