Paricalcitol- or cinacalcet-centred therapy affects markers of bone mineral disease in patients with secondary hyperparathyroidism receiving haemodialysis: results of the IMPACT-SHPT study.
BACKGROUND
In this Phase 4 international study, efficacy and safety of paricalcitol-centred therapy were compared with that of cinacalcet-centred therapy for the treatment of chronic kidney disease (CKD)-associated secondary hyperparathyroidism (SHPT) in patients undergoing haemodialysis (ClinicalTrials.gov identifier NCT00977080).


METHODS
Patients ≥ 18 years of age with Stage 5 CKD and SHPT [intact parathyroid hormone (iPTH) level of 300-800 pg/mL, calcium level of 8.4-10.0 mg/dL and phosphate concentration of ≤ 6.5 mg/dL] who were undergoing haemodialysis were included. Patients were randomized by mode of paricalcitol administration [i.e. intravenous (IV) or oral strata] to receive paricalcitol- or cinacalcet-centred therapy for ≤ 28 weeks. Changes in metabolic markers [total alkaline phosphatase (AP), bone-specific AP and fibroblast growth factor-23 (FGF-23)] and the proportion of patients in each treatment group who achieved an iPTH level of 150-300 pg/mL during Weeks 8, 16 and 21-28 as a composite value were evaluated.


RESULTS
Compared with cinacalcet-centred therapy, levels of both bone turnover markers were significantly reduced from baseline with IV and oral paricalcitol-centred treatment (P < 0.05 for both dosing strata) at Weeks 8, 16 and 28. Levels of FGF-23 were increased with paricalcitol versus cinacalcet-centred treatment. A greater proportion of patients receiving paricalcitol-centred therapy achieved target iPTH levels (i.e. 150-300 pg/mL) throughout the study in the IV and oral dosing strata compared with patients receiving cinacalcet-centred treatment.


CONCLUSIONS
In patients with CKD and SHPT undergoing haemodialysis, paricalcitol-centred therapy reduced circulating bone turnover markers and iPTH levels and increased FGF-23 levels compared with cinacalcet-centred treatment.


BACKGROUND
ClinicalTrials.gov identifier NCT00977080.
Renal Division, Department of Health Sciences, University of Milan, San Paolo Hospital, Milan, Italy.
Mario
M
Cozzolino
Markus
M
Ketteler
Kevin J
KJ
Martin
Amit
A
Sharma
David
D
Goldsmith
Samina
S
Khan
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000008:administration & dosage*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005500:Follow-Up Studies; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D016896:Treatment Outcome
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; C000717427:FGF23 protein, human; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; C084656:paricalcitol; D000089703:Fibroblast Growth Factor-23; D002118:Calcium; D000069449:Cinacalcet
bone turnover marker; chronic kidney disease; cinacalcet; paricalcitol; secondary hyperparathyroidism