The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale

Abstract Background Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis. Methods/Design The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An “oxidative stress” substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months. Discussion FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon. Trial registration ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-2

Impact of Transdermal Oxybutynin on Work Productivity in Patients with Overactive Bladder: Results from the MATRIX Study

Background Overactive bladder syndrome (OAB) is a common condition affecting a significant number of working adults, resulting in increased healthcare utilization, reduced quality of life and decreased work productivity. The MATRIX study was a large, prospective, community-based, observational US study aimed at evaluating the impact of oxybutynin transdermal system (OXY-TDS). In this paper, we report on productivity findings among working adults in MATRIX. Abstract: Methods This study enrolled 2878 adults (aged ≥18 years) with symptoms of OAB from 327 practice sites throughout the US. All subjects received OXY-TDS (3.9 mg/day up to 6 months). Baseline versus end-of-study productivity was measured using the Work Productivity Questionnaire (WPQ). The WPQ includes a subset of questions from the Work Limitations Questionnaire (WLQ) and consists of four scales: (i) physical; (ii) time management; (iii) mental; and (iv) output demands. Overall productivity was measured by the work productivity index score (WPQ Index; a summary score based on scales) and work productivity loss score (WPLS; a measure of reduced output compared with healthy workers). Psychometric performance of the WPQ instrument is also reported, since this study represents the first use of the tool. Abstract: Results Of the participants, 52% were of working age (18-65 years) and 38.6% were employed. A total of 1112 working adults participated in MATRIX and were included in this analysis. They had a mean age of 52.4 years; 92.2% were female and 80.9% were Caucasian. Subjects who reported that they were most affected by OAB were also most impaired at work. After OXY-TDS treatment, participants experienced significant improvements in mean scores for all four WPQ scales (p ≤ 0.0002) and the mean WPQ Index decreased from 8.2 to 5.5 (p < 0.0001). In addition, the WPLS decreased from 7.7% to 5.2% (p < 0.0001), indicating improvement in work function with OXY-TDS treatment. Abstract: Conclusion OAB contributes to decreased work productivity due to job interruptions as well as fatigue. OXY-TDS may result in productivity improvement when patients receive 3.9 mg/day via twice weekly patch application for up to 6 months.

Ferric Gluconate Reduces Epoetin Requirements in Hemodialysis Patients with Elevated Ferritin

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) ≤25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of −7527 ± 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 ± 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml