title: A Randomized Trial of Cinacalcet versus Vitamin D Analogs as Monotherapy in Secondary Hyperparathyroidism (PARADIGM).
abstract: OBJECTIVE
  Direct comparison of cinacalcet and vitamin D analogs as monotherapies to lower parathyroid hormone (PTH) levels has not been undertaken.
  
  
  METHODS
  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.
authors.affiliation: Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota; james.wetmore@hcmed.org.
authors.forename: James B
authors.initials: JB
authors.lastname: Wetmore
authors.affiliation: Fresenius Medical Care, St. Petersburg, Russia;
authors.forename: Konstantin
authors.initials: K
authors.lastname: Gurevich
authors.affiliation: Division of Nephrology and Hypertension, NorthShore University HealthSystem, Evanston, Illinois;
authors.forename: Stuart
authors.initials: S
authors.lastname: Sprague
authors.affiliation: Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;
authors.forename: Gerald
authors.initials: G
authors.lastname: Da Roza
authors.affiliation: Columbia Nephrology Associates, Columbia, South Carolina; and.
authors.forename: John
authors.initials: J
authors.lastname: Buerkert
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Maureen
authors.initials: M
authors.lastname: Reiner
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: William
authors.initials: W
authors.lastname: Goodman
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Kerry
authors.initials: K
authors.lastname: Cooper
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D015415:Biomarkers / Q000097:blood; D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D000069449:Cinacalcet / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects; D012426:Russia; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014807:Vitamin D / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D057966:Calcimimetic Agents; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D000069449:Cinacalcet
keywords: CKD; ESRD; dialysis