Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study

• Published in: Nephrology, dialysis, transplantation Vol. 27; no. 8; pp. 3270 - 3278
• Main Authors: Ketteler, M., Martin, K. J., Wolf, M., Amdahl, M., Cozzolino, M., Goldsmith, D., Sharma, A., Marx, S., Khan, S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2012
• Subjects: Administration, Intravenous; Administration, Oral; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone Density; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Calcium - blood; Cinacalcet Hydrochloride; Clinical Science; Drug Therapy, Combination; Emergency and intensive care: renal failure. Dialysis management; Ergocalciferols - administration & dosage; Ergocalciferols - adverse effects; Female; General and cellular metabolism. Vitamins; Humans; Hypercalcemia - etiology; Hyperparathyroidism, Secondary - blood; Hyperparathyroidism, Secondary - drug therapy; Hyperparathyroidism, Secondary - etiology; Intensive care medicine; Male; Medical sciences; Middle Aged; Naphthalenes - administration & dosage; Naphthalenes - adverse effects; Parathyroid Hormone - blood; Pharmacology. Drug treatments; Receptors, Calcitriol - agonists; Renal Dialysis; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - therapy; Treatment Outcome; Vitamin D - administration & dosage; Endocrinopathy; Agonist; Calcimimetic agent; Hemodialysis; Peptide hormone; Antihormone; Extrarenal dialysis; Vitamin D; Parathyroid diseases; Hydrochlorides; Paricalcitol; cinacalcet hydrochloride; Human; Kidney disease; Urinary system disease; secondary hyperparathyroidism; Low dose; haemodialysis; Treatment; Parathyroid hormone; Analog; Renal failure; Cinacalcet; Comparative study; Hyperparathyroidism
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/gfs018

Optimal treatment for secondary hyperparathyroidism (SHPT) has not been defined. The IMPACT SHPT (ClinicalTrials.gov identifier: NCT00977080) study assessed whether dose-titrated paricalcitol plus supplemental cinacalcet only for hypercalcaemia is superior to cinacalcet plus low-dose vitamin D in controlling intact parathyroid hormone (iPTH) levels in patients with SHPT on haemodialysis. In this 28-week, multicentre, open-label Phase 4 study, participants were randomly selected to receive paricalcitol or cinacalcet plus low-dose vitamin D. Randomization and analyses were stratified by mode of paricalcitol administration [intravenous (IV) or oral]. The primary efficacy end point was the proportion of subjects who achieved a mean iPTH value of 150-300 pg/mL during Weeks 21-28. Of 272 subjects randomized, 268 received one or more dose of study drug; 101 in the IV and 110 in the oral stratum with two or more values during Weeks 21-28 were included in the primary analysis. In the IV stratum, 57.7% of subjects in the paricalcitol versus 32.7% in the cinacalcet group (P = 0.016) achieved the primary end point. In the oral stratum, the corresponding proportions of subjects were 54.4% for paricalcitol and 43.4% for cinacalcet (P = 0.260). Cochran-Mantel-Haenszel analysis, controlling for stratum, revealed overall superiority of paricalcitol (56.0%) over cinacalcet (38.2%; P = 0.010) in achieving iPTH 150-300 pg/mL during Weeks 21-28. Hypercalcaemia occurred in 4 (7.7%) and 0 (0%) of paricalcitol-treated subjects in the IV and oral strata, respectively. Hypocalcaemia occurred in 46.9% and 54.7% of cinacalcet-treated subjects in the IV and oral strata, respectively. Paricalcitol versus cinacalcet plus low-dose vitamin D provided superior control of iPTH, with low incidence of hypercalcaemia.