PMID- 33883252
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230203
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 32
IP  - 7
DP  - 2021 Jul
TI  - Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in 
      Japanese Patients with Nondialysis-Dependent CKD.
PG  - 1779-1790
LID - 10.1681/ASN.2020091311 [doi]
AB  - BACKGROUND: Standard care for treating anemia in patients with CKD includes use 
      of erythropoiesis-stimulating agents, which sometimes involves increased risks of 
      cardiovascular morbidity and mortality. Previous studies in patients with anemia 
      and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin 
      levels with use of vadadustat, an oral hypoxia-inducible factor prolyl 
      hydroxylase inhibitor, compared with placebo. METHODS: In this phase 3, 
      open-label, active-controlled noninferiority trial, we randomized 304 Japanese 
      adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users 
      and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. 
      The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety 
      data included adverse events (AEs) and serious AEs. RESULTS: A total of 151 
      participants received vadadustat and 153 received darbepoetin alfa. Least squares 
      mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence 
      interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 
      to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within 
      the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit 
      for the difference between groups (-0.50 g/dl) was above the predefined 
      noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to 
      darbepoetin alfa. Similar proportions of patients in each group reported AEs and 
      serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, 
      diarrhea, and constipation. CONCLUSIONS: In Japanese patients with NDD-CKD, 
      vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in 
      terms of average hemoglobin, and was generally well tolerated. These results 
      suggest that vadadustat may be a potential treatment for anemia in this patient 
      population.
CI  - Copyright (c) 2021 by the American Society of Nephrology.
FAU - Nangaku, Masaomi
AU  - Nangaku M
AD  - Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
FAU - Kondo, Kazuoki
AU  - Kondo K
AD  - Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Kokado, Yoshimasa
AU  - Kokado Y
AD  - Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Ueta, Kiichiro
AU  - Ueta K
AD  - Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Kaneko, Genki
AU  - Kaneko G
AD  - Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Tandai, Tsubasa
AU  - Tandai T
AD  - Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Kawaguchi, Yutaka
AU  - Kawaguchi Y
AD  - Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Komatsu, Yasuhiro
AU  - Komatsu Y
AD  - Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.
LA  - eng
PT  - Journal Article
DEP - 20210421
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
SB  - IM
PMC - PMC8425651
OTO - NOTNLM
OT  - HIF prolyl hydroxylase inhibitor
OT  - Japan
OT  - anemia
OT  - erythropoiesis
OT  - nondialysis-dependent CKD
OT  - vadadustat
EDAT- 2021/04/23 06:00
MHDA- 2021/04/23 06:01
PMCR- 2022/07/01
CRDT- 2021/04/22 06:04
PHST- 2020/09/14 00:00 [received]
PHST- 2021/02/19 00:00 [accepted]
PHST- 2021/04/23 06:00 [pubmed]
PHST- 2021/04/23 06:01 [medline]
PHST- 2021/04/22 06:04 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - 00001751-202107000-00021 [pii]
AID - 2020091311 [pii]
AID - 10.1681/ASN.2020091311 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2021 Jul;32(7):1779-1790. doi: 10.1681/ASN.2020091311. Epub 
      2021 Apr 21.