Use of ETElcalcetidefor pReserving vitamiN K-dependent proteIn activiTY ITAlian Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 主要终点
- Levels of VKDP
研究概览
简要总结
The goal of this Prospective Observational Study of comparative effectiveness is to provide real world evidence of the effect of Etelcalcetide in increasing actives form VKDPs levels such as BGP and MGP at 3, 9 and 18 months from baseline, with resulting correct bone mineralization and inhibition vascular calcification in hemodialysis patients.
The study will enroll 160 hemodialysis patients: 80 patients treated with Etelcalcetide and 80 age and sex matched patients treated with Calcitriol or vitamin D analogs. The treating nephrologist will base the target dose of Etelcalcetide on individual-level in order to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). The main endpoint is the comparison of the levels of active forms of VKDP (MGP and BGP) between patients treated with Etelcalcetide and those treated with vitamin D or vitamin D analogues. The measurements of the biomarkers are scheduled at baseline and after 3, 9, and 18 months.
详细描述
Vascular calcifications (VCs) are frequent complications of chronic kidney disease (CKD), and mineral disorders are associated with aortic calcifications and increased risk of bone fractures. The complex pathogenesis of VCs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key inhibitors, such as vitamin K-dependent proteins (VKDPs) like matrix Gla protein (MGP) play pivotal roles in VCs development. Traditional treatments to reduce VC focus on lowering PTH, calcium and phosphorus levels and etelcalcetide revealed as a promising therapy to this scope. Accordingly, the VItamin K Italian study (VIKI) reported that calcimimetics treated hemodialysis patients had higher levels of total BGP and MGP versus those untreated, suggesting a protective effect of this drugs class. These findings point out the multifactorial nature of VC in CKD and suggest new treatment strategies and targeted pathways for improving outcomes. The ETERNITY-ITA study will investigate the real world effect of Etelcalcetide in increasing actives form VKDPs levels such as BGP and MGP thus contributing to bone and vascular health in hemodialysis patients. ETERNITY-ITA is a multi-center comparative effectiveness, observational, longitudinal study. The study will enroll 160 hemodialysis patients: 80 patients treated with Etelcalcetide and 80 age and sex matched patients treated with Calcitriol or vitamin D analogs. The treating nephrologist will base the target dose of Etelcalcetide on individual-level in order to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). The main endpoint is the comparison of the levels of active forms of VKDP (MGP and BGP) between patients treated with Etelcalcetide and those treated with vitamin D or vitamin D analogues. The measurements of the biomarkers are scheduled at baseline and after 3, 9, and 18 months.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 provided informed consent;
- •Patient is 18 years of age or older of both gender;
- •Patients receiving maintenance HD three times per week (Kt/V >1.2);
- •Parathyroid hormone concentrations >500 ng/l at screening, or if parathyroidectomy is planned or expected, Ca >8.3 mg/dl;
- •Will be considered patients in the exposed group:
- •Patients who have started Etelcalcetide within 1-month before the study enrolment;
- •Patients naïve to intravenous calcimimetics use;
- •Patients who have suspended oral calcimimetics from at least 1-month;
- •Patients who are not responder or not compliant to the treatment with calcitriol;
- •In the unexposed group, patients on treatment with calcitriol or vitamin D analogs and who are age (± 2 years) and sex comparable (matching) to those in the exposed group will be considered;
- •Native vitamin D can be used in both groups and should be administered to target a 25(OH)D level > 30 ng/ml;
- •Dialysate calcium concentration must be stable for at least 4 weeks prior to screening laboratory assessments;
- •Patient must have severe HPT as defined by two laboratory screening pre-dialysis serum PTH values > 500 pg/ml, measured on two consecutive lab checks prior to entering the study. PTH levels should be standardized according to the following table (Souberbielle et al. Kidney Int 2010);
- •Total alkaline phosphatase greater than the normal range, or even within the normal range but if greater than the tertile of the reference range for the assay;
- •Patients will be eligible only if they will show at least a moderate Aorta VCs and/or Iliac arteries VCs and at least a mild VF.
排除标准
- •Previous treatment with oral calcimimetics (cinacalcet) must have been suspended for at least 30 days. Recent start of calcimimetics (Etelcalcetide) is acceptable, but patients are excluded if treatment lasts for more than 1 month;
- •Patients has received a bisphosphonate, denosumab or teriparatide during the 12 months prior to screening;
- •The patient underwent parathyroidectomy in the 6 months before the start of the study or if scheduled soon;
- •Scheduled kidney transplant during the study period or anticipated living donor evaluation within three months of recruitment;
- •Patient has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator;
- •Metabolic bone diseases not related to the kidney (i.e., Pagets, Osteogenesis Imprefecta);
- •Severe untreated hyperthyroidism;
- •Malignancy within the last 3 years (except non-melanoma skin cancers or cervical carcinoma in situ);
- •Patient is pregnant or nursing;
- •Patients with Long QT Syndrome;
- •Patient likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient and Investigator's knowledge.
结局指标
主要结局
Levels of VKDP
时间窗: Baseline and after 3, 9, and 18 months of treatment
The primary endpoint is the comparison of the levels of active forms of VKDP between patients treated with Etelcalcetide and those treated with vitamin D or vitamin D analogues (MGP and BGP).
次要结局
- Hematocrit (Ht)(Baseline, 3, 9 and 18-months)
- Plates (PLTS)(Baseline, 3, 9 and 18-months)
- Reticulocytes(Baseline, 3, 9 and 18-months)
- Calcium(Baseline, 3, 9 and 18-months)
- Phosphate(Baseline, 3, 9 and 18-months)
- PTH(Baseline, 3, 9 and 18-months)
- 25(OH)D(Baseline, 3, 9 and 18-months)
- P1NP(Baseline, 3, 9 and 18-months)
- CTX(Baseline, 3, 9 and 18-months)
- TRAP 5b(Baseline, 3, 9 and 18-months)
- BSAP(Baseline, 3, 9 and 18-months)
- DKK1(Baseline, 3, 9 and 18-months)
- Irisin(Baseline, 3, 9 and 18-months)
- Ferritin(Baseline, 3, 9 and 18-months)
- KT/V(Baseline, 3, 9 and 18-months)
- Aluminium(Baseline, 3, 9 and 18-months)
- Cholesterol(Baseline, 3, 9 and 18-months)
- Triglycerides(Baseline, 3, 9 and 18-months)
- Magnesium(Baseline, 3, 9 and 18-months)
- Klotho(Baseline, 3, 9 and 18-months)
- ALP(Baseline, 3, 9 and 18-months)
- cFGF23(Baseline, 3, 9 and 18-months)
- Sclerostin(Baseline, 3, 9 and 18-months)
- Fetuin A(Baseline, 3, 9 and 18-months)
- Zinc(Baseline, 3, 9 and 18-months)
- Serum Calcification Propensity T50 test(Baseline, 3, 9 and 18-months)
- Hemoglobin (Hb)(Baseline, 3, 9 and 18-months)
- Iron(Baseline, 3, 9 and 18-months)
- Transferrin Saturation(Baseline, 3, 9 and 18-months)
- Albumin(Baseline, 3, 9 and 18-months)
- Transferrin(Baseline, 3, 9 and 18-months)
- C-reactive Protein (CRP)(Baseline, 3, 9 and 18-months)
- Association between Verterbal Fractures and Vascular Calcificatiom(Baseline, 18-months)
- Novel quantitative computer-assisted scoring method for vascular calcifications.(Baseline, 18-months)
- Vertebral Fractures(Baseline, 18-months)
- Cholesterol LDL(Baseline, 3, 9 and 18-months)
- BMD: Bone Mineral Density(Baseline, 18-months)
- Cholesterol HDL(Baseline, 3, 9 and 18-months)
- Vascular Calcification(Baseline, 18-months)
- Effect of Etelcalcetide on cardiovascular events and all-cause mortality.(Baseline, 18-months)
- Etelcalcetide Safety: Number of participants with treatment-related adverse events.(Baseline, 18-months)