A Randomized Trial of Cinacalcet versus Vitamin D Analogs as Monotherapy in Secondary Hyperparathyroidism (PARADIGM)

Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1031-40. doi: 10.2215/CJN.07050714. Epub 2015 Apr 22.


Background and objectives: Direct comparison of cinacalcet and vitamin D analogs as monotherapies to lower parathyroid hormone (PTH) levels has not been undertaken.

Design, setting, participants, & measurements: This was a prospective, multicenter, phase 4, randomized, open-label study that enrolled participants from 2010 to 2012. Adult participants (n=312) on hemodialysis with PTH >450 pg/ml were randomized 1:1 to 12 months of treatment with either cinacalcet (n=155) or vitamin D analogs (n=157) to evaluate the mean percentage change in plasma PTH level (primary end point) and the proportion of participants achieving plasma PTH <300 pg/ml or a ≥30% decrease in PTH (secondary end points). A preplanned analysis to determine whether there were important region-by-treatment interactions was also undertaken.

Results: Baseline mean PTH was 846 pg/ml (n=155) for cinacalcet and 816 pg/ml (n=157) for vitamin D analog therapy. The mean (95% confidence interval) percentage change from baseline in PTH was -12.1% (-20.0% to -4.1%) in the cinacalcet arm and -7.0% (-14.9% to 0.8%) in the vitamin D analog arm, a difference of -5.0% (-15.4% to 5.4%) (P=0.35). Similarly, there was no difference in achievement of secondary efficacy end points between arms (19.4% and 15.3% of participants with PTH≤300 pg/ml and 42.6% and 33.8% of participants had a PTH reduction >30% in the cinacalcet and vitamin D analog arms, respectively). A prespecified analysis revealed a large treatment-by-region interaction, with nominally greater response to cinacalcet compared with vitamin D analogs in non-United States participants (US versus non-US participants, P<0.001). Hypocalcemia was more common in the cinacalcet arm, whereas hypercalcemia and hyperphosphatemia occurred more often in the vitamin D analog arm.

Conclusions: Participants had similar modest reductions in PTH with either cinacalcet or vitamin D analog monotherapy over 52 weeks of treatment, but effects varied by region. Treatments differed with regard to effect on calcium and phosphorus levels.

Trial registration: ClinicalTrials.gov NCT01181531.

Keywords: CKD; ESRD; dialysis.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Australia
  • Biomarkers / blood
  • Calcimimetic Agents / adverse effects
  • Calcimimetic Agents / therapeutic use*
  • Canada
  • Cinacalcet / adverse effects
  • Cinacalcet / therapeutic use*
  • Female
  • Humans
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / diagnosis
  • Hyperparathyroidism, Secondary / drug therapy*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / therapy*
  • Male
  • Parathyroid Hormone / blood
  • Prospective Studies
  • Renal Dialysis* / adverse effects
  • Russia
  • Time Factors
  • Treatment Outcome
  • United States
  • Vitamin D / adverse effects
  • Vitamin D / analogs & derivatives
  • Vitamin D / therapeutic use*


  • Biomarkers
  • Calcimimetic Agents
  • PTH protein, human
  • Parathyroid Hormone
  • Vitamin D
  • Cinacalcet

Associated data

  • ClinicalTrials.gov/NCT01181531