Randomized Controlled Trial Evaluating the Impact of Mineralocorticoid Receptor Blockade by Eplerenone on Echocardiographic Abnormalities Among Kidney Graft Recipient Under Calcineurin Inhibitors. KT-CANOPY: Cardiac Improvement by Eplerenone Among Patients Under Cyclosporine or Tacrolimus for Kidney Transplantation.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 132
- 试验地点
- 3
- 主要终点
- Hierarchical composite endpoint (win ratio) : 1/ Death or hospitalization for heart failure or acute coronary syndrome, 2/ Variation in indexed left ventricular mass, 3/Variation in indexed left atrial volume.
研究概览
简要总结
The main objective of this research is to evaluate the effect, for 36 weeks, of eplerenone on abnormalities observed on cardiac ultrasound in patients with kidney transplantation for at least one year, under cyclosporine or tacrolimus. The intervention group will receive the usual standard treatment coupled with eplerenone for 36 weeks from randomization, while the control group will only receive the standard treatment. The main hypothesis is that anticalcineurins (cyclosporin or tacrolimus) lead to activation of the MR of vascular smooth muscle cells, vasoconstriction and vascular inflammation, which contributes to the persistence or recurrence of heart abnormalities in these patients after the initial post-transplant phase. The administration of eplerenone could antagonize this hyperactivation, reduce the cardiovascular effects of anticalcineurins and thus ultimately improve the cardiovascular prognosis of transplant patients.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female with 18 years old or older.
- •Transplant patient for at least one year.
- •Patient on long-term cyclosporine or tacrolimus.
- •Patient whose clinical situation has been stable for at least 3 months, without major treatment modification and without an episode of acute rejection.
- •Patient with renal function with a GFR (glomerular filtration rate) greater than or equal to 40 ml/min/1.73m
- •Patient with systolic blood pressure greater than or equal to 110 mmHg, with or without antihypertensive treatment.
- •Patient with the following echocardiographic abnormalities at baseline : an left ventricular mass > to 88 g/m2 in females or > to 102 g/m2 in males and/or left atrial volume > 34 ml/m2.
排除标准
- •Kidney transplant recipient more than 5 years post-transplantation.
- •Patient with permanent atrial fibrillation.
- •Patient with valvular heart disease (grade ≥ 3).
- •Patient considered to be at very high risk of mortality within the next year.
- •Patient with documented serum potassium ≥ 5.0 mmol/L within the previous month or receiving long-term potassium-binding resin therapy.
- •Patient with documented serum bicarbonate < 20 mmol/L within the previous month, with or without bicarbonate supplementation.
- •Patient receiving treatment with a mineralocorticoid receptor antagonist or having a formal indication for such treatment.
- •Patient receiving another potassium-sparing diuretic.
- •Patient receiving combined treatment with an ACE inhibitor and an angiotensin receptor blocker (each agent being permitted individually).
- •Patient receiving digoxin therapy.
- •Left ventricular ejection fraction (LVEF) < 40% on the baseline echocardiographic assessment.
- •Planned closure of an existing arteriovenous fistula within the following year.
- •Known hypersensitivity or allergy to eplerenone or any of its excipients.
- •Patient with severe hepatic impairment (Child-Pugh class C).
- •Patient currently receiving treatment with a strong CYP3A4 inhibitor (e.g., itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, or nefazodone).
- •Patient with known galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.
- •Patient with a contraindication to Kayexalate®: history of hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, or concomitant treatment with sorbitol-containing laxatives.
- •Woman of childbearing potential not using an effective method of contraception or planning to become pregnant within the next 12 months.
- •Patient participating in another interventional clinical study involving modifications to therapeutic management.
研究组 & 干预措施
Controle group (without eplerenone):
Standard treatment according to usual care, it can or cannot include a renin-angiotensin system blocker, left to the discretion of the physician in charge of the patient.
Intervention group (under Eplerenone):
Standard treatment according to usual care, combined with eplerenone for 36 weeks. Start of treatment with eplerenone at the initial dose of 25 mg/day, then adjusted according to clinical and biological tolerance: 12.5 mg/day (i.e., 25 mg/48h), 25 mg/day, and 50 mg/day.
干预措施: Eplerenone (Drug)
结局指标
主要结局
Hierarchical composite endpoint (win ratio) : 1/ Death or hospitalization for heart failure or acute coronary syndrome, 2/ Variation in indexed left ventricular mass, 3/Variation in indexed left atrial volume.
时间窗: at 36 weeks
次要结局
- Evolution of parameters of filling pressures (E/e')(at 36 weeks)
- Evolution of parameters of remodeling (left ventricular volume)(at 36 weeks)
- Evolution of Nt-ProBNP concentration(randomization, at 12 and 36 weeks)
- Evolution of collagen biomarkers (PICP )(at 36 weeks)
- Evolution of Biological markers of endothelial dysfunction (endothelin)(at 36 weeks)
- The occurrence of hyperkalaemia(at 36 weeks)
- Proportion of creatinine increase > 50%(at 36 weeks)
- Evolution of parameters of systolic function (LVEF, strain)(at 36 weeks)
- Evolution of peripheral systolic blood pressure (mmHg)(at 36 weeks)
- Evolution of peripheral diastolic blood pressure (mmHg)(at 36 weeks)
- Evolution of peripheral pulse pressure (mmHg)(at 36 weeks)
- Evolution of Graft function assessed with serum creatinine (micromol/L)(at 36 weeks)
- Evolution of proteinuria (mg/g)(at 36 weeks)
- Evolution of parameters of remodeling (left atrial volumes)(at 36 weeks)
- Evolution of collagen biomarkers ( PIIINP)(at 36 weeks)
- Evolution of Biological markers of endothelial dysfunction ( soluble endothelium selectin)(at 36 weeks)
- Evolution of Biological markers of endothelial dysfunction (von Willebrand factor)(at 36 weeks)
- Evolution of parameters of filling pressures (E-wave deceleration time).(at 36 weeks)
- Evolution of parameters of filling pressures (Systolic Pulmonary Artery Pressure (PAPs)).(at 36 weeks)
研究者
Pr. Nicolas GIRERD
Study chair
Central Hospital, Nancy, France