Comparative Effects Of Etelcalcetide And Maxacalcitol On Serum Calcification Propensity In Secondary Hyperparathyroidism A Randomized Clinical Trial

Background and objectives Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T-50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. Wetested a hypothesis that a calcimimetic agent etelcalcetide ismore effective in increasing T-50 value than a vitamin D receptor activator maxacalcitol. Design, setting, participants,& measurementsArandomized, multicenter, open-label, blinded end point trialwith active controlwas conductedinpatientswithsecondary hyperparathyroidismundergoing hemodialysis inJapan. Patients were randomly assigned to receive intravenous etelcalcetide 5mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 mg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T-50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. Results In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n5167; control, n5159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T-50 value was changed from 116 minutes (interquartile range, 90-151) to 131 minutes (interquartile range, 102-176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98-174) to 166 minutes (interquartile range, 127-218) in the etelcalcetide group. The increase in T-50 value was significantly greater in the etelcalcetide group (difference in change, 20minutes; 95% confidence interval, 7 to 34minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. Conclusions Etelcalcetide was more effective in increasing T-50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs.