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C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial.

ABSTRACT: This study examined the efficacy of C.E.R.A., a continuous erythropoietin receptor activator, for correcting anemia in patients who had chronic kidney disease (CKD) and were not on dialysis.In this open-label, randomized, parallel-group, Phase III study, 324 adult patients with CKD not on dialysis nor receiving treatment with erythropoiesis-stimulating agents (ESAs) were randomly assigned (1:1) to receive subcutaneous C.E.R.A. once every 2 wk or darbepoetin alfa once weekly during an 18-wk correction period and a 10-wk evaluation period. Thereafter, patients receiving C.E.R.A. were randomly assigned to C.E.R.A. once every 2 wk or once monthly, and patients receiving darbepoetin alfa could receive darbepoetin alfa once weekly or once every 2 wk for a 24-wk extension period. Dosage was adjusted to achieve a hemoglobin (Hb) response and to maintain Hb +/-1 g/dl of the response level and 11 to 13 g/dl. Primary end points were Hb response rate during correction and evaluation and change in Hb concentration between baseline and evaluation.Hb response rates were 97.5% for C.E.R.A. and 96.3% for darbepoetin alfa. Adjusted mean changes in Hb from baseline to evaluation were 2.15 g/dl (C.E.R.A.) and 2.00 g/dl (darbepoetin alfa). Analysis showed that C.E.R.A. once every 2 wk was as effective as darbepoetin alfa once weekly for correcting anemia. Hb levels remained stable in all groups during the extension period. C.E.R.A. and darbepoetin alfa were well tolerated.Subcutaneous C.E.R.A. once every 2 wk corrects anemia in ESA-naïve patients who are not on dialysis.

SUBMITTER: Macdougall IC

PROVIDER: S-EPMC2390949 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial.

Macdougall Iain C IC Walker Rowan R Provenzano Robert R de Alvaro Fernando F Locay Harold R HR Nader Paul C PC Locatelli Francesco F Dougherty Frank C FC Beyer Ulrich U

Clinical journal of the American Society of Nephrology : CJASN 20080220 2

<h4>Background and objectives</h4>This study examined the efficacy of C.E.R.A., a continuous erythropoietin receptor activator, for correcting anemia in patients who had chronic kidney disease (CKD) and were not on dialysis.<h4>Design, setting, participants, & measurements</h4>In this open-label, randomized, parallel-group, Phase III study, 324 adult patients with CKD not on dialysis nor receiving treatment with erythropoiesis-stimulating agents (ESAs) were randomly assigned (1:1) to receive sub ...[more]

PMID: 18287255

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Project description:ImportanceDaprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported.ObjectiveTo evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients.Design, setting, and participantsThis prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete.InterventionsRandomized 1:1 to daprodustat or darbepoetin alfa.Main outcomes and measuresThe primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability.ResultsA total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.Conclusions and relevanceThis randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population.Trial registrationClinicalTrials.gov Identifier: NCT03029208.

Project description:BackgroundPegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies.MethodsA randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691.FindingsThree hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported.InterpretationMonthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients.FundingThe study was supported by Hansoh Medical Development Group.

Project description:ImportanceMajor depressive disorder (MDD) is prevalent among patients with chronic kidney disease (CKD) and is associated with morbidity and mortality. The efficacy and adverse events of selective serotonin reuptake inhibitors in these patients are unknown.ObjectiveTo determine whether treatment with sertraline improves depressive symptoms in patients with CKD and MDD.Design, setting, and participantsThe Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) was a randomized, double-blind, placebo-controlled trial involving 201 patients with stage 3, 4, or 5 non-dialysis-dependent CKD, who were enrolled at 3 US medical centers. The Mini Neuropsychiatric Interview was used to establish MDD. The first participant was randomized in March 2010 and the last clinic visit occurred in November 2016.InterventionsAfter a 1-week placebo run-in, participants were randomized to sertraline (n = 102) for 12 weeks at an initial dose of 50 mg/d (escalated to a maximum dose of 200 mg/d based on tolerability and response) or matching placebo (n = 99).Main outcomes and measuresThe primary outcome was improvement in depressive symptom severity from baseline to 12 weeks determined by the 16-item Quick Inventory of Depression Symptomatology-Clinician Rated (QIDS-C16) (score range, 0-27; minimal clinically important difference, 2 points). Secondary outcomes included improvement in quality of life (Kidney Disease Quality of Life Survey-Short Form; score range, 0-100; higher scores indicate more favorable quality of life) and adverse events.ResultsThere were 201 patients (mean [SD] age, 58.2 [13.2] years; 27% female) randomized. The primary analysis included 193 patients who had at least 1 outcome assessment after randomization. The mean (SD) baseline QIDS-C16 score was 14.0 (2.4) in the sertraline group (n = 97) and 14.1 (2.4) in the placebo group (n = 96). The median participation time was 12.0 weeks and the median achieved dose was 150 mg/d, which was not significantly different between the groups. The QIDS-C16 score changed by -4.1 in the sertraline group and by -4.2 in the placebo group (between-group difference, 0.1 [95% CI, -1.1 to 1.3]; P = .82). There was no significant between-group difference in change in patient-reported overall health on the Kidney Disease Quality of Life Survey (median score, 0 in the sertraline group vs 0 in the placebo group; between-group difference, 0 [95% CI, -10.0 to 0]; P = .61). Nausea or vomiting occurred more frequently in the sertraline vs placebo group (22.7% vs 10.4%, respectively; between-group difference, 12.3% [95% CI, 1.9% to 22.6%], P = .03), as well as diarrhea (13.4% vs 3.1%; between-group difference, 10.3% [95% CI, 2.7% to 17.9%], P = .02).Conclusions and relevanceAmong patients with non-dialysis-dependent CKD and MDD, treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. These findings do not support the use of sertraline to treat MDD in patients with non-dialysis-dependent CKD.Trial registrationclinicaltrials.gov Identifier: NCT00946998.

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C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial.

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C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial.

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