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Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial.
JAMA. 2017 01 10; 317(2):156-164.JAMA

Abstract

Importance

Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects.

Objective

To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet.

Design, Setting, and Participants

A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015.

Interventions

Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily.

Main Outcomes and Measures

The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting.

Results

The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%).

Conclusions and Relevance

Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.

Trial Registration

clinicaltrials.gov Identifier: NCT1896232.

Authors+Show Affiliations

Denver Nephrology, Denver, Colorado.University of Rochester, Rochester, New York.Amgen Inc, Thousand Oaks, California.University College London, London, United Kingdom.Amgen Inc, Thousand Oaks, California.Inserm, Université de Picardie, Amiens, France.Klinikum Coburg-GmbH, Coburg, Germany.Amgen Inc, Thousand Oaks, California.St Louis University, St Louis, Missouri.Indiana University, Indianapolis.Duke University, Durham, North Carolina.Hadassah Hebrew University Medical Center, Jerusalem, Israel.Amgen Inc, Thousand Oaks, California.Amgen Inc, Thousand Oaks, California.Stanford University, Stanford, California.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

28097356

Citation

Block, Geoffrey A., et al. "Effect of Etelcalcetide Vs Cinacalcet On Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: a Randomized Clinical Trial." JAMA, vol. 317, no. 2, 2017, pp. 156-164.
Block GA, Bushinsky DA, Cheng S, et al. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017;317(2):156-164.
Block, G. A., Bushinsky, D. A., Cheng, S., Cunningham, J., Dehmel, B., Drueke, T. B., Ketteler, M., Kewalramani, R., Martin, K. J., Moe, S. M., Patel, U. D., Silver, J., Sun, Y., Wang, H., & Chertow, G. M. (2017). Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA, 317(2), 156-164. https://doi.org/10.1001/jama.2016.19468
Block GA, et al. Effect of Etelcalcetide Vs Cinacalcet On Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: a Randomized Clinical Trial. JAMA. 2017 01 10;317(2):156-164. PubMed PMID: 28097356.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. AU - Block,Geoffrey A, AU - Bushinsky,David A, AU - Cheng,Sunfa, AU - Cunningham,John, AU - Dehmel,Bastian, AU - Drueke,Tilman B, AU - Ketteler,Markus, AU - Kewalramani,Reshma, AU - Martin,Kevin J, AU - Moe,Sharon M, AU - Patel,Uptal D, AU - Silver,Justin, AU - Sun,Yan, AU - Wang,Hao, AU - Chertow,Glenn M, PY - 2017/1/19/entrez PY - 2017/1/18/pubmed PY - 2017/2/10/medline SP - 156 EP - 164 JF - JAMA JO - JAMA VL - 317 IS - 2 N2 - Importance: Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. Objective: To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. Design, Setting, and Participants: A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015. Interventions: Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. Main Outcomes and Measures: The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. Results: The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%). Conclusions and Relevance: Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT1896232. SN - 1538-3598 UR - https://wwww.unboundmedicine.com/medline/citation/28097356/Effect_of_Etelcalcetide_vs_Cinacalcet_on_Serum_Parathyroid_Hormone_in_Patients_Receiving_Hemodialysis_With_Secondary_Hyperparathyroidism:_A_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.19468 DB - PRIME DP - Unbound Medicine ER -