Evidence map›Paper›PMID 36002026›Full record

ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2023

Randomized, double-blind, placebo-controlled phase 3 study of bardoxolone methyl in patients with diabetic kidney disease: design and baseline characteristics of the AYAME study.

Masaomi Nangaku, Hirotaka Takama, Tomohiro Ichikawa, Kazuya Mukai, Masahiro Kojima, Yusuke Suzuki, Hirotaka Watada, Takashi Wada, Kohjiro Ueki, Ichiei Narita and 4 more

Open access · hybridAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 41 citations in OpenAlex.

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  19. NRF2 in kidney physiology and disease.Physiological reports · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 9 institutions in 1 country.

Masaomi NangakuDivision of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Hirotaka TakamaResearch & Development Division, Kyowa Kirin, Tokyo, Japan.
Tomohiro IchikawaResearch & Development Division, Kyowa Kirin, Tokyo, Japan.
Kazuya MukaiResearch & Development Division, Kyowa Kirin, Tokyo, Japan.
Masahiro KojimaResearch & Development Division, Kyowa Kirin, Tokyo, Japan.
Yusuke SuzukiDepartment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Hirotaka WatadaDepartment of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.ORCID 0000-0001-5961-1816
Takashi WadaDepartment of Nephrology and Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan.ORCID 0000-0002-0123-3645
Kohjiro UekiDepartment of Diabetes, Endocrinology, and Metabolism, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan.
Ichiei NaritaDivision of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Naoki KashiharaDepartment of Nephrology and Hypertension, Kawasaki Medical School, Okayama, Japan.
Takashi KadowakiToranomon Hospital, Tokyo, Japan.
Hiroki HaseAoba Hospital, Tokyo, Japan.
Tadao AkizawaDivision of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
Kyowa Kirin (Japan) · JPJuntendo University · JPKanazawa University · JPKawasaki Medical School · JPNational Center for Global Health and Medicine · JPNiigata University · JPShowa University · JPThe University of Tokyo · JPToranomon Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD), but currently available treatments do not improve kidney function or prevent the initiation of dialysis/kidney replacement therapy. A previous study demonstrated that bardoxolone methyl improves the estimated glomerular filtration rate (eGFR), but the study was prematurely terminated because of an imbalance in heart failure between treatment groups. The subsequent phase 2 TSUBAKI study demonstrated no incidence of heart failure and an improved eGFR and GFR as determined by inulin clearance in DKD patients.

methodsThis randomized, double-blind, placebo-controlled multicentre phase 3 study was designed to assess the efficacy and safety of bardoxolone methyl in DKD patients with an eGFR ≥15.0-<60.0 ml/min/1.73 m2 and a urinary albumin:creatinine ratio (UACR) ≤3500 mg/g but without risk factors for heart failure. The primary endpoint is the time to onset of a ≥30% decrease in the eGFR or ESKD. Randomized patients (1:1) have been under treatment with once-daily oral bardoxolone methyl (5, 10 or 15 mg by intrapatient dose adjustment) or placebo for at least 3 years.

resultsThe mean age of the 1013 patients is 65.9 years, 21.5% are female, the mean eGFR is 37.84 ml/min/1.73 m2 and the median UACR is 351.80 mg/g.

conclusionsAppropriate patients are enrolled in this study. This study will investigate the long-term efficacy and safety of bardoxolone methyl in DKD patients covering a wider range of eGFR (≥15.0-<60.0 ml/min/1.73 m2) and albuminuria (≤3500 mg/g) compared with previous studies.

Indexed as

Diabetes Mellitus, Type 2Diabetic NephropathiesHeart FailureKidney Failure, ChronicRenal Insufficiency, ChronicAgedAlbuminuriaClinical Trials, Phase III as TopicDouble-Blind MethodFemaleGlomerular Filtration RateHumansMaleMulticenter Studies as TopicOleanolic AcidRandomized Controlled Trials as Topicbardoxolone methylOleanolic Acidbardoxolone methyldiabetic kidney diseaseglomerular filtration rateheart failuresurrogate renal endpoint

Identifiers

PMID36002026
PMCPMC10157761
OpenAlexW4293104252

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.