Effect of Etelcalcetide on Cardiac Hypertrophy in Hemodialysis Patients

NCT03182699 | Completed Phase 4 DMC

• 1 other identifier: Etecarhd
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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").

Conditions

Secondary Hyperparathyroidism; Chronic Kidney Disease Requiring Chronic Dialysis; Left Ventricular Hypertrophy

Keywords

Secondary Hyperparathyroidism; Hemodialysis; Left Ventricular Hypertrophy; FGF 23; Etelcalcetide; Alfacalcidol

Outcome Measures

Primary Outcomes (1)

• 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

  one year

Secondary Outcomes (25)

• Cardiac structure

  one year

• Cardiac structure

  one year

• Cardiac structure

  one year

• Cardiac structure

  one year

• Cardiac structure

  one year

Study Arms (2)

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

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

Diagnostic Test: cardiac MRI; Diagnostic Test: echocardiography with strain; Diagnostic Test: Laboratory tests; Diagnostic Test: Body composition monitoring; Diagnostic Test: lung ultrasound

Interventions

cardiac MRI DIAGNOSTIC_TEST

non contrast heart MRI at baseline and after 1 year of therapy

Alfacalcidol; Etelcalcetide

echocardiography with strain DIAGNOSTIC_TEST

echocardiography at baseline and after 1 year of therapy

Alfacalcidol; Etelcalcetide

Laboratory tests DIAGNOSTIC_TEST

drawing blood from dialysis machine

Alfacalcidol; Etelcalcetide

Body composition monitoring DIAGNOSTIC_TEST

Measurement with BCM (Fresenius) machine

Alfacalcidol; Etelcalcetide

lung ultrasound DIAGNOSTIC_TEST

ultrasound

Alfacalcidol; Etelcalcetide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rainer Oberbauer: lead
• Amgen: collaborator

Study Sites (2)

Medical University of Vienna

Vienna, 1090, Austria

Location

Wiener Dialysezentrum

Vienna, 1220, Austria

Location

Related Publications (6)

• 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.

  PMID: 37932788 DERIVED

• Dorr 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.

  PMID: 37729887 DERIVED

• Dorr 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.

  PMID: 35872799 DERIVED

• Dorr 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.

  PMID: 35559350 DERIVED

• Dorr 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.

  PMID: 33825489 DERIVED

• Dorr 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.

  PMID: 31651370 DERIVED

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Hypertrophy, Left Ventricular

Interventions

Echocardiography; Clinical Laboratory Techniques

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Investigative Techniques

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Radiologist investigating the cMRI and physician performing the echocardiography will be blinded. Patients will also be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Univ.-Prof. Rainer Oberbauer

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 9, 2017
• Study Start: October 1, 2017
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: June 9, 2020

Record last verified: 2020-06

Locations

AU (2)