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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Paricalcitol versus cinacalcet plus low-dose vitamin D provided superior control of iPTH, with low incidence of hypercalcaemia.

Fig. 1.

Patient disposition. ^aSome subjects discontinued for multiple reasons. ITT, intent-to-treat.

Fig. 2.

Mean iPTH during treatment by stratum (IV or oral) and treatment group.

Fig. 3.

Proportions of subjects who achieved mean iPTH between 150 and 300 pg/mL during treatment weeks 21–28 in each stratum (A) and overall, based on Cochran–Mantel–Haenszel analysis controlling for stratum (B).

Fig. 4.

Proportions of subjects with ≥30 and ≥50% reduction from baseline in mean iPTH during Weeks 21–28.

Fig. 5.

Proportions of subjects with hypocalcaemia [mean calcium < 8.4 mg/dL (2.09 mmol/L)] and hypercalcaemia [mean calcium >10.5 mg/dL (2.63 mmol/L)] during the evaluation period.