Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients: A Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 4
- 主要终点
- Left ventricular mass index
研究概览
简要总结
Background:
Calcimimetic therapy has been shown to reduce systemic FGF23 levels, which themselves are associated with left ventricular hypertrophy (LVH) in chronic kidney disease (CKD).
Methods/design:
This is a randomized multicenter trial in which the effect of etelcalcetide in comparison to alfacalcidol on LVH and cardiac fibrosis in hemodialysis patients with secondary hyperparathyroidism (sHPT) will be investigated.
The investigators will perform a comparative trial testing etelcalcetide vs. alfacalcidol treatment on top of conventional HPT therapy for 12 months. A total of 62 hemodialysis patients with sHPT and LVH will be enrolled in the study. After a washout of all calcimimetic and vitamin D treatment, subjects will be randomized at 1:1 ratio to either etelcalcetide or alfacalcidol. The participants will undergo cardiac imaging consisting of cardiac resonance imaging (cMRI) and strain echocardiography before and at baseline and one year. Etelcalcetide or alfacalcidol will be administered intravenously three times per week following chronic hemodialysis treatment.
The primary end point will be a change in left ventricular mass index (LVMI) measured in g/m2. As secondary end points the changes in left atrial diameter (LAD), cardiac fibrosis, wall motion abnormalities and left ventricular function, changes in serum FGF 23 and soluble Klotho levels as well as changes in proBNP as well as pre- and postdialysis troponin T (TnT) levels will be determined. Additionally a quantitative analysis of the treatment influence on the individual metabolites of the renin-angiotensin-aldosterone system (RAAS) will be performed using mass spectrometry ("RAAS fingerprint").
详细描述
Hypothesis and specific aims
In this randomized multicenter trial the investigators will study the effect of etelcalcetide in comparison to alfacalcidol on left ventricular hypertrophy and fibrosis in hemodialysis patients with secondary hyperparathyroidism (sHPT). Etelcalcetide is a calcimimetic drug that has been approved for the treatment of secondary HPT in hemodialysis patients.
Fibroblast growth factor 23 (FGF23) levels rise early in the development of chronic kidney disease (CKD) and recent studies have shown that FGF23 increases the development of left ventricular hypertrophy in these patients. Elevated FGF 23 levels are further associated with progression to end-stage renal disease, cardiac events and all-cause mortality. In animal models a blockade of FGF23 ameliorates the pathologic effect on left ventricular mass and function. Calcimimetic therapy has been shown to reduce systemic FGF23 levels, while vitamin D therapy is known to elevate FGF23. However, there is limited data on the clinical relevance of therapeutic modification of FGF23 levels in humans.
The investigators specifically hypothesize that treatment with etelcalcetide ameliorates pathological changes in cardiac structure in dialysis patients with sHPT by suppression of systemic FGF23 levels.
Specific aim 1
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
- Double (Participant, Outcomes Assessor)
盲法说明
Radiologist investigating the cMRI and physician performing the echocardiography will be blinded.
Patients will also be blinded
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
- •≥ 18 years of age
- •Treatment with maintenance hemodialysis 3 times a week for ≥ 3 months and ≤3 years
- •sHPT defined by
- •PTH levels obtained from the central laboratory of ≥300 pg/mL and no prior treatment with a calcimimetic drug, or
- •PTH levels obtained from the central laboratory of ≥300 pg/mL in patients under vitamin D treatment following a washout phase of 4 weeks
- •patients under treatment with cinacalcet who will be eligible following a washout phase of 4 weeks
- •serum calcium (corrected for serum albumin) levels obtained from the central laboratory of ≥ 2.08 mmol/L
- •Signs of LVH (increased myocardial thickness in the left ventricle, increased interventricular septum thickness i.e. ≥12mm) irrespective of signs of cardiac fibrosis in cardiac imaging (Echocardiography)
- •State of optimal fluid composition i.e. reaching the individual dry weight as measured with the help of a Body Composition Monitor (BCM) (more see below under section 4.9.2). Pulmonary edema will be excluded with the help of lung ultrasound (lung comet tails).
- •No substantial dose change of calcium supplements, phosphate binders, dialysate calcium, or active vitamin D for 4 weeks before screening
排除标准
- •Unstable medical condition based on medical history, physical examination, and routine laboratory tests, or judged unstable in the investigator's opinion
- •Significantly impaired left ventricular systolic function or significant, hemodynamically effective heart valve defects
- •History of any illness, which in the investigator's opinion, might confound the results of the study or pose additional risk
- •Anticipated parathyreoidectomy within 12 months after randomization
- •Scheduled date for kidney transplant from a living donor
- •Uncontrolled hyperphosphatemia
- •Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s)
- •Subject has known sensitivity or intolerance to any of the products to be administered for the purpose of this study
- •Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures
- •Subject is pregnant, or is of child-bearing potential and not using adequate contraceptive precautions although this is highly unlikely in patients on maintenance hemodialysis.
- •Contraindications for MRI (implanted MR-Unsafe - objects that are significantly ferromagnetic and pose a clear and direct threat to persons and equipment within the magnet room)
- •Overhydration as measured in BCM or visualized in lung ultrasound
结局指标
主要结局
Left ventricular mass index
时间窗: one year
Change of LVMI from baseline after a year-long treatment with either etelcalcetide or alfacalcidol. Measurement of LVMI (g/m2) with the help of cMRI
次要结局
- T-50-time measurement(one year)
- Cardiac structure(one year)
- Laboratory parameters(One year)
研究者
Rainer Oberbauer
Univ.-Prof. Rainer Oberbauer
Medical University of Vienna