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临床试验/NCT05164653
NCT05164653进行中（未招募）4 期

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)

Saga University1 个研究点 分布在 1 个国家目标入组 400 人开始时间: 2021年12月27日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
进行中（未招募）
入组人数
400
试验地点
1
主要终点
Proportional change in NT-proBNP concentrations from baseline to 8 weeks
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
None

入排标准

年龄范围
20 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •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

排除标准

  • •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
  • •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)

研究组 & 干预措施

Sacubitril Valsartan Sodium Hydrate

Experimental

Entresto® Tablets

干预措施: Sacubitril Valsartan Sodium Hydrate (Drug)

No Sacubitril Valsartan Sodium Hydrate

Active Comparator

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

干预措施: Standard treatment (Drug)

结局指标

主要结局

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

时间窗: 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

次要结局

  • Amount of change in biomarkers (cardiac troponin T)(8 weeks)
  • Mean reduction in NT-proBNP at 4 and 8 weeks(4 weeks, 8 weeks)
  • Reduction in NT-proBNP levels at 4 weeks(4 weeks)
  • Percent change in biomarkers (C-reactive protein)(8 weeks)
  • Percent change in biomarkers (growth differentiation factor 15)(8 weeks)
  • Amount of change in biomarkers (growth differentiation factor 15)(8 weeks)
  • Proportional change in NT-proBNP concentrations from baseline to 4 weeks(4 weeks)
  • Reduction in NT-proBNP levels at 8 weeks(8 weeks)
  • Amount of change in biomarkers (C-reactive protein)(8 weeks)
  • Percent change in biomarkers (cardiac troponin T)(8 weeks)
  • Amount of change in biomarkers (soluble suppression of tumorigenesis-2)(8 weeks)
  • Percent change in biomarkers (soluble suppression of tumorigenesis-2)(8 weeks)
  • Amount of change in biomarkers (glycoalbumin)(8 weeks)
  • Amount of change in biomarkers (1.5-anhydro-D-glucitol)(8 weeks)
  • Percent change in clinical parameters (blood pressure)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (red blood cell)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (hemoglobin)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (hemoglobin A1c)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (total cholesterol)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (high-density lipoprotein cholesterol)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (non-high-density lipoprotein cholesterol)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (triglyceride)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (alanine aminotransferase)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (Fibrosis-4)(4 weeks, 8 weeks)
  • Percent change in biomarkers (glycoalbumin)(8 weeks)
  • Percent change in biomarkers (1.5-anhydro-D-glucitol)(8 weeks)
  • Amount of change in clinical parameters (weight)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (body mass index)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (body mass index)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (blood pressure)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (heart rate)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (heart rate)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (hemoglobin)(4 weeks, 8 weeks)
  • Amount of chang in clinical parameters (hematocrit)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (weight)(4 weeks, 8 weeks)
  • Amount of changs in clinical parameters (red blood cell)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (fasting glucose)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (aspartate aminotransferase)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (γ-glutamyl transpeptidase)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (uric acid)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (creatinine)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (sodium)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (potassium)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (estimated plasma volume)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (New York Heart Association class)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (platelet)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (non-high-density lipoprotein cholesterol)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (aspartate aminotransferase)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (creatinine)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (hematocrit)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (γ-glutamyl transpeptidase)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (potassium)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (New York Heart Association class)(4 weeks, 8 weeks)
  • Amount of change in echocardiographic parameters (left ventricular end-systolic volume)(8 weeks)
  • Percent change in echocardiographic parameters (left atrial volume index)(8 weeks)
  • Percent change in echocardiographic parameters (tricuspid regurgitation velocity)(8 weeks)
  • Percent change in clinical parameters (platelet)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (hemoglobin A1c)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (fasting glucose)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (total cholesterol)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (high-density lipoprotein cholesterol)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (triglyceride)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (alanine aminotransferase)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (uric acid)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (estimated glomerular filtration rate)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (estimated glomerular filtration rate)(4 weeks, 8 weeks)
  • Amount of change in clinical parameters (estimated plasma volume)(4 weeks, 8 weeks)
  • Percent change in echocardiographic parameters (left ventricular ejection fraction)(8 weeks)
  • Percent change in echocardiographic parameters (septal e')(8 weeks)
  • Percent change in echocardiographic parameters (flow velocity pattern through the mitral orifice (E))(8 weeks)
  • Amount of change in clinical parameters (sodium)(4 weeks, 8 weeks)
  • Percent change in clinical parameters (Fibrosis-4)(4 weeks, 8 weeks)
  • Amount of change in echocardiographic parameters (left ventricular end-diastolic volume)(8 weeks)
  • Percent change in echocardiographic parameters (left ventricular end-diastolic volume)(8 weeks)
  • Amount of change in echocardiographic parameters (left ventricular ejection fraction)(8 weeks)
  • Percent change in echocardiographic parameters (lateral e')(8 weeks)
  • Amount of change in echocardiographic parameters (left ventricular mass index)(8 weeks)
  • Amount of change in echocardiographic parameters (tricuspid regurgitation velocity)(8 weeks)
  • Amount of change in echocardiographic parameters(inferior vena cava diameter)(8 weeks)
  • Percent change in echocardiographic parameters (left ventricular end-systolic volume)(8 weeks)
  • Amount of change in echocardiographic parameters (septal e')(8 weeks)
  • Amount of change in echocardiographic parameters (lateral e')(8 weeks)
  • Amount of change in echocardiographic parameters (flow velocity pattern through the mitral orifice (E))(8 weeks)
  • Percent change in echocardiographic parameters (early mitral inflow velocity E and mitral annular early diastolic velocity e')(8 weeks)
  • Percent change in echocardiographic parameters (left ventricular mass index)(8 weeks)
  • Amount of change in echocardiographic parameters (global longitudinal strain)(8 weeks)
  • Amount of change in echocardiographic parameters (left atrial strain (2-chamber view and 4-chamber view))(8 weeks)
  • Amount of change in echocardiographic parameters (left ventricular outflow tract)(8 weeks)
  • Percent change in echocardiographic parameters (left ventricular outflow tract)(8 weeks)
  • Amount of change in echocardiographic parameters (left ventricular outflow tract velocity time integral)(8 weeks)
  • Percent change in echocardiographic parameters (left ventricular outflow tract velocity time integral)(8 weeks)
  • Percent change in echocardiographic parameters(inferior vena cava diameter)(8 weeks)
  • Percent change in echocardiographic parameters (left atrial strain (2-chamber view and 4-chamber view))(8 weeks)
  • Change in echocardiographic parameters (inferior vena cava diameter)(8 weeks)
  • Occurrences of the individual components of composite events and cardiovascular death (incidence of occurrences)(8 weeks)
  • Occurrences of adverse events of interest (total number of occurrences)(8 weeks)
  • Occurrences of adverse events of interest (time until occurrence)(8 weeks)
  • Amount of change in echocardiographic parameters (early mitral inflow velocity E and mitral annular early diastolic velocity e')(8 weeks)
  • Amount of change in echocardiographic parameters (left atrial volume index)(8 weeks)
  • Occurrences of the composite event of all-cause death or worsening heart failure events (incidence of occurrences)(8 weeks)
  • Occurrences of the individual components of composite events and cardiovascular death (total number of occurrences)(8 weeks)
  • Percent change in echocardiographic parameters (global longitudinal strain)(8 weeks)
  • Amount of change in Kansas City Cardiomyopathy Questionnaire-12 score(8 weeks)
  • Percentage of patients in Kansas City Cardiomyopathy Questionnaire-12 score(8 weeks)
  • Occurrences of the composite event of all-cause death or worsening heart failure events (total number of occurrences)(8 weeks)
  • Time to first occurrences of the composite event of all-cause death or worsening heart failure event(8 weeks)
  • Occurrences of the individual components of composite events and cardiovascular death (time until occurrence)(8 weeks)
  • Occurrences of other serious adverse events(8 weeks)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Koichi Node

Professor

Saga University

研究点 (1)

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