Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure. A Proof of Concept Clinical Trial Within the EU FP 7 (European Union FP7) "HOMAGE" Programme " Heart OMics in AGing "
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 528
- 试验地点
- 9
- 主要终点
- Changes in serum concentrations of PIIINP
研究概览
简要总结
Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed. Prevention is most efficient when directed toward patients at risk and when mechanistically targeted to patients most likely to respond. An increase in myocardial and possibly vascular collagen content (fibrosis) may be a major determinant of the transition to HF. In patients with hypertension and diabetes, two important risk-factors for HF, changes in blood markers of fibrosis occur before clinically overt HF develops. These markers are also related to prognosis.
In the general population, Galectin-3 (Gal-3), a potential marker of fibrosis, is associated with cardiovascular (CV) risk factors, and predicts development of HF. In animal models, Gal-3 is a key mediator of aldosterone-induced CV and renal fibrosis and dysfunction.
The investigators hypothesize that the mineralocorticoid receptor antagonist (MRA), spironolactone, may prevent HF by acting on extracellular matrix remodelling, especially in patients with active fibrogenesis, identified by high Gal-3 levels. The benefit/risk ratio of spironolactone might be superior in patients with a higher compared to lower plasma concentrations of Gal-3.
Main objective is to investigate whether spironolactone can favourably alter extra-cellular matrix remodelling, assessed by changes in the fibrosis biomarker Procollagen Type III N-Terminal Peptide (PIIINP), in patients at increased risk of developing heart failure and whether this effect is greater in patients with increased plasma concentrations of Gal-3.
详细描述
The investigators hypothesize that the mineralocorticoid receptor antagonist (MRA), spironolactone, may prevent HF by acting on extracellular matrix remodelling, especially in patients with active fibrogenesis, identified by high Gal-3 levels. The benefit/risk ratio of spironolactone might be superior in patients with a higher compared to lower plasma concentrations of Gal-3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent will be obtained prior to any study procedure;
- •Age >60 years
- •Clinical risk factors for developing heart failure, either:
- •Coronary artery disease (h/o myocardial infarction, angioplasty or coronary artery bypass) Or
- •At least two of the following:
- •Diabetes Mellitus requiring Hypoglycaemic Pharmacotherapy
- •Receiving pharmacological treatment for Hypertension
- •Microalbuminuria
- •Abnormal ECG (left ventricular hypertrophy, QRS >120msec, abnormal Q-waves)
- •Biological risk: NT-pro-BNP values between 125 and 1,000 ng/L or BNP values between 35 and 280 pg/ml (consistent with ESC guidelines indicating risk of HF but helping to rule out prevalent HF or atrial fibrillation which are associated with marked increases in NT-proBNP/BNP and should be investigated)
排除标准
- •Recent wound healing/inflammation:
- •Surgical procedure, coronary, cerebral or peripheral vascular events or infection in the prior 3 months
- •Autoimmune disease
- •Hepatic Disease
- •Pre-existing diagnosis of clinical HF
- •Moderate/severe LV systolic ventricular dysfunction, i.e. LVEF <45%
- •Moderate or severe valve disease (investigators opinion)
- •eGFR< 30ml/min
- •Serum potassium >5.0 mmol/L
- •Treatment with an MRA or a loop diuretic (furosemide, bumetanide, ethacrynic acid or torasemide) in the previous three months
- •Potassium supplements or potassium-sparing diuretic at time of enrolment.
- •Atrial fibrillation within one month prior to inclusion (AF lasting <60 seconds on ambulatory ECG monitoring is permitted)
- •. History of hypersensitivity to spironolactone.
- •Requiring treatment with prohibited medication according to SmPC with exception of ACE inhibitors or angiotensin receptor blockers
- •Patients unable to give written informed consent.
- •Participation in another interventional trial in the preceding month
- •Ability to walk is, in the investigators opinion, clearly limited by joint disease or other locomotor problems rather than by cardiorespiratory fitness
研究组 & 干预措施
Spironolacton Group
Spironolacton Sandoz given 25mg daily oral use
干预措施: Spironolacton (Drug)
结局指标
主要结局
Changes in serum concentrations of PIIINP
时间窗: 9 months
mmol/l
次要结局
- changes in serum plasma levels of Biomarkers(9 months)
- Cardiac remodelling 1(9 months)
- Cardiac remodelling 3(9 months)
- Adverse events(screening, baseline, month1, month3, month 6, month 9)
- Cardiorespiratory performance during exercise(baseline, 9 months)
- Vascular function(screening, baseline, month1, month3, month 6, month 9)
- Cardiac remodelling 2(9 months)
- heart failure or AF(9 months)
- Worsening renal function(screening, baseline, month1, month3, month 6, month 9)
- Hyperkalemia(screening, baseline, month1, month3, month 6, month 9)