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Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD).

ABSTRACT: BACKGROUND:Fibroblast growth factor 23 (FGF23) is associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease, and calcimimetic therapy reduces plasma concentrations of FGF23. It remains unknown whether treatment with the calcimimetic etelcalcetide (ETL) reduces LVH in patients on hemodialysis. METHODS/DESIGN:This single-blinded randomized trial of 12 months duration will test the effects of ETL compared with alfacalcidol on LVH and cardiac fibrosis in maintenance hemodialysis patients with secondary hyperparathyroidism. Both treatment regimens will be titrated to equally suppress secondary hyperparathyroidism while alfacalcidol treatment causes an increase and ETL a decrease in FGF23, respectively. Patients treated thrice weekly with hemodialysis for ??3?months and???3?years with parathyroid hormone levels ??300?pg/ml and LVH will be enrolled in the study. The primary study endpoint is change from baseline to 12?months in left ventricular mass index (LVMI; g/m2) measured by cardiac magnetic resonance imaging. Sample size calculations showed that 62 randomized patients will be necessary to detect a difference in LVMI of at least 20?g/m2 between the two groups at 12?months. Due to the strong association of volume overload and LVH, randomization will be stratified by residual kidney function, and regular body composition monitoring will be performed to control the volume status of patients. Study medication will be administered intravenously by the dialysis nurses after every hemodialysis session, thus omitting adherence issues. Secondary study endpoints are cardiac parameters measured by echocardiography, biomarker concentrations of bone metabolism (FGF23, vitamin D, parathyroid hormone, calcium, phosphate, s-Klotho), cardiac markers (pro-brain natriuretic peptide, pre- and postdialysis troponin T) and metabolites of the renin-angiotensin-aldosterone cascade (angiotensin I (Ang I), Ang II, Ang-(1-7), Ang-(1-5), Ang-(1-9), and aldosterone). DISCUSSION:The causal inference and pathophysiology of LVH regression by FGF23 reduction using calcimimetic treatment has not yet been shown. This intervention study has the potential to discover a new strategy for the treatment of cardiac hypertrophy and fibrosis in patients on maintenance hemodialysis. It might be speculated that successful treatment of cardiac morphology will also reduce the risk of cardiac death in this population. TRIAL REGISTRATION:European Clinical Trials Database, EudraCT number 2017-000222-35; ClinicalTrials.gov, NCT03182699 . Registered on.

SUBMITTER: Dorr K

PROVIDER: S-EPMC6813957 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD).

Dörr Katharina K Kammer Michael M Reindl-Schwaighofer Roman R Lorenz Matthias M Loewe Christian C Marculescu Rodrig R Erben Reinhold R Oberbauer Rainer R

Trials 20191024 1

<h4>Background</h4>Fibroblast growth factor 23 (FGF23) is associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease, and calcimimetic therapy reduces plasma concentrations of FGF23. It remains unknown whether treatment with the calcimimetic etelcalcetide (ETL) reduces LVH in patients on hemodialysis.<h4>Methods/design</h4>This single-blinded randomized trial of 12 months duration will test the effects of ETL compared with alfacalcidol on LVH and cardiac fibrosis ...[more]

PMID: 31651370

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Project description:BackgroundPatients receiving in-center hemodialysis experience disproportionate morbidity and incur high healthcare-related costs. Much of this cost stems from potentially avoidable hospitalizations. Peer mentorship has been used effectively to improve outcomes for patients with complex chronic diseases. We propose testing the efficacy of peer mentorship on hospitalization rates among patients receiving hemodialysis.MethodsThis is a multicenter parallel group randomized controlled pragmatic trial of patients treated at hemodialysis facilities in Bronx, NY and Nashville, TN. The study has two phases. Phase 1 will enroll and train 16 hemodialysis patients (10 in Bronx, NY and 6 in Nashville TN) to be mentors using a program focused on enhancing self-efficacy, dialysis self-management and autonomy-supportive communication skills. Phase 2 will enroll 200 high risk adults receiving hemodialysis (140 in Bronx, NY and 60 in Nashville, TN), half of whom will be randomized to intervention and half to usual care. Intervention participants are assigned to weekly telephone calls with trained mentors (see Phase 1) for a 3-month period. The primary outcome of Phase 1 will be engagement of mentors with training and change in knowledge scores and autonomy skills from pre- to post-training. The primary outcome of Phase 2 will be the composite count of ED visits and hospitalizations at the end of study follow-up in patient participants assigned to intervention as compared to those assigned to usual care. Secondary outcomes for Phase 2 include the change over the trial period in validated survey scores measuring perception of social support and self-efficacy, and dialysis adherence metrics, among intervention participants as compared to usual care participants.DiscussionThe PEER-HD study will test the feasibility and efficacy of a pragmatic peer-mentorship program designed for patients receiving hemodialysis on ED visit and hospitalization rates. If effective, peer-mentorship holds promise as a scalable patient-centered intervention to decrease hospital resource utilization, and by extension morbidity and cost, for patients receiving maintenance in-center hemodialysis.Trial registrationClinicaltrials.gov identifier: NCT03595748 ; 7/23/2018.Trial sponsorNational Institutes of Diabetes, Digestive and Kidney Disease (NIDDK) 5R18DK118471.FundingFunding for this study was provided by the National Institutes of Diabetes, Digestive and Kidney Disease: R18DK118471.Study statusThis is an ongoing study and not complete. We are still collecting data for observational follow-up on participants.Related articlesNo related articles for this study have been submitted to any journal. The study sponsor and funders had no role in the design, analysis or interpretation of this data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Project description:Background and objectivesCardiovascular disease is the most common cause of death in patients on hemodialysis (HD). HD-associated cardiomyopathy is appreciated to be driven by exposure to recurrent and cumulative ischemic insults resulting from hemodynamic instability of conventionally performed intermittent HD treatment itself. Cooled dialysate reduces HD-induced recurrent ischemic injury, but whether this confers long-term protection of the heart in terms of cardiac structure and function is not known.Design, setting, participants, & measurementsBetween September 2009 and January 2013, 73 incident HD patients were randomly assigned to a dialysate temperature of 37°C (control) or individualized cooling at 0.5°C below body temperature (intervention) for 12 months. Cardiac structure, function, and aortic distensibility were assessed by cardiac magnetic resonance imaging. Mean between-group difference in delivered dialysate temperature was 1.2°C±0.3°C. Treatment effects were determined by the interaction of treatment group with time in linear mixed models.ResultsThere was no between-group difference in the primary outcome of left ventricular ejection fraction (1.5%; 95% confidence interval, -4.3% to 7.3%). However, left ventricular function assessed by peak systolic strain was preserved by the intervention (-3.3%; 95% confidence interval, -6.5% to -0.2%) as was diastolic function (measured as peak diastolic strain rate, 0.18 s(-1); 95% confidence interval, 0.02 to 0.34 s(-1)). Reduction of left ventricular dilation was demonstrated by significant reduction in left ventricular end-diastolic volume (-23.8 ml; 95% confidence interval, -44.7 to -2.9 ml). The intervention was associated with reduced left ventricular mass (-15.6 g; 95% confidence interval, -29.4 to -1.9 g). Aortic distensibility was preserved in the intervention group (1.8 mmHg(-1)×10(-3); 95% confidence interval, 0.1 to 3.6 mmHg(-1)×10(-3)). There were no intervention-related withdrawals or adverse events.ConclusionsIn patients new to HD, individualized cooled dialysate did not alter the primary outcome but was well tolerated and slowed the progression of HD-associated cardiomyopathy. Because cooler dialysate is universally applicable at no cost, the intervention warrants wider adoption or confirmation of these findings in a larger trial.

Dataset Information

Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD).

Publications

Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD).

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