Rationale and study design of a randomized controlled trial for development of a treatment strategy for chronic kidney disease\u2013mineral and bone disorder by multilateral mechanism of etelcalcetide hydrochloride (the DUET study)

Abstract

BackgroundSecondary hyperparathyroidism (SHPT) is a common complication in advanced chronic kidney disease (CKD). The aims of this study are to clarify the efficacy of etelcalcetide, a novel-approved intravenous calcimimetic, for evaluating the optimal therapy for etelcalcetide-induced hypocalcemia, and to identify sensitive markers for vascular calcification in patients undergoing maintenance dialysis.MethodsThe Development of treatment strategy for CKD-MBD by mUltilateral mechanism of ETelcalcetide hydrochloride (DUET) study is a 12-week multicenter, open-label, randomized (1:1:1), parallel-group study in SHPT patients undergoing maintenance hemodialysis. A total of 120 patients will be randomly assigned to etelcalcetide + active vitamin D, etelcalcetide + oral calcium preparation, or control (standard therapy) groups. If hypocalcemia is induced by etelcalcetide, active vitamin D and oral calcium preparations will be administered, in addition to the original medications, to patients allocated to etelcalcetide + active vitamin D and etelcalcetide + oral calcium preparation, respectively. The primary endpoint will be to compare the proportion of patients with a 50% reduction in serum intact parathyroid hormone (iPTH) levels after 12 treatment weeks with etelcalcetide relative to baseline values and iPTH levels ≤ 240 pg/mL at the 12-week time point after the trial starts between the intervention group and non-intervention group.ResultsThe background, rationale, and study design of this trial will be also presented. To date, over 100 patients have been enrolled in this trial. The entire study will end in 2020.ConclusionThe DUET trial will provide new evidence regarding the development of a treatment strategy using etelcalcetide for suitable control of iPTH levels and will define the optimal therapy for etelcalcetide-induced hypocalcemia in dialysis patients with SHPT.Trial registrationUMIN-CTR, UMIN-CTR000030392. Registered January 1, 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034259. jRCT, jRCTs041180108. Registered March 11, 2019.