Ferric citrate controls phosphorus and delivers iron in patients on dialysis.

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients.

BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. METHODS: Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa-to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline. RESULTS: A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2-13) to 54% (Weeks 18-25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. CONCLUSIONS: The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT00228449.

Patient computer use to prompt doctor adherence to diabetes management guidelines.

RATIONALE, AIMS AND OBJECTIVES: Doctor compliance with diabetic care guidelines is low and may be improved with system-wide changes that include patient involvement. The objective of this study was to determine if patients in an internal medicine teaching clinic would use a touch-screen computer to receive personalized information regarding their need for diabetes care. Outcomes included determining if this intervention would improve resident doctor compliance with diabetic guidelines. METHODS: In this prospective study a computer was available for patients to use independently in one clinic, while another computer was placed in a second clinic with nursing support. Patients responding they were diabetic to the first screen received screens covering HbA1c, blood pressure, cholesterol, foot, eye examinations and compliance with having labs drawn. Non-diabetic patients received three general health screens. A response-based report was printed for patients to share with their doctor. Chart reviews were conducted to assess diabetic health care delivery. RESULTS: The computer was used voluntarily by 20.6% of patients in the primary clinic and by 100% of patients in the nurse-assisted clinic. A total of 104 patients from both clinics responded they were diabetic; over 50% did not know what HbA1c meant and a minority responded their HbA1c, blood pressure and cholesterol were at good levels. Significantly more HbA1c tests conducted within 6 months were documented in patients' charts. DISCUSSION: Patients used the computer effectively without direction in the primary clinic. In this initial study, implementation of the computer program increased the number of HbA1c tests ordered. Future studies incorporating refinements may increase both usage and efficacy of this intervention.

Ischemic colitis revisited: a prospective study identifying hypercoagulability as a risk factor.

BACKGROUND: Although causes for ischemic colitis have been identified, many cases are deemed idiopathic. Some reports suggest an association between ischemic colitis and coagulation disorders. Our purpose was to explore the relationship of ischemic colitis and clotting abnormalities. METHODS: Eighteen patients consented to undergo a hypercoagulability evaluation. Tests included protein C, protein S, activated protein C resistance, factor V Leiden, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor, antithrombin III, anti-smooth muscle antibody, lupus anticoagulant panel, and prothrombin 20210G/A mutation (in women undergoing hormone replacement therapy). RESULTS: Five of 18 patients tested positive for coagulation abnormalities, including factor V and activated protein C resistance, protein S deficiency, prothrombin 20210G/A mutation, and anticardiolipin antibody. CONCLUSION: To our knowledge, this is the largest series of patients with ischemic colitis studied for coagulation defects in the United States. The prevalence of clotting disorders in our study (28%) was higher than that in the general population (8.4%). Coagulation disorders should be considered in some cases of ischemic colitis that are thought to be idiopathic.

Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy.

BACKGROUND/AIMS: Pimagedine inhibits the formation of advanced glycation end products and slows the progression of diabetic complications in experimental models. This study was undertaken to determine if pimagedine ameliorates nephropathy in type 1 (insulin-dependent) diabetes mellitus. METHODS: This was a randomized, double-masked, placebo-controlled study performed in 690 patients with type 1 diabetes mellitus, nephropathy, and retinopathy. The patients received twice daily dosing with placebo, pimagedine 150 mg, or pimagedine 300 mg for 2-4 years. The primary end point was the time to doubling of serum creatinine; the secondary end points included evaluations of proteinuria, kidney function, and retinopathy. RESULTS: Serum creatinine doubled in 26% (61/236) of the placebo-treated patients and in 20% (91/454) of those who received pimagedine (p = 0.099). The estimated glomerular filtration rate decreased more slowly in the pimagedine-treated patients with a 36-month decrease from baseline of 6.26 ml/min/1.73 m(2) as compared with 9.80 ml/min/1.73 m(2) in the placebo-treated patients (p = 0.05), and pimagedine reduced the 24-hour total urinary proteinuria. (The mean reduction from baseline at month 36 was 732 mg/24 h at the low dose and 329 mg/24 h at the high dose as compared with 35 mg/24 h in the placebo group; p

One-day quadruple therapy compared with 7-day triple therapy for Helicobacter pylori infection.

BACKGROUND: Eradication of Helicobacter pylori infection has had an impact on the treatment and recurrence rates of peptic ulcer disease and malignancies such as mucosa-associated lymphoid tissue lymphoma. Treatment options are cumbersome, expensive, and associated with side effects. METHODS: Randomized, prospective, open-labeled equivalence trial with a parallel-group design to compare eradication rates of H pylori with a 1-day, 4-drug regimen with a 7-day, 3-drug regimen. A total of 160 patients with dyspepsia and a Glasgow Dyspepsia Severity Score of at least 3 had a urea breath test labeled with carbon 14. Patients who tested positive were randomized to 1 of the 2 study groups. The study was designed to test the therapeutic equivalence of 1-day and 7-day regimens based on the percentage of H pylori eradication in each group at 5 weeks. RESULTS: The 1-day treatment group (n = 80) had a slightly higher eradication percentage (95%) than the 7-day group (90%). The possible inferiority of the 1-day treatment relative to the 7-day treatment, a 15% difference in the number of patients whose infection was not eradicated at 5 weeks, was rejected (P<.001; 90% confidence interval, 2.7%-11%). Both groups demonstrated a mean decrease of 7.5 points in the Glasgow Dyspepsia Severity Score. The 2 groups showed no significant differences in side effects. Patients whose treatment failed (4 in the 1-day treatment group and 7 in the 7-day treatment group) were re-treated for 10 days. One patient from the 7-day treatment group still tested positive after the second treatment. CONCLUSIONS: The 1-day treatment proved to be statistically similar to the 7-day treatment for the eradication of H pylori in patients with dyspepsia and a positive urea breath test. Further evaluation will be necessary to determine whether the 1-day regimen is adequate for patients with peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, or gastric adenocarcinoma.