Abstract: TH-PO513
Effect of Baseline Serum Calcium on Responses to Extended-Release Calcifediol (ERC) in Stage 3-4 CKD
Session Information
- CKD: Clinical Trials and Tubulointerstitial Disorders
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 305 CKD: Clinical Trials and Tubulointerstitial Disorders
Authors
- Kopyt, Nelson P., Lehigh Valley Hospital, Bethlehem, Pennsylvania, United States
- Strugnell, Stephen A., OPKO Health, Miami, Florida, United States
- Ashfaq, Akhtar, OPKO Health, Miami, Florida, United States
- Petkovich, Martin P., Queen's University, Kingston, Ontario, Canada
- Bishop, Charles W., OPKO Health, Miami, Florida, United States
Background
Calcitriol and its 1α-hydroxylated analogs frequently increase serum calcium (Ca) and the risk of vascular calcification in patients with stage 3-4 CKD. For this reason, the revised KDIGO guideline for CKD-Mineral and Bone Disorder suggests that these agents not be routinely used in this population. Randomized clinical trials (RCTs) with ERC, a new FDA-approved therapy for secondary hyperparathyroidism (SHPT), demonstrated effective control of iPTH with minimal changes in serum Ca in stage 3-4 CKD. Data from these RCTs were examined post-hoc to assess the potential impact of baseline serum Ca on end-of-treatment (EOT) serum Ca, phosphorus (P), total 25-hydroxyvitamin D (25D) and total 1,25-dihydroxyvitamin D (1,25D), and on plasma intact parathyroid hormone (iPTH) in ERC-treated and placebo (PL)-treated subjects.
Methods
Two identical, double-blind trials were conducted in 429 subjects with stage 3-4 CKD, SHPT (iPTH >85 pg/mL) and vitamin D insufficiency (25D of 10-29 ng/mL). Subjects were randomized 2:1 to receive ERC (30 or 60 mcg/day) or PL for 26 weeks. Per-protocol data were pooled and analyzed by baseline serum Ca tertile.
Results
The table below shows mean baseline values at left and EOT values at right for ERC tertiles (n= 78 each) and for PL tertiles (n=40-41 each).
ERC and PL had similar effects on mean serum Ca and P irrespective of baseline serum Ca tertile. ERC increased mean serum 25D and 1,25D and decreased mean plasma iPTH to similar levels in all tertiles, with the greatest observed changes occurring in the lowest tertile (T1). PL treatment produced increases in iPTH and no changes in 25D and 1,25D.
Conclusion
Baseline serum Ca affected serum 1,25D and plasma iPTH responses to ERC treatment. ERC-induced increases in 1,25D and decreases in iPTH were greatest in subjects with the lowest baseline Ca.
Table 1
| Serum Ca (mg/dL) | Serum P (mg/dL) | 25D (ng/mL) | 1,25D (pg/mL) | iPTH (pg/mL) | ||||||
| ERC | PL | ERC | PL | ERC | PL | ERC | PL | ERC | PL | |
| T1 | 8.9/9.1 | 8.9/9.0 | 3.8/4.0 | 3.7/3.9 | 20/68 | 19/19 | 32/47 | 37/38 | 157/115 | 147/152 |
| T2 | 9.2/9.4 | 9.3/9.4 | 3.7/3.9 | 3.7/3.9 | 19/68 | 20/18 | 34/47 | 34/38 | 138/109 | 149/161 |
| T3 | 9.5/9.6 | 9.5/9.5 | 3.7/3.9 | 3.7/3.7 | 20/65 | 18/18 | 37/46 | 36/37 | 136/112 | 141/144 |
Funding
- Commercial Support –