Jun 28 2010
Results from the ADVANCE study presented in a late breaking clinical trial session at the ERA-EDTA 2010 Congress provide new insights into the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients. ADVANCE (A randomiseD VAscular calcificatioN study to evaluate the effects of CinacalcEt) is a randomised, controlled open label study to evaluate the effects of treatment with Mimpara® (cinacalcet) plus low-dose vitamin D, compared to flexible doses of vitamin D alone, on the progression of vascular and valvular calcification in dialysis patients with SHPT. A trend was observed towards slower progression of vascular calcification at all sites evaluated among patients randomised to the cinacalcet arm, though the primary endpoint did not reach statistical significance.
The primary endpoint for the study was percentage change in the Agatston CAC score from baseline to week 52. Agatston CAC scores [median, (Q1, Q3)] increased by 24 percent (-1 percent, 63 percent) from baseline in the cinacalcet group and by 31 percent (8 percent, 81 percent) in the flexible vitamin D group>
"Coronary artery calcification is common in dialysis patients and has been linked to an elevated risk of cardiovascular events and mortality in patients on dialysis," said Paolo Raggi, M.D., Professor of Medicine, Emory University School of Medicine, Atlanta, USA. "Although the results for the primary endpoint were not statistically significant, the findings from ADVANCE further support the hypothesis that treatment with cinacalcet plus low doses of vitamin D may slow the progression of this marker of risk in patients on dialysis with SHPT."
ADVANCE also showed that cinacalcet plus low-dose vitamin D, compared to flexible doses of vitamin D alone, provided better biochemical control of SHPT as judged by the blood levels of parathyroid hormone (PTH), calcium, and phosphorus from baseline to the end of the study as demonstrated in previous studies.(1,2) Median (interquartile range) plasma PTH levels decreased by 132 pg/mL (-276,-24) from baseline to study end in the cinacalcet group and by 65 pg/mL (-184, 62) in the flexible vitamin D group>
"The results from ADVANCE, coupled with recently published data, including an observational study showing that cinacalcet significantly improved all-cause and cardiovascular survival in dialysis patients(3), underscore the importance of completing the ongoing EVOLVE (EValuation Of Cinacalcet Therapy to Lower CardioVascular Events™) trial, a global, randomised, placebo-controlled, double-blind study evaluating the impact of cinacalcet on mortality and cardiovascular events in dialysis patients," said Chris Mix, Executive Medical Director of Global Development at Amgen. "We look forward to sharing those results with the nephrology community when they become available."
Additional analyses presented at the ERA-EDTA 2010 Congress provide further support for the hypothesis that treatment with cinacalcet plus low doses of vitamin D may favourably affect the progression of calcification of cardiac valves compared to vitamin D alone(4) (Abstract Number: Sa116); highlight predictors of cardiovascular calcification in patients on dialysis(5) (Abstract Number: OSu039) and compare cardiovascular calcium scoring methods in the ADVANCE study(6) (Abstract Number: OM016).
ADVANCE Study Design
ADVANCE is a randomised, controlled trial to compare two treatment strategies for SHPT and their effects on the progression of CAC among patients on dialysis. ADVANCE studied 360 patients with SHPT and detectable CAC who were randomised to open label treatment with cinacalcet (30-180 mg/day) plus low-dose vitamin D (less than or equal to 2 ug IV paricalcitol equivalent/dialysis session) or to flexible vitamin D therapy. In both groups, calcium-based phosphate binders were used exclusively, and the therapeutic target for PTH was 150-300 pg/mL.
The primary endpoint for ADVANCE evaluated the percentage change in Agatston CAC score from baseline to week 52. Secondary endpoints for ADVANCE included:
- Absolute change from baseline in CAC score at week 52
- Absolute and percentage change from baseline in aortic calcification score at week 52
- Absolute and percentage change from baseline in aortic and mitral valve calcification score at week 52
- Proportion of patients achieving > 15% progression of CAC at week 52
- Absolute and percentage changes in laboratory parameters (PTH, calcium, phosphorus)
- Safety and tolerability of cinacalcet