Dataset Information

Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies.

ABSTRACT: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease. Two open-label, uncontrolled phase 3 studies evaluated the 52-week safety and efficacy of enarodustat in Japanese anemic patients with chronic kidney disease not on dialysis (n = 132) [SYMPHONY ND-Long study] or on maintenance hemodialysis (n = 136) [SYMPHONY HD-Long study]. The most frequent adverse events were viral upper respiratory tract infection (25.8%) followed by chronic kidney disease (8.3%) in the SYMPHONY ND-Long study, and viral upper respiratory tract infection (49.3%) followed by contusion (16.9%) and diarrhea (16.9%) in the SYMPHONY HD-Long study. The incidence of any adverse events did not increase over time. Mean hemoglobin levels and 95% confidence intervals were maintained within the target range (10.0-12.0 g/dl) over 52 weeks in both studies. The long-term safety and efficacy of enarodustat were confirmed in Japanese anemic patients with chronic kidney disease.

SUBMITTER: Akizawa T

PROVIDER: S-EPMC9290460 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies.

Akizawa Tadao T Nangaku Masaomi M Yamaguchi Takuhiro T Koretomo Ryosuke R Maeda Kazuo K Yamada Osamu O Hirakata Hideki H

Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 20210902 2

Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease. Two open-label, uncontrolled phase 3 studies evaluated the 52-week safety and efficacy of enarodustat in Japanese anemic patients with chronic kidney disease not on dialysis (n = 132) [SYMPHONY ND-Long study] or on maintenance hemodialysis (n = 136) [SYMPHONY HD-Long study]. The most frequent adverse events were viral upper respiratory tract infection (2 ...[more]

PMID: 34390314

Similar Datasets

Project description:BackgroundPatients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) experience many distressing symptoms. One frequently reported symptom is insomnia. There are unique issues about HD treatments and schedules that disrupt regular sleep/wake routines and possibly contribute to the high severity of insomnia. Despite evidence for broad-ranging health effects of insomnia, very few clinical trials have tested the efficacy of treatments for HD patients. Cognitive-behavioral therapy for insomnia (CBT-I) is a recommended first-line therapy but largely inaccessible to HD patients in the United States, partly because they commit considerable amounts of time to thrice-weekly dialysis treatments. Another important reason could be the logistical and reimbursement challenges associated with providing behavioral health care at the dialysis center. CBT-I delivered by telehealth can overcome barriers to access, but its efficacy has never been rigorously tested for these patients. Pharmacotherapy is the most widely used treatment for insomnia; however, some drugs presently used are unsafe as they are associated with a higher risk for death for HD patients (benzodiazepines and zolpidem-like drugs). The efficacy and safety of other medications (trazodone) for the treatment of insomnia has never been tested for patients treated with HD.MethodsThis trial tests the short- and long-term comparative effectiveness of 6-week treatment with telehealth CBT-I, trazodone, or medication placebo. This will be accomplished with a randomized controlled trial (RCT) in which 126 participants treated with HD in community-based dialysis facilities with chronic insomnia will be assigned 1:1:1 to telehealth CBT-I, trazodone, or medication placebo, respectively; short-term effectiveness of each treatment arm will be determined at the end of 6-weeks of treatment and long-term effectiveness at 25-weeks. The primary and secondary patient-reported outcomes will be assessed with computer-based telephone interviewing by research scientists blinded to treatment assignment; additional secondary outcomes will be assessed by participant interview and actigraphy.DiscussionThis clinical RCT will provide the first evidence for the comparative effectiveness of two distinct approaches for treating chronic insomnia and other patient-reported outcomes for patients receiving maintenance HD.Trial registrationNCT03534284 May 23, 2018. SLEEP-HD Protocol Version: 1.3.4 (7/22/2020).

Project description:BackgroundPeople receiving in-center hemodialysis (HD) have prioritized the need for more individualized health information and better communication with nephrologists. The most common setting for patient-nephrologist interactions is during the HD treatment, which is a time pressured setting that lacks privacy.ObjectiveTo facilitate effective communication in the hemodialysis (HD) unit, we evaluated the usability of a web application (web app) from both the patient and physician perspective. The main aim of the web app was to support patients in prioritizing their dialysis concerns outside of the clinical HD encounter.DesignMixed method, parallel arm, multi-site, pilot randomized controlled trial.SettingTwo outpatient Canadian HD centers.ParticipantsAdult patients receiving in-center HD and their attending nephrologists.MethodsPatients were randomized to either a web application or an active control (paper form) for logging concerns to be addressed at weekly encounters with the nephrologist over 8 weeks. Topics included: HD treatment, symptoms, modality, and medications. The primary outcome was usability, defined as effectiveness (engagement with the tool, frequency of submitted concerns, whether the concern was satisfactorily addressed) and satisfaction with the tool using a priori thresholds and explored in interviews with patients and nephrologists.Results77 patients (30 women, median age 61, interquartile range [53,67], median 2 years [1,4] on dialysis) and 19 nephrologists (4 women, median age 46 [36,65]) were enrolled. Patient use of a digital device at baseline was low (20%). Engagement with the tool was 70% (web app) and 100% (paper) with a lower proportion of patients in the web app group submitting at least one concern over 8 weeks compared to the paper form group: 56.7% vs 87.9%. Weekly concerns were satisfactorily addressed in both groups and ≥70% of patients would continue to use the tools. For patients, both tools promoted preparation and participation in the encounter; however, only the web app facilitated greater privacy in relaying concerns. For most nephrologists, the tools were disruptive to their workflow and were perceived as unnecessary given existing processes and familiarity with patients. For future versions of the app, patients suggested more features to facilitate self-management and nephrologists suggested integration with health databases and multidisciplinary teams.LimitationsTertiary setting may limit generalizability.ConclusionsBoth tools promoted fundamental components of self-management; however, patients in the paper form group submitted concerns more often and this tool was easier to remember to use. Although modifications would likely enhance web app usability, successful future adoption is limited by physician acceptance.Trial registration ClinicalTrials.gov NCT03605875.

Project description:BackgroundIn contrast to the general population, higher body mass index (BMI) is associated with greater survival in patients receiving hemodialysis (HD; "obesity paradox"). We hypothesized that this paradoxical association between BMI and death may be modified by age and dialysis vintage.Study designRetrospective observational study using a large HD patient cohort.Setting & participants123,383 maintenance HD patients treated in DaVita dialysis clinics between July 1, 2001, and June 30, 2006, with follow-up through September 30, 2009.PredictorsAge, dialysis vintage, and time-averaged BMI. Time-averaged BMI was divided into 6 subgroups; <18.5, 18.5-<23.0, 23.0-<25.0, 25.0-<30.0, 30.0-<35.0, and ≥35.0kg/m(2). BMI category of 23-<25kg/m(2) was used as the reference category.OutcomesAll-cause, cardiovascular, and infection-related mortality.ResultsMean BMI of study participants was 27±7kg/m(2). Time-averaged BMI was <18.5 and ≥35kg/m(2) in 5% and 11% of patients, respectively. With progressively higher time-averaged BMI, there was progressively lower all-cause, cardiovascular, and infection-related mortality in patients younger than 65 years. In those 65 years or older, even though overweight/obese patients had lower mortality compared with underweight/normal-weight patients, sequential increases in time-averaged BMI > 25kg/m(2) added no additional benefit. Based on dialysis vintage, incident HD patients had greater all-cause and cardiovascular survival benefit with a higher time-averaged BMI compared with the longer term HD patients.LimitationsCausality cannot be determined, and residual confounding cannot be excluded given the observational study design.ConclusionsHigher BMI is associated with lower death risk across all age and dialysis vintage groups. This benefit is more pronounced in incident HD patients and those younger than 65 years. Given the robustness of the survival advantage of higher BMI, examining interventions to maintain or even increase dry weight in HD patients irrespective of age and vintage are warranted.

Project description:IntroductionRenal anemia is a common complication among patients with non-dialysis chronic kidney disease (ND-CKD), and there remains an unmet need for more efficient and convenient daily oral medications to improve patient outcomes. This study aimed to evaluate the efficacy and safety of enarodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, in treating anemia for ND-CKD patients.MethodsThis phase 3 study was conducted at 48 centers across China, enrolling 156 ND-CKD patients. Participants were randomly randomized in a 2:1 ratio to receive either enarodustat or placebo for an initial 8-week double-blind period, followed by a 16-week open-label period during which all patients received enarodustat.ResultsThe primary endpoint was the mean change in hemoglobin (Hb) levels from baseline to the average level during weeks 7-9. Secondary endpoints focused on Hb concentration or treatment pattern, while exploratory endpoints assessed iron metabolism-related parameters. The mean (±SD) change in Hb levels from baseline to weeks 7-9 was 15.99 (±9.46) g/L in the enarodustat group, compared to -0.14 (±8.08) g/L in the placebo group, resulting in a mean difference of 16.00 (±1.54) g/L (p < 0.001). During weeks 7-9, 85.3% of patients in the enarodustat group achieved Hb levels ≥100 g/L with 86.0% maintaining this level during weeks 21-25. In the first 4 weeks, the Hb increased by 11.82 (±9.56) g/L in the enarodustat group. By week 9, the mean change in hepcidin level was -42.94 (±37.56) ng/mL in the enarodustat group, compared to +4.58 (±33.34) ng/mL in the placebo group. Enarodustat also improved other iron-related parameters and reduced the need for iron supplements. The safety profile of enarodustat was well tolerable with adverse events comparable to those of the placebo.ConclusionEnarodustat effectively corrected renal anemia with a manageable safety profile. Its once-daily oral administration offers convenience that may enhance the adherence. Enarodustat shows the potential as a promising therapy for anemic patients with ND-CKD.

Dataset Information

Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies.

Publications

Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets