F. Llach et al., SUPPRESSION OF PARATHYROID-HORMONE SECRETION IN HEMODIALYSIS-PATIENTSBY A NOVEL VITAMIN-D ANALOG - 19-NOR-1,25-DIHYDROXYVITAMIN D-2, American journal of kidney diseases, 32(2), 1998, pp. 48-54
In this double-blind, placebo-controlled, randomized, multicenter stud
y, 35 patients with end-stage renal disease undergoing maintenance hem
odialysis were treated three times weekly for 4 weeks with either 19-n
or-1,25-dihydroxyvitamin D-2 (paricalcitol) intravenously at doses ran
ging from 0.04 to 0.24 mu g/kg or placebo. Eligible patients with seco
ndary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] leve
l > 300 pg/mL) were initially withdrawn from any existing vitamin D th
erapy over a 4-week washout period and then randomized to treatment fo
r 4 weeks with either paricalcitol or placebo. Overall, there was a cl
inically and statistically significant reduction in iPTH level for pat
ients receiving paricalcitol compared with placebo (P = 0.006), The st
udy end point for efficacy was at least a 30% reduction from maximum b
aseline in iPTH level for 75% of the patients receiving paricalcitol p
er dosing group. The study end point for efficacy was at least a 30% r
eduction from maximum baseline in iPTH for 75% of patients receiving p
aricalcitol per dosing group. Sixty-eight percent (15 of 22) of patien
ts receiving paricalcitol attained this efficacy end point regardless
of dosage received (0.04, 0.08, 0.16, and 0.24 mu g/kg), Eighty-three
percent (5 of 6) of the patients in each of the paricalcitol groups re
ceiving 0.16- and 0.24-mu g/kg dosages attained the efficacy end point
. Only two patients receiving placebo attained the iPTH end point. The
re were no clinically relevant differences in serum calcium (Ca) or ph
osphorus (P) levels between the group treated with paricalcitol and th
at treated with placebo. Although there was a statistically significan
t difference between the change from baseline to final-visit Ca levels
in the paricalcitol group and the placebo group (P < 0.001), the fina
l-visit mean Ca level in the paricalcitol group was within the normal
range (9.44 mg/dL). There was no statistically significant difference
between groups for the change from baseline in P level (P = 0.625), On
ly one patient treated with paricalcitol developed hypercalcemia befor
e or coincident with the iPTH end point. Three other patients receivin
g paricalcitol experienced elevated serum Ca levels subsequent to reac
hing the iPTH end point, with iPTH reductions of 83% to 98%. There wer
e no significant differences between patients treated with paricalcito
l and patients treated with placebo in adverse reactions. These result
s show that paricalcitol safely and effectively reduces iPTH levels in
hemodialysis patients with secondary HPT. (C) 1998 by the National Ki
dney Foundation, Inc.