Paricalcitol Versus Cinacalcet in Lowering Parathyroid Hormone Levels in Chronic Kidney Disease

Paricalcitol allowed the achievement of target parathyroid hormone levels better than cinacalcet in patients with secondary hyperparathyroidism (SHPT), a complication of chronic kidney disease (CKD). Both a vitamin D receptor activator such as paricalcitol and a calcimimetic such as cinacalcet effectively treat SHPT, which is characterized by elevated serum levels of intact parathyroid hormone (iPTH). Elevated iPTH levels can lead to skeletal and cardiovascular complications.

Speaking at the 48th Congress of the European Renal Association—European Dialysis and Transplant Association in Prague, Markus Ketteler, MD, of the division of nephrology at the Coburg Clinic in Coburg, Germany, told the congress that the effectiveness of these treatments had never before been compared in patients undergoing hemodialysis.

So he and coworkers performed the Improved Management of iPTH with Paricalcitol-centered Therapy versus Cinacalcet Therapy with Low-dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism (IMPACT SHPT) study to assess the optimal dose titration of paricalcitol (adding cinacalcet if hypercalcemia occurred) in comparison with a combination of cinacalcet with low-dose vitamin D for the treatment of SHPT. The phase 4 study was open label and multinational.

After a screening and washout period, the investigators randomly assigned 272 patients receiving hemodialysis to paricalcitol or to cinacalcet with low-dose vitamin D for 28 weeks. The evaluation period was the final eight weeks of the trial. Patients received paricalcitol intravenously (iv stratum at United States and Russian sites) or orally (oral stratum at all sites other than in the United States or Russia). Patients taking cinacalcet received low-dose vitamin D intravenously (iv) or orally.

At baseline, the patients were well matched within each stratum for age, gender, duration of dialysis, serum calcium, and serum iPTH level (iv stratum, 521 pg/mL and 526 pg/mL; oral stratum, 495 pg/mL and 510 pg/mL for the paricalcitol and cinacalcet arms, respectively). Comorbidities were common and possibly reflected the characteristics of the larger population of patients receiving hemodialysis. Significantly more participants in the paricalcitol group iv stratum had type 1 diabetes, and those in the oral stratum had more type 2 diabetes.

Paricalcitol was initially dosed at 0.07 µg/kg iv or PTH/80 orally. The cinacalcet dose was 30 mg initially. The study inclusion criteria were hemodialysis three times a week for at least three months before entry; an iPTH level between 300 and 800 pg/mL, inclusive; a calcium level of 8.4–10.0 mg/dL; and phosphorus at or below 6.5 mg/dL at baseline.

The primary outcome of the trial was the proportion of participants attaining a mean iPTH value of 150–300 pg/mL during weeks 21 to 28 (normal iPTH is 10–65 pg/mL). A secondary outcome was the proportion of participants with hypocalcemia, defined as a mean serum calcium level of less than 8.4 mg/dL, or with hypercalcemia, defined as a mean calcium level of at least 10.5 mg/dL.

More people receiving paricalcitol achieved iPTH target

In the primary efficacy analysis of reaching the target iPTH level, iv paricalcitol was superior to iv cinacalcet, with fewer patients outside the normal serum calcium range. In the iv stratum, 58 percent of patients receiving paricalcitol achieved the iPTH endpoint versus 33 percent receiving cinacalcet (p = 0.016). However, the patients taking the oral drugs showed no significant difference in the proportion achieving the iPTH target (54 percent with paricalcitol versus 43 percent with cinacalcet; p = 0.26).

In a secondary efficacy analysis that controlled for strata, paricalcitol was superior to cinacalcet, with 56 percent and 38 percent of participants, respectively, falling in the iPTH efficacy range during the evaluation period (p = 0.01).

When the wholesale costs in the United States of paricalcitol, cinacalcet, and vitamin D preparations were calculated, the medication costs for paricalcitol treatment were 40 percent lower than for cinacalcet treatment.

Adverse events

Hypocalcemia occurred in about half of the cinacalcet patients in either the iv or the oral stratum but in only 4 percent in the oral paricalcitol stratum and in none in the iv stratum. Minimal hypercalcemia was observed and was not significantly different between the two drugs taken either iv or orally.

In all, 69–81 percent of subjects in the four groups completed the study. Serious adverse events led to interruption of the study drugs in 22–27 percent of the patients in any of the four arms. When the iv and oral strata were combined, three times as many major adverse cardiovascular events occurred with paricalcitol (9/134) as with cinacalcet (3/134), possibly because of differences in risk factors between the groups at baseline.

In conclusion, Dr. Ketteler said “Paricalcitol showed superiority over cinacalcet in achieving the primary efficacy endpoint” when strata were controlled for. He noted that hypocalcemia occurred in almost half of the patients treated with cinacalcet and that in paricalcitol-treated patients the incidence of hypercalcemia was not significantly different from that in people treated with cinacalcet.

October-November 2011 (Vol. 3, Number 10 & 11)