Dataset Information

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial.

ABSTRACT:

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 T₅₀ value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T₅₀ value than a vitamin D receptor activator maxacalcitol.

Design, setting, participants, & measurements

A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T₅₀ 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, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T₅₀ 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 T₅₀ value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; 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 T₅₀ value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs.

Clinical trial registry name and registration number

VICTORY; UMIN000030636 and jRCTs051180156.

SUBMITTER: Shoji T

PROVIDER: S-EPMC8092049 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial.

Shoji Tetsuo T Nakatani Shinya S Kabata Daijiro D Mori Katsuhito K Shintani Ayumi A Yoshida Hisako H Takahashi Kanae K Ota Keiko K Fujii Hisako H Ueda Shinichiro S Nishi Shinichi S Nakatani Tatsuya T Yoshiyama Minoru M Goto Kiyoshi K Hamada Takayoshi T Imanishi Masahito M Ishimura Eiji E Kagitani Sosuke S Kato Yoshikazu Y Kumeda Yasuro Y Maekawa Kiyoshi K Matsumura Takayasu T Nagayama Harumi H Obi Yasue Y Ohno Yoshiteru Y Sai Yoshinori Y Sakurai Mayumi M Sasaki Satoshi S Shidara Kaori K Shoji Shigeichi S Tsujimoto Yoshihiro Y Yamakawa Kenjiro K Yasuda Hideaki H Yodoi Shozo S Inaba Masaaki M Emoto Masanori M

Clinical journal of the American Society of Nephrology : CJASN 20210308 4

<h4>Background and objectives</h4>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<sub>50</sub> value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T<sub>50</sub> value than a vitamin D receptor a ...[more]

PMID: 33685864

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Project description:IntroductionCalcimimetics improve parameters of secondary hyperparathyroidism (sHPT) but are mostly initiated when patients have severe disease, potentially limiting effectiveness. We evaluated the effects of etelcalcetide on lowering intact parathyroid hormone, calcium, and phosphate at different disease severity levels.MethodsThis analysis examined data from 2 parallel, phase 3, randomized, placebo-controlled, 26-week trials conducted in 1023 adult (≥18 years old) patients with sHPT on maintenance hemodialysis. Etelcalcetide effects by baseline intact parathyroid hormone stratum (<600, 600-1000, and >1000 ng/l) on mean percentage change in intact parathyroid hormone; changes in calcium and phosphate; and achieving serum intact parathyroid hormone ≤300 ng/l, phosphate <1.78 mmol/l, and both combined, were assessed.ResultsEtelcalcetide reduced serum intact parathyroid hormone by a similar percentage across baseline strata. A similar proportion achieved >30% intact parathyroid hormone reduction across strata for the etelcalcetide arms. Parathyroid hormone increased modestly in each placebo-group stratum, most prominently in the lowest stratum. Serum calcium and phosphate concentrations decreased across strata in etelcalcetide-treated patients, with the most pronounced reductions in patients with highest baseline parathyroid hormone. However, the proportion of patients achieving parathyroid hormone, phosphate, and both targets was highest in the lowest baseline parathyroid hormone stratum, where etelcalcetide dose requirements were lowest. Etelcalcetide dose requirement was lowest among patients in the lowest intact parathyroid hormone stratum.ConclusionEtelcalcetide effectively lowered serum intact parathyroid hormone, calcium, and phosphate, irrespective of the severity of secondary hyperparathyroidism. The ability to achieve target goals was greatest, and dose requirement smallest, when etelcalcetide was initiated among patients with the lowest level of disease severity.

Project description:BackgroundCalcimimetics have been shown to be effective and safe therapies for the treatment of secondary hyperparathyroidism (sHPT), a serious complication of disordered mineral metabolism associated with dialysis-dependent chronic kidney disease. Etelcalcetide, a recently approved intravenous calcimimetic, reduces serum parathyroid hormone (PTH), calcium, phosphorus, and fibroblast growth factor-23 concentrations. Here we report the first integrated safety profile of etelcalcetide using pooled data from five pivotal clinical trials.MethodsThis analysis included data from patients receiving hemodialysis with moderate to severe sHPT enrolled in two randomized, placebo-controlled trials; a randomized active-controlled (with cinacalcet) trial; and two single-arm, open-label extension trials. Patients initially received etelcalcetide intravenously 5 mg three times weekly (TIW) after hemodialysis; with potential dose increases of 2.5 or 5 mg at 4-week intervals to a maximum dose of 15 mg TIW, depending on serum PTH and calcium levels. The nature, frequency, and severity of treatment-emergent adverse events (AEs) and changes in laboratory parameters were assessed.ResultsOverall, we evaluated 1023 patients from the placebo-controlled trials, 683 from the active-controlled trial, and 1299 from open-label extensions. The frequency and nature of common treatment-emergent AEs reported for the etelcalcetide arm were consistent among the placebo-controlled and active-controlled trials. The most common AEs were those related to mineral metabolism (decreased blood calcium, hypophosphatemia, muscle spasms) or gastrointestinal abnormalities (diarrhea, nausea, vomiting). Hypocalcemia leading to discontinuation of either calcimimetic was experienced in ≤ 1% of patients.ConclusionsThis integrated safety assessment of etelcalcetide across placebo- and active-controlled trials showed an overall favorable risk/benefit profile, with safety similar to that of cinacalcet. Consistent with its mechanism of action, the most important risks associated with etelcalcetide were serum calcium reductions and hypocalcemia-related AEs; no new safety findings were identified in the pooled long-term extension trials.

Dataset Information

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Clinical trial registry name and registration number

Publications

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial.

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