Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List: a Multicenter, Double-blind, Randomized Clinical Trial.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Levels of suPAR (ng/ml)
研究概览
简要总结
In the DAPA-HF trial, the use of dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduced significantly the risk of worsening heart failure or death from cardiovascular causes compared to placebo among patients with heart failure (HF) and a reduced ejection fraction. This new drug offers a very potent and interesting therapeutic pathway since it reduces clinical congestion, it preserves glomerular renal function, does not appear to cause symptomatic clinical hypotension and improves symptoms and quality of life compared to placebo.
Advanced heart failure patients with reduced ejection fraction represent a small and severe subgroup of heart failure of patients with frequent worsening heart failure events and high rates of death. The effect of dapagliflozin in this subgroup of patients was not assessed in the DAPA-HF study. The therapeutic profile of SGLT2 inhibitors appears to be of high interest, since this group of patients has a poor tolerance to usual heart failure drugs, frequent worsening renal function and congestive symptoms persistence with poor quality of life scores.
Soluble urokinase-type plasminogen activator receptor (suPAR) is a signaling glycoprotein considered to be involved in the pathogenesis of kidney disease. It is associated with the risk of acute kidney injury in different clinical and experimental situation. It is also a new validated biomarker predictive of adverse clinical outcome in heart failure patients. This biomarker allows a better risk stratification in heart failure patients after adjustment for Nt-proBNP.
As a useful biomarker implicated in both heart failure and acute kidney injury, suPAR seems to be an interesting biomarker to assess cardio-renal benefits of dapagliflozin.
The aim of this study is to investigate if a treatment by dapagliflozin reduces significantly suPAR compared to placebo in a population of advanced heart failure patients, candidates to heart transplantation. The effect of dapagliflozin compared to placebo will also be assessed on other secondary heart failure outcomes in this patient population.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has signed informed consent form
- •Age ≥ 18 years
- •NYHA class ≥3
- •On optimal medical management (OMM) based on current heart failure practice guidelines at maximal tolerated dose for at least 30 days
- •On waiting list for heart transplantation after multidisciplinary Heart Team decision, with anticipated access to heart transplant ≥ 6 months
排除标准
- •Priority patient on waiting list for heart transplantation
- •Etiology of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy
- •Inotrope dependent, existence of ongoing mechanical circulatory support
- •Current acute decompensated HF or hospitalization due to decompensated HF <30 days prior to the enrolment
- •History of any organ transplant or prior implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization
- •Presence of an active, uncontrolled infection
- •Any recent interventional procedure likely to improve symptoms and heart failure status (coronary revascularization, percutaneous mitral valve intervention, cardiac resynchronization therapy) < 60 days
- •Glomerular filtration rate < 30 ml/min/1.73 m2, according to CKD-EPI formula
- •Unstable or rapidly progressing renal disease
- •Patients with severe hepatic impairment (Child-Pugh class C)
- •Chronic treatment with dapagliflozin or other SGLT2 inhibitors
- •Patient with known history of severe drug intolerance to dapagliflozin or any excipients of the dapagliflozin (galactose, lactase)
- •Type 1 diabetes mellitus
- •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug at investigators' discretion
- •Participation in another clinical interventional trial
- •Any condition other than heart failure that could limit survival to less than 24 months
- •Positive pregnancy test if of childbearing potential or refusal to use adequate contraception or women breast-feeding
- •Patients with any legal protection measure
- •Patients without any health coverage
- •Psychiatric disease/disorder, irreversible cognitive dysfunction or psychological issues that are likely to impair compliance
研究组 & 干预措施
Treatment group Daplagliflozin
干预措施: Dapagliflozin 10mg (Drug)
Control group
干预措施: Placebo (Drug)
结局指标
主要结局
Levels of suPAR (ng/ml)
时间窗: 6 months
次要结局
- pulmonary artery systolic and mean pressure assessed by right heart catheterization(6 months)
- pulmonary capillary wedge pressure assessed by right heart catheterization(6 months)
- mean pressure assessed by right heart catheterization(6 months)
- Left Ventricular Ejection Function assessed by echocardiography(6 months)
- Left ventricular end-diastolic diameter assessed by echocardiography(6 months)
- mitral regurgitation grade assessed by echocardiography(6 months)
- left atrial volume assessed by echocardiography(6 months)
- Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)(6 months)
- Creatinine level(6 months)
- Left ventricular end systolic volume assessed by echocardiography(6 months)
- Nt-proBNP level(6 months)
- VO2 max assessment(6 months)
- cardiac output assessed by right heart catheterization(6 months)
- right atrial pressure assessed by right heart catheterization(6 months)