Combining etelcalcetide with vitamin D therapy may be a safer approach to correcting calcimimetic-induced hypocalcemia than combining etelcalcetide with calcium, according to Japanese investigators.
In the 12-week open-label DUET trial (Development of treatment strategy for Chronic kidney disease-mineral and bone disorder by mUltilateral mechanism of ETelcalcetide hydrochloride), researchers randomly assigned 124 patients receiving maintenance hemodialysis with intact parathyroid hormone (iPTH) levels of 240 pg/mL or more and corrected serum calcium levels of 8.4 mg/dL or more into 3 groups: Group E+D received intravenous etelcalcetide (starting dose 5 mg) and additional active vitamin D if hypocalcemia developed. Group E+Ca received etelcalcetide and additional oral precipitated calcium carbonate if hypocalcemia developed. A control group received standard therapy using vitamin D and precipitated calcium carbonate alone.
Over 12 weeks, 74.0% of all patients treated with etelcalcetide and 19.5% of control patients achieved the primary endpoint of a more than 50% reduction in iPTH to within a target range of 60 to 240 pg/mL, Sawako Kato, MD, PhD, of Nagoya University Graduate School of Medicine in Aichi, Japan, and colleagues reported in Kidney International Reports. Japan has a stricter iPTH target range than the United States and Europe because Japanese patients tend to have naturally lower levels of the hormone, according to the investigators. A significantly greater proportion of patients in group E+D achieved the primary endpoint compared with those in group E+Ca and group C (90.0 % vs 56.8% vs 19.5%, respectively). Etelcalcetide treatment was significantly associated with 13.4-fold increased odds of reaching the primary endpoint. A limitation of the study is that a third of patients started treatment with in-range iPTH at baseline.
Half of etelcalcetide-treated patients experienced iPTH oversuppression, however. Additionally, in 29.6% and 42.5% of visits, group E+D and group E+Ca, respectively, showed hypocalcemia (corrected calcium of less than 8.3 mg/dL), compared with 2.4% of visits for the control group.
Active vitamin D had a 6-fold greater likelihood of correcting calcimimetic-induced hypocalcemia than oral calcium. Conversely, oral calcium was superior in suppressing serum phosphate and calcium-phosphate product.
“Since active vitamin D was useful in correcting hypocalcemia while oral calcium preparation was superior in suppressing hyperphosphatemia, the combination of active vitamin D, calcium-free phosphate binder, and an oral calcium preparation may be necessary for management of hypocalcemia induced by calcimimetics,” Dr Kato’s team stated.
Disclosure: This clinical trial was supported by Ono Pharmaceutical. Please see the original reference for a full list of authors’ disclosures.
Itano Y, Kato S, Tsuboi M, et al. A prospective, randomized clinical trial of etelcalcetide in patients receiving hemodialysis with secondary hyperthyroidism (The DUET trial). Kidney Intl Reps. doi:10.1016/j.ekir.2020.09.010