Dr. Daniel Coyne (DC), from Washington University School of Medicine, discusses his abstract for the National Kidney Foundation’s 2014 Spring Clinical Meetings (SCM14), Randomized Multicenter Trial of Paricalcitol Versus Calcitriol for Treatment of Secondary Hyperparathyroidism (SHPT) in Stage 3 and 4 CKD, with Dr. Kenar Jhaveri (eAJKD), eAJKD Editor.
eAJKD: Why don’t you tell us a little about your research and abstract being presented at NKF 2014 Spring Meetings?
DC: The PACE trial (PAricalcitol versus Calcitriol for Efficacy and safety in CKD 3 and 4) compared oral paricalcitol to calcitriol in patients with stage 3 and 4 CKD and secondary hyperparathyroidism. Preclinical studies and placebo-controlled trials of these agents suggested that calcitriol induced significantly more hypercalcemia and hyperphosphatemia than paricalcitol. A meta-analysis was even published suggesting calcitriol poorly controlled PTH and had a very high incidence of hypercalcemia. To test this, we randomized 110 patients to 1 mcg daily of paricalcitol or 0.25 mcg daily of calcitriol, a ratio thought to provide comparable PTH suppression, and then adjusted the dose monthly to achieve 40-60% PTH suppression. The treatment period was 24 weeks. Our primary endpoint was the difference in the incidence of confirmed hypercalcemia between arms. Despite control of PTH to our goal in 98% of paricalcitol patients and 87% of calcitriol patients, and an improvement in alkaline phosphatase, we found an extremely low incidence of hypercalcemia which was similar between groups. Both groups also had changes in serum phosphate and eGFR that were small and similar to what had been observed in the placebo and paricalcitol arms of an earlier trial in a similar patient population. We concluded both calcitriol and paricalcitol achieve sustained PTH and alkaline phosphatase suppression in CKD stage 3 and 4, with small effects on serum calcium and phosphorus, and a low incidence of hypercalcemia.
eAJKD: Do you think one drug is more bone protective for fractures than the other?
DC: We examined markers of high bone turnover, PTH and alkaline phosphatase. Both agents showed similar improvements in these markers. By some parameters, paricalcitol yielded superior PTH suppression, though this may have been due to the initial doses we chose in our trial. Based on our results, the ratio of equipotency for PTH suppression is probably closer to 1 mcg of paricalcitol to 0.37 mcg of calcitriol. Based on changes in PTH and alkaline phosphatase, both agents appear to be efficacious in lowering high bone turnover due to secondary hyperparathyroidism. There were no fractures in our study, and it was far too short and too small to evaluate such an endpoint.
eAJKD: Where do you and your group go from here?
DC: Preclinical trials have demonstrated higher doses of calcitriol promote significant vascular calcification, while much higher doses of paricalcitol that suppress PTH more and induce similar changes in calcium and phosphate fail to cause nearly as much vascular calcification. Epidemiological studies suggest active vitamin D products are associated with improved survival and paricalcitol may be superior to other agents. Those studies suggest there are important non-PTH related differences between these products. We need randomized outcome trials using these agents in CKD 3 and 4 to examine their effects on fractures, parathyroidectomy rates, and renal and cardiovascular outcomes.
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