NCT03030235已完成4 期
Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With PRESERVED Ejection Fraction Heart Failure
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 324
- 试验地点
- 26
- 主要终点
- Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Summary Score (KCCQ-CS)
研究概览
简要总结
The primary purpose of this study is to evaluate the impact of dapagliflozin, as compared with placebo, on heart failure, disease specific biomarkers, symptoms, health status and quality of life in patients with chronic heart failure with preserved systolic function.
详细描述
A 12-week randomized, double-blind, placebo-controlled trial to evaluate the effects of once-daily dapagliflozin 10 mg on heart failure disease-specific biomarkers (NTproBNP and BNP), symptoms, health status, and quality of life in patients with chronic heart failure with preserved systolic function. An imaging substudy will also be conducted to explore the effects of dapagliflozin vs. placebo on various echocardiographic parameters.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 119 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
- •Ejection fraction (EF) ≥ 45% as determined on imaging study within 24 months of enrolment with no change in clinical status suggesting potential for deterioration in systolic function
- •Elevated NT-proBNP (≥ 225 pg/ml) or BNP (≥ 75 pg/ml). For patients with permanent atrial fibrillation inclusion thresholds will be BNP ≥ 100 pg/mL or NTproBNP ≥ 375 pg/mL
- •Stable medical therapy for heart failure for 15 days as defined by: i. No addition or removal of ACE, angiotensin receptor blockers (ARBs), valsartan/sacubitril, beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists; ii.No substantial change in dosage (100% or greater increase or decrease from baseline dose) of ACE, ARBs, beta-blockers, CCBs or aldosterone antagonists
- •On a diuretic ≥15 days prior to screening visit and a stable diuretic therapy for 7 days
- •At least one of the following: i. Hospitalization for decompensated HF in the last 12 months; ii. Acute treatment for HF with intravenous loop diuretic or hemofiltration in the last 12 months; iii. Mean pulmonary capillary wedge pressure ≥15 mmHg or LV end diastolic pressure (LVEDP) ≥15 mmHg documented during catheterization at rest, or pulmonary capillary wedge pressure or LVEDP ≥25 mmHg documented during catheterization with exercise; iv. Structural heart disease evidenced by at least one of the following echo findings (any local measurement made within the 24 months prior to screening visit): a) left atrial (LA) enlargement defined by at least one of the following: LA width ≥3.8cm or LA length ≥5.0 cm or LA area ≥20 cm2 or LA volume ≥55 mL or LA volume index ≥29 mL/m2 b) or left ventricular hypertrophy (LVH) defined by septal thickness or posterior wall thickness ≥1.1 cm.
排除标准
- •Decompensated heart failure (hospitalization for heart failure within 7 days prior to screening)
- •History of type 1 diabetes
- •History of diabetic ketoacidosis
- •Estimated glomerular filtration rate (eGFR) < 20 at the screening visit by modified MDRD equation GFR (mL/min/1.73 m2 ) = 175 x (Scr) -1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American)
- •Admission for an acute coronary syndrome (ST-elevation MI, non-ST-elevation MI, or unstable angina), percutaneous coronary intervention, or cardiac surgery within 30 days prior to the screening visit.
- •Admission for cardiac resynchronization therapy (CRT) within 90 days prior to the screening visit.
- •Planned cardiovascular revascularization (percutaneous intervention or surgical) or major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy, or transcatheter aortic valve replacement) or CRT within the 90 days after the screening visit.
- •Participation in any interventional clinical trial (with an investigational drug or device) that is not an observational registry within 15 days of the screening visit.
- •History of hypersensitivity to dapagliflozin
- •For women of child-bearing potential: Current or planned pregnancy or currently lactating.
- •Life expectancy <1 year at the screening visit
- •Patients who are volume depleted based upon physical examination at the time of the screening or randomization visit
- •BNP <75 pg/mL and NTproBNP<225 pg/mL at the screening visit. For patients with permanent atrial fibrillation exclusion thresholds will be BNP<100 pg/mL and NTproBNP<375pg/mL.
- •Patients currently being treated with any SGLT-2 inhibitor (dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) or having received treatment with any SGLT-2 inhibitor within the 12 weeks prior to the screening visit.
- •Average supine systolic BP <100 mmHg at the screening or randomization visit
- •Current history of bladder cancer
- •Donation of blood or bone marrow 12 weeks prior to the screening visit and no planned donations during the study period
- •Heart failure due to restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe stenotic valve disease, and HOCM (hypertrophic obstructive cardiomyopathy).
- •Heart failure due to severe aortic or mitral regurgitation
- •Severe COPD thought to be a primary contributor to dyspnea
- •Isolated right heart failure due to pulmonary disease
- •Active and significant ischemia thought to be a primary contributor to dyspnea
- •Documentation of previous EF < 45%, under stable conditions, within the past 36 months
- •Complex congenital heart disease
- •Uncontrolled hypertension, defined as systolic blood pressure ≥200 mmHg during the screening visit (average value of three blood pressure measurements obtained in supine position)
- •Any other condition that in the judgment of the investigator would jeopardize the patient's participation in the study or that may interfere with the interpretation of study data or if the patient is considered unlikely to comply with study procedures, restrictions and requirements
- •Bariatric surgery within the past 6 months or planned bariatric surgery within the study time course.
- •CardioMems device implantation within previous 4 weeks or planned CardioMems implantation during study period
- •For echo substudy only: patients with ventricular paced rhythm or left bundle branch block on the most recent clinically available 12-lead electrocardiogram.
- •For echo substudy only: permanent atrial fibrillation
研究组 & 干预措施
Dapagliflozin
Active Comparator
Dapagliflozin 10 mg oral tablet, once daily, for 12 weeks
干预措施: Dapagliflozin 10Mg Oral Tablet (Drug)
Placebo
Placebo Comparator
Dapagliflozin matching placebo oral tablet, once daily, for 12 weeks
干预措施: Dapagliflozin matching placebo (Drug)
结局指标
主要结局
Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Summary Score (KCCQ-CS)
时间窗: Baseline to Week 12
Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CS) at Week 12. The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ-CS, a small but clinically meaningful change is considered to be ≥ 5 points. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.
次要结局
- Effect of Dapagliflozin, as Compared With Placebo, on 6 Minute Walk Test Distance(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Brain Natriuretic Peptide (BNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Proportion of Patients With ≥ 5 Point Increase in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) and ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide(NTproBNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Weight(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Hemoglobin A1c(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on the Proportion of Patients With a ≥ 5 Point Increase in KCCQ Clinical Summary Score (KCCQ-CS) and KCCQ Overall Summary Score (KCCQ-OS)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on N-terminal Pro B-type Natriuretic Peptide (NTproBNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on the Proportion of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP)(Baseline to Week 12)
- Effect of Dapagliflozin, as Compared With Placebo, on Systolic Blood Pressure(Baseline to Week 12)
研究者
研究点 (26)
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