Secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis therapy.
Conditions
Interventions
Trade Name: Parsabiv
Product Name: Etelcalcetide
Pharmaceutical Form: Injection
INN or Proposed INN: ETELCALCETIDE
Other descriptive name: AMG 416
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • = 18 years of age • Treatment with maintenance hemodialysis 3 times a week for = 3 months and =3 years • sekundary hyperparathyroidism defined by o Parathyroid hormone levels obtained from the central laboratory of =300 pg/mL and no prior treatment with a calcimimetic drug, or o patients under treatment with cinacalcet who will be eligible following a washout phase of 4 weeks • serum calcium levels obtained from the central laboratory of = 2.08 mmol/L • Signs of left ventricular hypertrophy (increased myocardial thickness in the left ventricle, increased intraventricular septum thickness) +/- 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. 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 4 weeks before screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: • 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 6 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 • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In this randomized, multicenter trial we will study the effect of etecalcitide versus alfacalcidol on left ventricular hypertrophy (LVH) and fibrosis in hemodialysis patients with secondary hyperparathyroidism (sHPT). Etecalcitide is a calcimimetic drug that has been approved for the treatment of sHPT in dialysis patients. FGF23 increases the development of LVH in these patients and is 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 increases it. However, there is limited data on the clinical relevance of therapeutic modification of FGF23 levels in humans. We hypothesize that treatment with etelcalcetide ameliorates pathological changes in cardiac structure in dialysis patients with sHPT by suppression of systemic FGF23 levels.;Secondary Objective: Cardiac structure apart from left ventricular hypertrophy, i.e. Left atrial diameter, cardiac fibrosis, wall motion abnormalities and left ventricular function compared in the etelcalcetide vs. alfacalcidol group. Laboratory parameters: electrolytes, PTH, BNP, troponin T (pre and postdialysis), FGF23, soluble klotho levels. Analysis of the renin-angiotensin-aldosterone system (“RAAS fingerprint”);Primary end point(s): In this trial we will determine the influence of calcimimetic therapy versus vitamin D therapy on left ventricular hypertrophy in hemodialysis patients with secondary hyperparathyroidism (HPT): We will perform a trial testing etecalcitide treatment vs alfacalcidol on top of conventional HPT therapy (phosphate binders, calcium substituation) for 12 months. Etecalcitide 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 m | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): As secondary end points we will measure changes in left atrial diameter, cardiac fibrosis, wall motion abnormalities and left ventricular function (in cardiac MRI as well as strain echocardiography) as well as changes in electrolytes, PTH, BNP, troponin T (pre and post dialysis), serum FGF 23 and soluble Klotho levels. Additionally, the renin-angiotensin-aldosterone system (RAAS) metabolites will be analyzed with the help of mass spectrometry (“RAAS fingerprint”).;Timepoint(s) of evaluation of this end point: Cardiac MRI and echocardiography with strain will be performed at baseline as well as after 12 months of therapy. Laboratory tests will be performed multiple times in clearly defined intervalls. RAAS fingerprint will be performed at baseline as well as after 12 months of therapy. | — |
Countries
Austria
Contacts
Public ContactAmgen Europe B.V.
Amgen Europe B.V. BREDA
Outcome results
None listed