Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients (EtECAR-HD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03182699
Recruitment Status : Completed
First Posted : June 9, 2017
Last Update Posted : June 9, 2020
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Rainer Oberbauer, Medical University of Vienna

Brief Summary:

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").


Condition or disease Intervention/treatment Phase
Secondary Hyperparathyroidism Chronic Kidney Disease Requiring Chronic Dialysis Left Ventricular Hypertrophy Diagnostic Test: cardiac MRI Diagnostic Test: echocardiography with strain Diagnostic Test: Laboratory tests Diagnostic Test: Body composition monitoring Diagnostic Test: lung ultrasound Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Masking Description:

Radiologist investigating the cMRI and physician performing the echocardiography will be blinded.

Patients will also be blinded

Primary Purpose: Treatment
Official Title: Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients: A Randomized Controlled Trial
Actual Study Start Date : October 1, 2017
Actual Primary Completion Date : December 20, 2019
Actual Study Completion Date : December 20, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis

Arm Intervention/treatment
Experimental: Etelcalcetide
Patients will receive Etelcalcetide i.v. 3 times per week after dialysis Dose titration will take plac every 4 weeks in the first 16 weeks Dose adaptation is based on PTH, SerumCa++, SerumPhosphate, T-50-time
Diagnostic Test: cardiac MRI
non contrast heart MRI at baseline and after 1 year of therapy

Diagnostic Test: echocardiography with strain
echocardiography at baseline and after 1 year of therapy

Diagnostic Test: Laboratory tests
drawing blood from dialysis machine

Diagnostic Test: Body composition monitoring
Measurement with BCM (Fresenius) machine

Diagnostic Test: lung ultrasound
ultrasound

Active Comparator: Alfacalcidol
Patients will receive Alfacalcidol i.v. 3 times per week after dialysis Dose titration will take plac every 4 weeks in the first 16 weeks Dose adaptation is based on PTH, SerumCa++, SerumPhosphate, T-50-time
Diagnostic Test: cardiac MRI
non contrast heart MRI at baseline and after 1 year of therapy

Diagnostic Test: echocardiography with strain
echocardiography at baseline and after 1 year of therapy

Diagnostic Test: Laboratory tests
drawing blood from dialysis machine

Diagnostic Test: Body composition monitoring
Measurement with BCM (Fresenius) machine

Diagnostic Test: lung ultrasound
ultrasound




Primary Outcome Measures :
  1. Left ventricular mass index [ Time Frame: 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



Secondary Outcome Measures :
  1. Cardiac structure [ Time Frame: one year ]
    Difference in left atrial diameter measured by cMRI (mm)

  2. Cardiac structure [ Time Frame: one year ]
    Change in LVMI progression in either treatment group (%) measured in cMRI

  3. Cardiac structure [ Time Frame: one year ]
    Change in LAD progression in either treatment group (%) measured in cMRI

  4. Cardiac structure [ Time Frame: one year ]
    Difference in cardiac fibrosis (%) measured by cMRI and cardiac strain

  5. Cardiac structure [ Time Frame: one year ]
    Difference in the progression of cardiac fibrosis (%) measured by cMRI and cardiac strain

  6. Cardiac structure [ Time Frame: one year ]
    Differences in cardiac function (ejection fraction - %) measured in cMRI

  7. Cardiac structure [ Time Frame: one year ]
    Differences in wall motion abnormalities measured in cMRI (%)

  8. Laboratory parameters [ Time Frame: one year ]
    Changes in metabolites of the RAAS (pg/ml) using mass spectrometry ("RAAS fingerprint") under either treatment

  9. Laboratory parameters [ Time Frame: one year ]
    Change from baseline serum levels of FGF23 (RU/mL) under either drug

  10. Laboratory parameters [ Time Frame: one year ]
    Change from baseline serum levels of s-klotho (pg/mL) under either drug

  11. Laboratory parameters [ Time Frame: one year ]
    Change from baseline in PTH (ng/l) under either treatment

  12. Laboratory parameters [ Time Frame: one year ]
    Change from baseline in 25-OH-Vit-D (nmol/L) under either treatment

  13. Laboratory parameters [ Time Frame: one year ]
    Change from baseline in 1,25-(OH)2-Vit-D (pg/mL) under either treatment

  14. Laboratory parameters [ Time Frame: one year ]
    Change from baseline in serum phosphate (mmol/l) under either treatment

  15. Laboratory parameters [ Time Frame: one year ]
    Change from baseline in serum calcium (mmol/l) corrected for serum albumin under either treatment

  16. Laboratory parameters [ Time Frame: one year ]
    Changes from baseline in proBNP (pg/ml) in either medication group

  17. Laboratory parameters [ Time Frame: one year ]
    Changes from baseline in pre- and postdialysis TnT (ng/ml) in either medication group

  18. T-50-time measurement [ Time Frame: one year ]
    After completion of the trial two T-50-test will be performed in each patient from existing frozen serum samples (one at baseline and one at the end of 12 months of treatment). The measurement of the T50-time can evaluate an individual's risk for the development of vascular calcification

  19. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of FGF23 in pg/mL from baseline.

  20. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of PTH in ng/L from baseline.

  21. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of calcium corrected for albumin in mg/dL from baseline.

  22. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of s-klotho in pg/mL from baseline.

  23. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of phosphate in mg/dL from baseline.

  24. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of 25-OH-Vitamin-D in nmol/L from baseline

  25. Laboratory parameters [ Time Frame: One year ]
    Longitudinal change in serum levels of 1,25-(OH)2-Vitamin-D in pg/mL from baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 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

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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03182699


Locations
Layout table for location information
Austria
Medical University of Vienna
Vienna, Austria, 1090
Wiener Dialysezentrum
Vienna, Austria, 1220
Sponsors and Collaborators
Rainer Oberbauer
Amgen
Investigators
Layout table for investigator information
Principal Investigator: Rainer Oberbauer, Univ.Prof. Head of the department of Nephrology of the MUVienna
Principal Investigator: Matthias Lorenz, Priv.Doz. Head of the Dialysis center (WDZ)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Rainer Oberbauer, Univ.-Prof. Rainer Oberbauer, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03182699    
Other Study ID Numbers: Etecarhd
First Posted: June 9, 2017    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rainer Oberbauer, Medical University of Vienna:
Secondary Hyperparathyroidism
Hemodialysis
Left Ventricular Hypertrophy
FGF 23
Etelcalcetide
Alfacalcidol
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Hypertrophy, Left Ventricular
Cardiomegaly
Hyperparathyroidism
Hyperparathyroidism, Secondary
Hypertrophy
Urologic Diseases
Renal Insufficiency
Parathyroid Diseases
Endocrine System Diseases
Pathological Conditions, Anatomical
Heart Diseases
Cardiovascular Diseases