Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: Two randomized clinical trials

JAMA - Journal of the American Medical Association

Volumn 317, Issue 2, 2017, Pages 146-155

  Block, Geoffrey A ^a   Bushinsky, David A ^b   Cunningham, John ^c   Drueke, Tilman B ^d   Ketteler, Markus ^e   Kewalramani, Reshma ^f   Martin, Kevin J ^g   Mix, T Christian ^f   Moe, Sharon M ^h   Patel, Uptal D ⁱ   Silver, Justin ^j   Spiegel, David M ^f   Sterling, Lulu ^f   Walsh, Liron ^f   Chertow, Glenn M ^k,l  

^a Denver Nephrology   (United States)

^b UNIVERSITY OF ROCHESTER   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITÉ DE PICARDIE JULES VERNE   (France)

^e KLINIKUM COBURG   (Germany)

^f AMGEN INC   (United States)

^g SAINT LOUIS UNIVERSITY   (United States)

^h INDIANA UNIVERSITY   (United States)

ⁱ DUKE UNIVERSITY   (United States)

^j HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^k STANFORD UNIVERSITY   (United States)

^l STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ETELCALCETIDE; PARATHYROID HORMONE; AMG-416; CALCIMIMETIC AGENT; CALCIUM; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 23; PEPTIDE;

ARTICLE; AUSTRALIA; BACKACHE; CALCIUM BLOOD LEVEL; CANADA; CEREBROVASCULAR ACCIDENT; DIARRHEA; DISEASE SEVERITY; DRUG EFFECT; DRUG EFFICACY; DRUG FATALITY; EUROPE; HEADACHE; HEART INFARCTION; HEMODIALYSIS PATIENT; HUMAN; HYPERTENSION; HYPOCALCEMIA; HYPOTENSION; ISRAEL; LIMB PAIN; MULTICENTER STUDY (TOPIC); MUSCLE SPASM; NAUSEA; PARALLEL DESIGN; PARATHYROID HORMONE BLOOD LEVEL; PARESTHESIA; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RUSSIAN FEDERATION; SECONDARY HYPERPARATHYROIDISM; SEIZURE; SIDE EFFECT; UNITED STATES; UPPER RESPIRATORY TRACT INFECTION; VOMITING; BLOOD; CHRONIC KIDNEY FAILURE; CLINICAL TRIAL; COMPLICATION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; FEMALE; HEMODIALYSIS; HYPERPARATHYROIDISM, SECONDARY; INTRAVENOUS DRUG ADMINISTRATION; MALE; MIDDLE AGED; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; PLACEBO EFFECT; PROCEDURES; RANDOMIZED CONTROLLED TRIAL; TIME FACTOR;

CALCIMIMETIC AGENTS; CALCIUM; DOUBLE-BLIND METHOD; FEMALE; FIBROBLAST GROWTH FACTORS; HUMANS; HYPERPARATHYROIDISM, SECONDARY; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; PARATHYROID HORMONE; PEPTIDES; PLACEBO EFFECT; RENAL DIALYSIS; RENAL INSUFFICIENCY, CHRONIC; TIME FACTORS;

EID: 85010612346     PISSN: 00987484     EISSN: 15383598     Source Type: Journal    
DOI: 10.1001/jama.2016.19456     Document Type: Article

References (29)

1. Kidney Disease Improving Global Outcomes CKD-MBDWorkgroup. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 2009;76 (suppl 113):1-140.
2. Tentori F, Wang M, Bieber BA, et al. Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: The DOPPS study. Clin J AmSoc Nephrol. 2015;10(1):98- 109.
3. Martin KJ, Bell G, Pickthorn K, et al. Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. Nephrol Dial Transplant. 2014;29(2): 385-392.
4. Chen P, Melhem M, Xiao J, Kuchimanchi M, Perez Ruixo JJ. Population pharmacokinetics analysis of AMG 416, an allosteric activator of the calcium-sensing receptor, in subjects with secondary hyperparathyroidism receiving hemodialysis. J Clin Pharmacol. 2015;55(6):620-628.
5. Block GA, Martin KJ, Bushinsky DA, et al. Results of a 12-week dose titration study evaluating the safety and efficacy of velcalcitide, a novel peptide agonist of the calcium sensing receptor for the treatment of secondary hyperparathyroidism in hemodialysis subjects. Abstract presented at: American Society of Nephrology Annual Meeting; November 5-10, 2013; Atlanta, GA.
6. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J AmSoc Nephrol. 2001;12 (10):2131-2138.
7. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J AmSoc Nephrol. 2004;15(8):2208- 2218.
8. Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006;70(4):771-780.
9. Danese MD, Kim J, Doan QV, Dylan M, Griffiths R, Chertow GM. PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis. Am J Kidney Dis. 2006;47(1):149-156.
10. Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature. 1993;366(6455):575-580.
11. Ketteler M, Martin KJ, Wolf M, et al. Paricalcitol vs cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: Results of the IMPACT SHPT study. Nephrol Dial Transplant. 2012; 27(8):3270-3278.
12. Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int. 2005;68(4):1793- 1800.
13. Chertow GM, Block GA, Correa-Rotter R, et al; EVOLVE Trial Investigators. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482-2494.
14. Moe SM, Abdalla S, Chertow GM, et al; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial Investigators. Effects of cinacalcet on fracture events in patients receiving hemodialysis: The EVOLVE trial. J Am Soc Nephrol. 2015;26(6):1466-1475.
15. Parfrey PS, Chertow GM, Block GA, et al. The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: The EVOLVE trial. J Clin Endocrinol Metab. 2013;98(12):4834-4844.
16. Floege J, Kubo Y, Floege A, Chertow GM, Parfrey PS. The effect of cinacalcet on calcific uremic arteriolopathy events in patients receiving hemodialysis: The EVOLVE trial. Clin J AmSoc Nephrol. 2015;10(5):800-807.
17. Ishani A, Liu J, Wetmore JB, et al. Clinical outcomes after parathyroidectomy in a nationwide cohort of patients on hemodialysis. Clin J Am Soc Nephrol. 2015;10(1):90-97.
18. Streja E, Lau WL, Goldstein L, et al. Hyperphosphatemia is a combined function of high serum PTH and high dietary protein intake in dialysis patients. Kidney Int Suppl (2011). 2013;3(5): 462-468.
19. Isakova T, Wahl P, Vargas GS, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79(12):1370-1378.
20. Rebholz CM, Grams ME, Coresh J, et al; Chronic Kidney Disease Biomarkers Consortium. Serum fibroblast growth factor-23 is associated with incident kidney disease. J AmSoc Nephrol. 2015;26 (1):192-200.
21. Scialla JJ, Astor BC, Isakova T, Xie H, Appel LJ, Wolf M. Mineral metabolites and CKD progression in African Americans. J AmSoc Nephrol. 2013;24(1): 125-135.
22. Scialla JJ, Xie H, Rahman M, et al; Chronic Renal Insufficiency Cohort Study Investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J AmSoc Nephrol. 2014;25(2):349-360.
23. Isakova T, Xie H, YangW, et al; Chronic Renal Insufficiency Cohort Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011;305(23):2432-2439.
24. Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121(11):4393-4408.
25. Rodriguez-Ortiz ME, Lopez I, Muñoz-Castañeda JR, et al. Calcium deficiency reduces circulating levels of FGF23. J AmSoc Nephrol. 2012;23(7):1190- 1197.
26. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: Physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75: 503-533.
27. Meir T, Durlacher K, Pan Z, et al. Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription. Kidney Int. 2014;86(6):1106-1115.
28. Moe SM, Chertow GM, Parfrey PS, et al; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial Investigators. Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial. Circulation. 2015;132(1): 27-39.
29. Raggi P, Chertow GM, Torres PU, et al; ADVANCE Study Group. The ADVANCE study: A randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011;26(4):1327-1339.