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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05164653
Recruitment Status : Recruiting
First Posted : December 21, 2021
Last Update Posted : January 26, 2023
Sponsor:
Information provided by (Responsible Party):
WDB Clinical Research Co., Ltd.

Tracking Information
First Submitted Date  ICMJE November 17, 2021
First Posted Date  ICMJE December 21, 2021
Last Update Posted Date January 26, 2023
Actual Study Start Date  ICMJE December 27, 2021
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2021)		 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2021)
  • Proportional change in NT-proBNP concentrations from baseline to 4 weeks [ Time Frame: 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
  • Reduction in NT-proBNP levels at 8 weeks [ Time Frame: 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
  • Reduction in NT-proBNP levels at 4 weeks [ Time Frame: 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
  • Mean reduction in NT-proBNP at 4 and 8 weeks [ Time Frame: 4 weeks, 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
  • Amount of change in biomarkers (cardiac troponin T) [ Time Frame: 8 weeks ]
    Amount of change in cardiac troponin T at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in biomarkers (cardiac troponin T) [ Time Frame: 8 weeks ]
    Percent change in cardiac troponin T at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in biomarkers (C-reactive protein) [ Time Frame: 8 weeks ]
    Amount of change in C-reactive protein at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in biomarkers (C-reactive protein) [ Time Frame: 8 weeks ]
    Percent change in C-reactive protein at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in biomarkers (growth differentiation factor 15) [ Time Frame: 8 weeks ]
    Amount of change in growth differentiation factor 15 at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in biomarkers (growth differentiation factor 15) [ Time Frame: 8 weeks ]
    Percent change in growth differentiation factor 15 at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in biomarkers (soluble suppression of tumorigenesis-2) [ Time Frame: 8 weeks ]
    Amount of change in soluble suppression of tumorigenesis-2 at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in biomarkers (soluble suppression of tumorigenesis-2) [ Time Frame: 8 weeks ]
    Percent change in soluble suppression of tumorigenesis-2 at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in biomarkers (glycoalbumin) [ Time Frame: 8 weeks ]
    Amount of change in glycoalbumin at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in biomarkers (glycoalbumin) [ Time Frame: 8 weeks ]
    Percent change in glycoalbumin at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in biomarkers (1.5-anhydro-D-glucitol) [ Time Frame: 8 weeks ]
    Amount of change in 1.5-anhydro-D-glucitol at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in biomarkers (1.5-anhydro-D-glucitol) [ Time Frame: 8 weeks ]
    Percent change in 1.5-anhydro-D-glucitol at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (weight) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in weight at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (weight) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in weight at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (body mass index) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in body mass index at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (body mass index) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in body mass index at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (blood pressure) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in systolic blood pressure and diastolic blood pressure at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (blood pressure) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in systolic blood pressure and diastolic blood pressure at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (heart rate) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in heart rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (heart rate) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in heart rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of changs in clinical parameters (red blood cell) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in red blood cell at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (red blood cell) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in red blood cell at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (hemoglobin) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in hemoglobin at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (hemoglobin) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in hemoglobin at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of chang in clinical parameters (hematocrit) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in hematocrit at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (hematocrit) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in hematocrit at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (platelet) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in platelet at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (platelet) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in platelet at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (hemoglobin A1c) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in hemoglobin A1c at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (hemoglobin A1c) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in hemoglobin A1c at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (fasting glucose) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in fasting glucose at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (fasting glucose) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in fasting glucose at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (total cholesterol) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in total cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (total cholesterol) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in total cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (high-density lipoprotein cholesterol) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (high-density lipoprotein cholesterol) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (non-high-density lipoprotein cholesterol) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in non-high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (non-high-density lipoprotein cholesterol) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in non-high-density lipoprotein cholesterol at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (triglyceride) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in triglyceride at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (triglyceride) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in triglyceride at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (aspartate aminotransferase) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in aspartate aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (aspartate aminotransferase) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in aspartate aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (alanine aminotransferase) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in alanine aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (alanine aminotransferase) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in alanine aminotransferase at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (γ-glutamyl transpeptidase) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in γ-glutamyl transpeptidase at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (γ-glutamyl transpeptidase) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in γ-glutamyl transpeptidase at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (uric acid) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in uric acid at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (uric acid) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in uric acid at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (creatinine) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in creatinine at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (creatinine) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in creatinine at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (estimated glomerular filtration rate) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in estimated glomerular filtration rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (estimated glomerular filtration rate) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in estimated glomerular filtration rate at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (sodium) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in sodium at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (sodium) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in sodium at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (potassium) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in potassium at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (potassium) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in potassium at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (Fibrosis-4) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in Fibrosis-4 at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (Fibrosis-4) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in Fibrosis-4 at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (estimated plasma volume) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in estimated plasma volume at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (estimated plasma volume) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in estimated plasma volume at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in clinical parameters (New York Heart Association class) [ Time Frame: 4 weeks, 8 weeks ]
    Amount of change in New York Heart Association class at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in clinical parameters (New York Heart Association class) [ Time Frame: 4 weeks, 8 weeks ]
    Percent change in New York Heart Association class at 4 and 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left ventricular end-diastolic volume) [ Time Frame: 8 weeks ]
    Amount of change in left ventricular end-diastolic volume at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left ventricular end-diastolic volume) [ Time Frame: 8 weeks ]
    Percent change in left ventricular end-diastolic volume at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left ventricular end-systolic volume) [ Time Frame: 8 weeks ]
    Amount of change in left ventricular end-systolic volume at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left ventricular end-systolic volume) [ Time Frame: 8 weeks ]
    Percent change in left ventricular end-systolic volume at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left ventricular ejection fraction) [ Time Frame: 8 weeks ]
    Amount of change in left ventricular ejection fraction at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left ventricular ejection fraction) [ Time Frame: 8 weeks ]
    Percent change in left ventricular ejection fraction at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (septal e') [ Time Frame: 8 weeks ]
    Amount of change in septal e' at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (septal e') [ Time Frame: 8 weeks ]
    Percent change in septal e' at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (lateral e') [ Time Frame: 8 weeks ]
    Amount of change in lateral e' at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (lateral e') [ Time Frame: 8 weeks ]
    Percent change in lateral e' at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (flow velocity pattern through the mitral orifice (E)) [ Time Frame: 8 weeks ]
    Amount of change in flow velocity pattern through the mitral orifice (E) at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (flow velocity pattern through the mitral orifice (E)) [ Time Frame: 8 weeks ]
    Percent change in flow velocity pattern through the mitral orifice (E) at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (early mitral inflow velocity E and mitral annular early diastolic velocity e') [ Time Frame: 8 weeks ]
    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
  • Percent change in echocardiographic parameters (early mitral inflow velocity E and mitral annular early diastolic velocity e') [ Time Frame: 8 weeks ]
    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
  • Amount of change in echocardiographic parameters (left ventricular mass index) [ Time Frame: 8 weeks ]
    Amount of change in left ventricular mass index at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left ventricular mass index) [ Time Frame: 8 weeks ]
    Percent change in left ventricular mass index at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left atrial volume index) [ Time Frame: 8 weeks ]
    Amount of change in left atrial volume index at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left atrial volume index) [ Time Frame: 8 weeks ]
    Percent change in left atrial volume index at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left ventricular outflow tract) [ Time Frame: 8 weeks ]
    Amount of change in left ventricular outflow tract at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left ventricular outflow tract) [ Time Frame: 8 weeks ]
    Percent change in left ventricular outflow tract at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left ventricular outflow tract velocity time integral) [ Time Frame: 8 weeks ]
    Amount of change in left ventricular outflow tract velocity time integral at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left ventricular outflow tract velocity time integral) [ Time Frame: 8 weeks ]
    Percent change in left ventricular outflow tract velocity time integral at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (tricuspid regurgitation velocity) [ Time Frame: 8 weeks ]
    Amount of change in tricuspid regurgitation velocity at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (tricuspid regurgitation velocity) [ Time Frame: 8 weeks ]
    Percent change in tricuspid regurgitation velocity at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters(inferior vena cava diameter) [ Time Frame: 8 weeks ]
    Amount of change in inferior vena cava diameter at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters(inferior vena cava diameter) [ Time Frame: 8 weeks ]
    Percent change in inferior vena cava diameter at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (global longitudinal strain) [ Time Frame: 8 weeks ]
    Amount of change in global longitudinal strain at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (global longitudinal strain) [ Time Frame: 8 weeks ]
    Percent change in global longitudinal strain at 8 weeks after protocol treatment initiation compared with baseline
  • Amount of change in echocardiographic parameters (left atrial strain (2-chamber view and 4-chamber view)) [ Time Frame: 8 weeks ]
    Amount of change in left atrial strain (2-chamber view and 4-chamber view) at 8 weeks after protocol treatment initiation compared with baseline
  • Percent change in echocardiographic parameters (left atrial strain (2-chamber view and 4-chamber view)) [ Time Frame: 8 weeks ]
    Percent change in left atrial strain (2-chamber view and 4-chamber view) at 8 weeks after protocol treatment initiation compared with baseline
  • Change in echocardiographic parameters (inferior vena cava diameter) [ Time Frame: 8 weeks ]
    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
  • Amount of change in Kansas City Cardiomyopathy Questionnaire-12 score [ Time Frame: 8 weeks ]
    Amount of change in Kansas City Cardiomyopathy Questionnaire-12 score at 8 weeks after protocol treatment initiation compared with baseline
  • Percentage of patients in Kansas City Cardiomyopathy Questionnaire-12 score [ Time Frame: 8 weeks ]
    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
  • Time to first occurrences of the composite event of all-cause death or worsening heart failure event [ Time Frame: 8 weeks ]
    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)
  • Occurrences of the composite event of all-cause death or worsening heart failure events (total number of occurrences) [ Time Frame: 8 weeks ]
    Total number of occurrences of the composite event of all-cause death or worsening heart failure events (first and recurrence)
  • Occurrences of the composite event of all-cause death or worsening heart failure events (incidence of occurrences) [ Time Frame: 8 weeks ]
    Incidence of occurrences of the composite event of all-cause death or worsening heart failure events (first and recurrence)
  • Occurrences of the individual components of composite events and cardiovascular death (total number of occurrences) [ Time Frame: 8 weeks ]
    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
  • Occurrences of the individual components of composite events and cardiovascular death (incidence of occurrences) [ Time Frame: 8 weeks ]
    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
  • Occurrences of the individual components of composite events and cardiovascular death (time until occurrence) [ Time Frame: 8 weeks ]
    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
  • Occurrences of adverse events of interest (total number of occurrences) [ Time Frame: 8 weeks ]
    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
  • Occurrences of adverse events of interest (time until occurrence) [ Time Frame: 8 weeks ]
    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
  • Occurrences of other serious adverse events [ Time Frame: 8 weeks ]
    Number of occurrences of other serious adverse events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Program of Angiotensin-Neprilysin Inhibition in Admitted Patients With Worsening Heart Failure (PREMIER)
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure
Intervention  ICMJE
  • Drug: 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.

    Other Name: Entresto® Tablets, Novartis Pharma K.K.
  • Drug: Standard treatment
    Standard treatment, other than Sacubitril Valsartan Sodium Hydrate, for HF
    Other Name: Angiotensin Converting Enzyme(ACE) inhibitor or Angiotensin II Receptor Blocker(ARB) etc.
Study Arms  ICMJE
  • Experimental: Sacubitril Valsartan Sodium Hydrate
    Entresto® Tablets
    Intervention: Drug: Sacubitril Valsartan Sodium Hydrate
  • Active Comparator: No Sacubitril Valsartan Sodium Hydrate
    Standard treatment for HF (ARB, ACE inhibitor etc.)
    Intervention: Drug: Standard treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 20, 2021)		 400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2025
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michihiro Shimizu +81-3-5144-2270 shimizu@wdbrinken.co.jp
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05164653
Other Study ID Numbers  ICMJE 00001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party WDB Clinical Research Co., Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE WDB Clinical Research Co., Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Koichi Node, Pr.,Dr. Saga University Hospital
PRS Account WDB Clinical Research Co., Ltd.
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP