60 research outputs found
Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS)
No full textBACKGROUND: Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of chronic kidney disease (CKD) anemia. METHODS: This Phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with Stages 3-5 CKD, not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52-104 weeks. This study examined two primary efficacy endpoints: European Union (European Medicines Agency)-hemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that increased from baseline (BL) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; US Food and Drug Administration-change in Hb from BL to the average Hb level during Weeks 28-52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined. RESULTS: A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response [odds ratio = 34.74, 95% confidence interval (CI) 20.48-58.93] and change in Hb from BL [roxadustat - placebo: +1.692 (95% CI 1.52-1.86); both P < 0.001]. Superiority of roxadustat was demonstrated for low-density lipoprotein cholesterol change from BL, and time to first use of rescue medication (both P < 0.001). The incidences of treatment-emergent adverse events were comparable between groups (roxadustat: 87.7%, placebo: 86.7%). CONCLUSIONS: Roxadustat demonstrated superior efficacy versus placebo in terms of both Hb response rate and change in Hb from BL. The safety profiles of roxadustat and placebo were comparable
Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies
No full textIntroduction: This study was conducted to elucidate the safety of roxadustat, an oral medication, in patients with non-dialysis-dependent (NDD) or incident dialysis dialysis-dependent (ID-DD) chronic kidney disease (CKD). Methods: Safety results from four phase 3, randomized, open-label studies comparing roxadustat to an erythropoiesis-stimulating agent (ESA) in men and women with NDD or ID-DD CKD with anemia were pooled and evaluated. Endpoints were time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality) and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), all-cause mortality, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for non-inferiority at 1.8- and 1.3-margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized. Results: In total, 2142 patients were evaluated (1083 roxadustat; 1059 ESA). Roxadustat was comparable to ESA for risk of MACE (HR 0.79, 95% CI 0.61–1.02), MACE+ (HR 0.78, 95% CI 0.62–0.98), and all-cause mortality (HR 0.78, 95% CI 0.57–1.05). TEAEs were comparable between roxadustat and ESA groups, including any TEAE [incidence rate per 100 (IR/100) patient-exposure years 56.1 vs. 53.5], TEAEs leading to study drug discontinuation (IR/100 patient-exposure years 6.7 vs. 5.1), and TEAEs leading to death (IR/100 patient-exposure years 6.9 vs. 7.4). Conclusion: There was no evidence of increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DD CKD. Although TEAEs occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued the study drug because of an adverse event. Clinical Trial Registration Numbers: DOLOMITES, 1517-CL-0610 [NCT02021318]; HIMALAYAS, FGCL-4592-063 [NCT02052310]; SIERRAS, FGCL-4592-064 [NCT02273726]; and ROCKIES, D5740C00002 [NCT02174731]
Impact of the beta 1-Adrenoceptor Arg389Gly Polymorphism on Heart-Rate Responses to Bisoprolol and Carvedilol in Heart-Failure Patients
No full textThis pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the beta 1-adrenoceptor Arg189Gly polymorphism on heart-rate responses to bisoprolol or carvedilol in elderly patients with heart failure (421 with sinus rhythm, 107 with atrial fibrillation). Patients were randomized 1:1 to bisoprolol or carvedilol with a fortnightly dose-doubling scheme and guideline target doses. Patients with sinus rhythm responded essentially identically to bisoprolol and carvedilol, independent of genotype. Atrial fibrillation patients homozygous for Arg389 had a much smaller response to carvedilol than carriers of at least one Gly389 allele (mean difference 12 bpm, P < 0.00001). Carvedilol up to 2 x 12.5 mg did not reduce heart rate in Arg389Arg homozygotes at all. Interestingly, the immediate response to carvedilol did not differ between genotypes. The Arg389Gly polymorphism has a major impact on the heart-rate response to carvedilol (but not bisoprolol) in patients with heart failure plus atrial fibrillation
P6163Improvement of the cardiac hemodynamic performance among dialysis patients with end-stage renal disease by active fluid management modulation
No full textSupplementary Material for: Randomized, Double-Blind, Placebo-Controlled, Withdrawal Study of Colestilan after Dose Titration in Chronic Kidney Disease Dialysis Patients with Hyperphosphatemia
No full textBackground/Aims: Colestilan is a new non-calcium-based phosphate binder licensed in Europe for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis (CKD 5D). This study was conducted to evaluate efficacy in a North American patient population and also to examine secondary actions of colestilan on lipid profile and glycated hemoglobin (HbA1c). Methods: This was a multicenter, randomized, double-blind, placebo-controlled withdrawal study, after an initial open-label titration period. Patients (n = 245) with stable phosphate control received 6-15 g/day colestilan during a 12-week, flexible titration period after which 169 were randomized to continue the same dose (n = 85) or switch to placebo (n = 84) for 4 weeks. The primary endpoint was the change in serum phosphorus level during the placebo-controlled withdrawal period. Results: A significant difference of -1.01 mg/dl (-0.33 mmol/l) in mean change in serum phosphorus, favoring colestilan, was seen during the placebo-controlled withdrawal period (p Conclusion: In this first clinical trial with colestilan in a North American patient population, colestilan demonstrated significant efficacy in controlling serum phosphorus levels in CKD 5D patients with hyperphosphatemia, without increasing calcium levels
Association between age and cardiovascular status by echosonography in asymptomatic predialysis patients with chronic kidney disease
No full textAge is an important risk factor for cardiovascular disease in the general population and in dialysis patients. The aim of this study is to investigate the influence of age on the cardiovascular status of asymptomatic predialysis patients with chronic kidney disease (CKD). Echocardiography and carotid ultrasound were performed in 61 patients with CKD stages 4–5, who were divided by age into two groups: group 1 (≥65 years, n = 31) and group 2 (<65 years, n = 30). Data were compared with those of control group (≥65 years, n = 20). Group 1 patients had significantly higher left ventricular mass index (LVMI), (P <0.001), worse LV diastolic function (lower E/A ratio: P<0.05, E’ velocities: P< 0.001, E’/A’ ratio: P <0.001, and a higher ratio E/E’: P <0.05) and a higher prevalence of aortic (P <0.01) and mitral calcification (P <0.001) compared to group 2 patients. Elderly patients also had significantly increased intima-media thickness (IMT, P <0.001) and a greater prevalence of carotid plaques (P <0.05) and calcifications (P <0.001) than younger patients. Multiple regression analysis showed that IMT, LVMI, and E/A ratio were independent variables associated with aging (R2 = 0.605). We concluded that older CKD patients demonstrated more profound structural and functional abnormalities of the myocardium, as well as more prominent vascular changes compared to younger CKD patients. The changes in IMT, LVMI, and E/A ratio are independently associated with aging of CKD patients
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