ASN Kidney Week late-breaking clinical studies highlight advances in kidney care

(Press-News.org) Philadelphia, PA (November 15, 2014) -- The results of numerous high-impact clinical trials that could affect kidney-related medical care will be presented at ASN Kidney Week 2014, November 11-16 at the Pennsylvania Convention Center in Philadelphia, PA.

Among the studies are the following (presented in numerical order):

SA-PO1092 A Randomized Multicomponent Intervention to Reduce Disparities in Transplant Referral: Interim Results from the RaDIANT Community Study -- Rachel E. Patzer, Leighann Sauls, Jennifer C. Gander, M. Ahinee Amamoo, Laura Plantinga, Debra D. Evans, Eric M. Gibney, Laura L. Mulloy, Stephen O. Pastan. Atlanta, GA.

The Southeastern United States, and in particular the state of Georgia, has the lowest rate of kidney transplantation in the nation. The Reducing Disparities In Access to kidNey Transplantation (RaDIANT) Community Study was developed by the academic and community partnership the Southeastern Kidney Transplant Coalition of Georgia, North Carolina, and South Carolina to reduce disparities in access to kidney transplantation among African American End Stage Renal Disease patients. We randomized 134 dialysis facilities in GA that had racial disparity in referral and/or low transplant referral to receive several provider and patient education and engagement interventions (n=67) or no intervention (n=67) over a period of one year (Jan-Dec 2013) in order to improve transplant referrals. Intervention activities included educational webinars for staff, staff- and patient-level educational activities, monthly monitoring of quality improvement activities, and traditional quality improvement oversight of transplant referral overseen by our Southeastern Kidney Transplant Coalition partner End Stage Renal Disease Network 6.

Interim 6-month results among intervention facilities show that the proportion of patients referred for transplant within a facility more than doubled among all of the intervention patients, and more than tripled among African American patients. By 6 months, more than half of the dialysis facilities had eliminated racial disparity in kidney transplant referrals. While the intervention is ongoing through Dec. 2014, preliminary results suggest that the interventions delivered in the RaDIANT Community may increase access to transplant referral and reduce African American vs. white racial disparity in transplant referral access. Longer-term follow-up is needed to examine how these interventions impact access to waitlisting and transplantation. The integration of a sustainable, long-term community-based intervention to improve access to kidney transplant referrals may have a long-lasting impact on the reduction of disparities in kidney transplantation.

SA-PO1093 Envarsus XR (Once-Daily MeltDose Tacrolimus Tablets) Shows Continued Dose Reduction and Similar Efficacy and Safety vs. Prograf (Twice-Daily Tacrolimus Capsules) at Two-Years: Results of a Phase 3, Double-Blind, Randomized Study in De Novo Kidney Transplant Patients -- Lionel Rostaing, Suphamai Bunnapradist. Toulouse Cedex, France.

"Veloxis Pharmaceuticals A/S (OMX: VELO) two-year results of the pivotal Phase 3 clinical trial, Study 3002, of Envarsus® XR (tacrolimus extended-release tablets) in de novo kidney transplant patients continued to demonstrate non-inferior safety and efficacy with continued dose reduction with its once-daily formulation when compared to tacrolimus twice-daily capsules (Prograf®; Astellas Pharma). The two-years results of the double-blind, internationally conducted trial in de novo adult kidney transplant patients treated for 12 months, with a 12-month blinded extension period showed that Envarsus XR was non-inferior to Prograf in the prevention of treatment failure; the overall incidence of treatment failure within 24 months was, Envarsus XR: 23.1%; Prograf: 27.3%. As with the one-year results, at two years, the trough levels were similar and the total daily dose for Envarsus XR was approximately 25% lower vs. Prograf. Renal function and the safety events reported were comparable between the groups over the 2 year study.

The study results demonstrated that during long-term outpatient therapy from Month 12 onwards, Envarsus XR patients continued to require a daily dose that was approximately 25 percent lower than patients receiving Prograf, reflecting the improved bioavailability provided by Veloxis' proprietary MeltDose® formulation."

SA-PO1102 Ferric Citrate Safely Controls Phosphorus, Delivers Iron, and Reduces IV Iron/ESA in ESRD: A 48-Week Clinical Trial -- Julia Lewis, Kausik Umanath, Mohammed Sika, Mark Koury, Peale Chuang, Gerald Schulman, Robert M. Niecestro, Tom Greene, Jamie P. Dwyer, The Collaborative Study Group. Nashville, TN.

Patients with ESRD require multiple medications to manage both their bone and mineral metabolic disturbances and their chronic anemia. The PERFECTED study (PhosphatE binding and iRon delivery with Ferric CiTrate in EsrD) demonstrated that ferric citrate was a highly effective phosphate binder in a 4-week placebo controlled period and achieved similar serum phosphorus levels compared to active control in a 52-week active control period requiring fewer doses compared to sevelemar carbonate to achieve this. In addition and importantly in the 52-week active control period, ferric citrate had highly statistically significant and beneficial effects on these subjects chronic anemia including; increased iron stores as evidenced by increased serum ferritin and TSAT; decreased IV iron and ESA usage; and sustained hemoglobin compared to active control. These findings were associated with an excellent safety profile with fewer subjects experiencing any SAE, an infection (ID) associated SAE, a cardiovascular (CV) associated SAE or a gastrointestinal (GI) associated SAE compared to active control. Subsequent analysis also demonstrated significant projected health care cost savings related to reduced hospitalizations and reduced usage of IV iron and ESA. The study reported here at ASN is a 48-week pragmatic trial that enrolled 168 of the 441 subjects that participated in the PERFECTED study in an additional 48-week trial where all subjects received ferric citrate. Over the 48-week trial serum phosphorus was again well controlled with ferric citrate (mean baseline serum phosphorus 5.7 mg/dL, 48-week serum phosphorus 5.2 mg/dL). On ferric citrate, iron stores increased and the study demonstrated plateauing of both the serum ferritin and the TSAT at 48 weeks. This supports the hypothesis that iron absorption from ferric citrate is tightly regulated in the GI tract. IV iron and ESA usage were again decreased over time and hemoglobin levels sustained. In this study 60% of the subjects never required a single dose of IV iron and in the last 12 weeks of this study 85% of subjects were not receiving IV iron. This is in contrast to the DOPPS data which reports 70-80% of dialysis patients are receiving IV iron at any given time. Ferric citrate use extended now over an additional 48 weeks also had a safety profile comparable to that reported during the original 52 week trial as evidenced by a similar occurrence of overall SAE's, and specifically ID, CV and GI associated SAE's. The use of ferric citrate over 100 weeks retains its efficacy and safety profiles with iron stores plateauing and no safety concerns identified. SA-PO1103 Safety and Efficacy of Modified-Release Calcifediol for Secondary Hyperparathyroidism in Patients with Stage 3 or 4 CKD and Vitamin D Insufficiency -- Stuart M. Sprague, Shaukat Ali, Roberto Mangoo-Karim, Paul W. Crawford, Pablo E. Pergola, Laurel Sindelar, Stephen A Strugnell, Joel Z. Melnick, Jay A. White, Martin P. Petkovich, Charles W. Bishop. Chicago, IL. New Vitamin D Repletion Therapy Effectively Controls Secondary Hyperparathyroidism in Chronic Kidney Disease

A modified-release (MR) oral formulation of calcifediol was reported as effective in treating secondary hyperparathyroidism in predialysis patients exhibiting vitamin D insufficiency, based on data from two recently completed and identical double-blind phase 3 trials and an ongoing open-label extension study. The trials involved 429 patients with stage 3 or 4 chronic kidney disease (CKD), elevated intact plasma parathyroid hormone (iPTH) and vitamin D insufficiency (defined as serum 25-hydroxyvitamin D END