Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism.
Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.
Frazão
J M
JM
Medical and Research Services, Veterans Affairs West Los Angeles Healthcare Center, Los Angeles, CA, USA.
Elangovan
L
L
Maung
H M
HM
Chesney
R W
RW
Acchiardo
S R
SR
Bower
J D
JD
Kelley
B J
BJ
Rodriguez
H J
HJ
Norris
K C
KC
Robertson
J A
JA
Levine
B S
BS
Goodman
W G
WG
Gentile
D
D
Mazess
R B
RB
Kyllo
D M
DM
Douglass
L L
LL
Bishop
C W
CW
Coburn
J W
JW
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D002118:Calcium / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood
D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; C042533:1 alpha-hydroxyergocalciferol; D000469:Alkaline Phosphatase; D002118:Calcium