Secondary HyperparathyroidismPhase 4EtECAR-HDNCT03182699
Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients
A Phase 4 study testing cardiac MRI, echocardiography with strain and Laboratory tests in people with Secondary Hyperparathyroidism and Chronic Kidney Disease Requiring Chronic Dialysis, run by Rainer Oberbauer at 2 sites in Austria.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Secondary Hyperparathyroidism, Chronic Kidney Disease Requiring Chronic Dialysis, Left Ventricular Hypertrophy
- What is being tested?
- cardiac MRI, echocardiography with strain and Laboratory tests
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 2 sitesAustria
- Study dates
- 1 Oct 2017to 20 Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Austria2 sites
Medical University of Vienna
Vienna, 1090
Wiener Dialysezentrum
Vienna, 1220
About this study
Official title: Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients: A Randomized Controlled Trial
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).
Read more
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").
Read the detailed description
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
In this trial the investigators will determine the influence of calcimimetic therapy on left ventricular hypertrophy (LVH) in hemodialysis patients with sHPT: They will perform a head-2-head trial testing etelcalcetide vs. alfacalcidol treatment on top of conventional HPT therapy (phosphate binders, calcium supplementation and if necessary vitamin D substitution or cinacalcet) for 12 months. 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) that will be assessed using cardiac magnetic resonance imaging (cMRI) at baseline and after 12 months of treatment. As secondary end points we will measure changes in left atrial diameter (LAD), cardiac fibrosis (using T1 mapping and cardiac strain), wall motion abnormalities and left ventricular function (measured in cMRI and echocardiography), 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.
Specific aim 2
The pathophysiology by which elevated FGF 23 levels can cause cardiac remodeling is still unresolved. The two major hypothesis propose either a direct effect of FGF 23 on the myocardium or a predominantly volume dependent effect caused by FGF 23 and Klotho mediated renal sodium retention:
- Sodium and volume balance in dialysis patients without residual renal function is regulated by ultrafiltration and not by renal sodium handling. In this trial the investigators will perform a stratified randomization procedure to ensure an equal distribution of dialysis patients with residual renal function and those without in both treatment groups.
- Additionally, FGF 23 directly inhibits Angiotensin converting enzyme 2 (ACE 2) as the central enzyme of the antifibrotic alternative renin-angiotensin-aldosterone system (RAAS) and shifting the RAAS toward the pro fibrotic Angiotensin II. To assess suppression of ACE 2 we will measure Ang 1-5 and Ang 1-7 levels by quantitative analysis of the individual metabolites of the RAAS using mass spectrometry ("RAAS fingerprint").
The specific design of this trial will therefore contribute to the fundamental understanding of FGF 23 mediated myocardial remodeling.
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
- Conditions
- Secondary Hyperparathyroidism, Chronic Kidney Disease Requiring Chronic Dialysis, Left Ventricular Hypertrophy
- Being tested
- cardiac MRI, echocardiography with strain, Laboratory tests, Body composition monitoring, lung ultrasound
- Keywords
- Secondary Hyperparathyroidism, Hemodialysis, Left Ventricular Hypertrophy, FGF 23, Etelcalcetide, Alfacalcidol
- Medical subject headings
- Hyperparathyroidism, Secondary, Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cardiac MRIDiagnostic test
non contrast heart MRI at baseline and after 1 year of therapy
echocardiography with strainDiagnostic test
echocardiography at baseline and after 1 year of therapy
Laboratory testsDiagnostic test
drawing blood from dialysis machine
Body composition monitoringDiagnostic test
Measurement with BCM (Fresenius) machine
lung ultrasoundDiagnostic test
ultrasound
| Study group | Role | What they receive |
|---|---|---|
| Etelcalcetide | Experimental | 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 Receives: Diagnostic Test: cardiac MRI; Diagnostic Test: echocardiography with strain; Diagnostic Test: Laboratory tests; Diagnostic Test: Body composition monitoring; Diagnostic Test: lung ultrasound |
| Alfacalcidol | Active comparator | 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 Receives: Diagnostic Test: cardiac MRI; Diagnostic Test: echocardiography with strain; Diagnostic Test: Laboratory tests; Diagnostic Test: Body composition monitoring; Diagnostic Test: lung ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular mass index
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
Measured: one year
Secondary outcomes (25)
Cardiac structure
Difference in left atrial diameter measured by cMRI (mm)
Measured: one year
Cardiac structure
Change in LVMI progression in either treatment group (%) measured in cMRI
Measured: one year
Cardiac structure
Change in LAD progression in either treatment group (%) measured in cMRI
Measured: one year
Cardiac structure
Difference in cardiac fibrosis (%) measured by cMRI and cardiac strain
Measured: one year
Cardiac structure
Difference in the progression of cardiac fibrosis (%) measured by cMRI and cardiac strain
Measured: one year
Cardiac structure
Differences in cardiac function (ejection fraction - %) measured in cMRI
Measured: one year
Cardiac structure
Differences in wall motion abnormalities measured in cMRI (%)
Measured: one year
Laboratory parameters
Changes in metabolites of the RAAS (pg/ml) using mass spectrometry ("RAAS fingerprint") under either treatment
Measured: one year
Laboratory parameters
Change from baseline serum levels of FGF23 (RU/mL) under either drug
Measured: one year
Laboratory parameters
Change from baseline serum levels of s-klotho (pg/mL) under either drug
Measured: one year
Laboratory parameters
Change from baseline in PTH (ng/l) under either treatment
Measured: one year
Laboratory parameters
Change from baseline in 25-OH-Vit-D (nmol/L) under either treatment
Measured: one year
Laboratory parameters
Change from baseline in 1,25-(OH)2-Vit-D (pg/mL) under either treatment
Measured: one year
Laboratory parameters
Change from baseline in serum phosphate (mmol/l) under either treatment
Measured: one year
Laboratory parameters
Change from baseline in serum calcium (mmol/l) corrected for serum albumin under either treatment
Measured: one year
Laboratory parameters
Changes from baseline in proBNP (pg/ml) in either medication group
Measured: one year
Laboratory parameters
Changes from baseline in pre- and postdialysis TnT (ng/ml) in either medication group
Measured: one year
T-50-time measurement
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
Measured: one year
Laboratory parameters
Longitudinal change in serum levels of FGF23 in pg/mL from baseline.
Measured: One year
Laboratory parameters
Longitudinal change in serum levels of PTH in ng/L from baseline.
Measured: One year
Laboratory parameters
Longitudinal change in serum levels of calcium corrected for albumin in mg/dL from baseline.
Measured: One year
Laboratory parameters
Longitudinal change in serum levels of s-klotho in pg/mL from baseline.
Measured: One year
Laboratory parameters
Longitudinal change in serum levels of phosphate in mg/dL from baseline.
Measured: One year
Laboratory parameters
Longitudinal change in serum levels of 25-OH-Vitamin-D in nmol/L from baseline
Measured: One year
Laboratory parameters
Longitudinal change in serum levels of 1,25-(OH)2-Vitamin-D in pg/mL from baseline.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start1 Oct 2017
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Secondary HyperparathyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rainer Oberbauer
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Rainer Oberbauer, Medical University of Vienna
- Investigators
- Rainer Oberbauer, Univ.Prof., Principal investigator, Head of the department of Nephrology of the MUViennaMatthias Lorenz, Priv.Doz., Principal investigator, Head of the Dialysis center (WDZ)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03182699
- Sponsor's protocol ID
- Etecarhd
- Acronym
- EtECAR-HD
- Status last verified
- Jun 2020
- First submitted
- 31 May 2017
- Last updated
- 9 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dorr K, Kammerlander A, Lauriero F, Lorenz M, Marculescu R, Beitzke D. Effect of etelcalcetide versus alfacalcidol on left ventricular function and feature-tracking cardiac magnetic resonance imaging in hemodialysis-a post-hoc analysis of a randomized, controlled trial. J Cardiovasc Magn Reson. 2023 Nov 6;25(1):62. doi: 10.1186/s12968-023-00975-4.
PubMed 37932788Dorr K, Reindl-Schwaighofer R, Lorenz M, Marculescu R, Beitzke D, Hodlmoser S. Etelcalcetide Inhibits the Progression of Left Atrial Volume Index Compared to Alfacalcidol in Hemodialysis Patients. Cardiorenal Med. 2023;13(1):332-341. doi: 10.1159/000533899. Epub 2023 Sep 20.
PubMed 37729887Dorr K, Hodlmoser S, Kammer M, Reindl-Schwaighofer R, Lorenz M, Reiskopf B, Jagoditsch R, Marculescu R, Oberbauer R. Bone Specific Alkaline Phosphatase and Serum Calcification Propensity Are Not Influenced by Etelcalcetide vs. Alfacalcidol Treatment, and Only Bone Specific Alkaline Phosphatase Is Correlated With Fibroblast Growth Factor 23: Sub-Analysis Results of the ETACAR-HD Study. Front Med (Lausanne). 2022 Jul 6;9:948177. doi: 10.3389/fmed.2022.948177. eCollection 2022.
PubMed 35872799Dorr K, Kammer M, Reindl-Schwaighofer R, Lorenz M, Marculescu R, Poglitsch M, Beitzke D, Oberbauer R. The Effect of FGF23 on Cardiac Hypertrophy Is Not Mediated by Systemic Renin-Angiotensin- Aldosterone System in Hemodialysis. Front Med (Lausanne). 2022 Apr 26;9:878730. doi: 10.3389/fmed.2022.878730. eCollection 2022.
PubMed 35559350Dorr K, Kammer M, Reindl-Schwaighofer R, Lorenz M, Prikoszovich T, Marculescu R, Beitzke D, Wielandner A, Erben RG, Oberbauer R. Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis. Circ Res. 2021 May 28;128(11):1616-1625. doi: 10.1161/CIRCRESAHA.120.318556. Epub 2021 Apr 7.
PubMed 33825489Dorr K, Kammer M, Reindl-Schwaighofer R, Lorenz M, Loewe C, Marculescu R, Erben R, Oberbauer R. Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD). Trials. 2019 Oct 24;20(1):601. doi: 10.1186/s13063-019-3707-7.
PubMed 31651370
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03182699
- Acronym / sponsor ID
- EtECAR-HD / Etecarhd
- Conditions
- Secondary Hyperparathyroidism, Chronic Kidney Disease Requiring Chronic Dialysis, Left Ventricular Hypertrophy
- Keywords
- Secondary Hyperparathyroidism, Hemodialysis, Left Ventricular Hypertrophy, FGF 23, Etelcalcetide, Alfacalcidol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Rainer OberbauerUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 9 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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").
Detailed description
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
In this trial the investigators will determine the influence of calcimimetic therapy on left ventricular hypertrophy (LVH) in hemodialysis patients with sHPT: They will perform a head-2-head trial testing etelcalcetide vs. alfacalcidol treatment on top of conventional HPT therapy (phosphate binders, calcium supplementation and if necessary vitamin D substitution or cinacalcet) for 12 months. 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) that will be assessed using cardiac magnetic resonance imaging (cMRI) at baseline and after 12 months of treatment. As secondary end points we will measure changes in left atrial diameter (LAD), cardiac fibrosis (using T1 mapping and cardiac strain), wall motion abnormalities and left ventricular function (measured in cMRI and echocardiography), 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.
Specific aim 2
The pathophysiology by which elevated FGF 23 levels can cause cardiac remodeling is still unresolved. The two major hypothesis propose either a direct effect of FGF 23 on the myocardium or a predominantly volume dependent effect caused by FGF 23 and Klotho mediated renal sodium retention:
- Sodium and volume balance in dialysis patients without residual renal function is regulated by ultrafiltration and not by renal sodium handling. In this trial the investigators will perform a stratified randomization procedure to ensure an equal distribution of dialysis patients with residual renal function and those without in both treatment groups.
- Additionally, FGF 23 directly inhibits Angiotensin converting enzyme 2 (ACE 2) as the central enzyme of the antifibrotic alternative renin-angiotensin-aldosterone system (RAAS) and shifting the RAAS toward the pro fibrotic Angiotensin II. To assess suppression of ACE 2 we will measure Ang 1-5 and Ang 1-7 levels by quantitative analysis of the individual metabolites of the RAAS using mass spectrometry ("RAAS fingerprint").
The specific design of this trial will therefore contribute to the fundamental understanding of FGF 23 mediated myocardial remodeling.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etelcalcetide | Experimental | Diagnostic Test: cardiac MRI, Diagnostic Test: echocardiography with strain, Diagnostic Test: Laboratory tests, Diagnostic Test: Body composition monitoring, Diagnostic Test: lung ultrasoundPatients 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 |
| Alfacalcidol | Active comparator | Diagnostic Test: cardiac MRI, Diagnostic Test: echocardiography with strain, Diagnostic Test: Laboratory tests, Diagnostic Test: Body composition monitoring, Diagnostic Test: lung ultrasoundPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥ 18 years of age
- Treatment with maintenance hemodialysis 3 times a week for ≥ 3 months and ≤3 years
- sHPT defined by
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cardiac MRInon contrast heart MRI at baseline and after 1 year of therapy | Diagnostic test | Alfacalcidol, Etelcalcetide |
| echocardiography with strainechocardiography at baseline and after 1 year of therapy | Diagnostic test | Alfacalcidol, Etelcalcetide |
| Laboratory testsdrawing blood from dialysis machine | Diagnostic test | Alfacalcidol, Etelcalcetide |
| Body composition monitoringMeasurement with BCM (Fresenius) machine | Diagnostic test | Alfacalcidol, Etelcalcetide |
| lung ultrasoundultrasound | Diagnostic test | Alfacalcidol, Etelcalcetide |
Primary outcome
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
25 secondary outcomes
Cardiac structure
Time frame: one year
Cardiac structure
Time frame: one year
Cardiac structure
Time frame: one year
Cardiac structure
Time frame: one year
Cardiac structure
Time frame: one year
Cardiac structure
Time frame: one year
Cardiac structure
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
Laboratory parameters
Time frame: one year
T-50-time measurement
Time frame: one year
Laboratory parameters
Time frame: One year
Laboratory parameters
Time frame: One year
Laboratory parameters
Time frame: One year
Laboratory parameters
Time frame: One year
Laboratory parameters
Time frame: One year
Laboratory parameters
Time frame: One year
Laboratory parameters
Time frame: One year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Derived from this study: PubMed 37932788Dorr K, Kammerlander A, Lauriero F, Lorenz M, Marculescu R, Beitzke D. Effect of etelcalcetide versus alfacalcidol on left ventricular function and feature-tracking cardiac magnetic resonance imaging in hemodialysis-a post-hoc analysis of a randomized, controlled trial. J Cardiovasc Magn Reson. 2023 Nov 6;25(1):62. doi: 10.1186/s12968-023-00975-4.
- Derived from this study: PubMed 37729887Dorr K, Reindl-Schwaighofer R, Lorenz M, Marculescu R, Beitzke D, Hodlmoser S. Etelcalcetide Inhibits the Progression of Left Atrial Volume Index Compared to Alfacalcidol in Hemodialysis Patients. Cardiorenal Med. 2023;13(1):332-341. doi: 10.1159/000533899. Epub 2023 Sep 20.
- Derived from this study: PubMed 35872799Dorr K, Hodlmoser S, Kammer M, Reindl-Schwaighofer R, Lorenz M, Reiskopf B, Jagoditsch R, Marculescu R, Oberbauer R. Bone Specific Alkaline Phosphatase and Serum Calcification Propensity Are Not Influenced by Etelcalcetide vs. Alfacalcidol Treatment, and Only Bone Specific Alkaline Phosphatase Is Correlated With Fibroblast Growth Factor 23: Sub-Analysis Results of the ETACAR-HD Study. Front Med (Lausanne). 2022 Jul 6;9:948177. doi: 10.3389/fmed.2022.948177. eCollection 2022.
- Derived from this study: PubMed 35559350Dorr K, Kammer M, Reindl-Schwaighofer R, Lorenz M, Marculescu R, Poglitsch M, Beitzke D, Oberbauer R. The Effect of FGF23 on Cardiac Hypertrophy Is Not Mediated by Systemic Renin-Angiotensin- Aldosterone System in Hemodialysis. Front Med (Lausanne). 2022 Apr 26;9:878730. doi: 10.3389/fmed.2022.878730. eCollection 2022.
- Derived from this study: PubMed 33825489Dorr K, Kammer M, Reindl-Schwaighofer R, Lorenz M, Prikoszovich T, Marculescu R, Beitzke D, Wielandner A, Erben RG, Oberbauer R. Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis. Circ Res. 2021 May 28;128(11):1616-1625. doi: 10.1161/CIRCRESAHA.120.318556. Epub 2021 Apr 7.
- Derived from this study: PubMed 31651370Dorr K, Kammer M, Reindl-Schwaighofer R, Lorenz M, Loewe C, Marculescu R, Erben R, Oberbauer R. Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD). Trials. 2019 Oct 24;20(1):601. doi: 10.1186/s13063-019-3707-7.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer Oberbauer, Univ.Prof. principal investigator
Head of the department of Nephrology of the MUVienna
Matthias Lorenz, Priv.Doz. principal investigator
Head of the Dialysis center (WDZ)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cardiac MRI, echocardiography with strain and Laboratory tests in people with Secondary Hyperparathyroidism and Chronic Kidney Disease Requiring Chronic Dialysis, run by Rainer Oberbauer at 2 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular mass index (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03182699, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.