Evidence map›Paper›PMID 31387097›Full record

Trial reportNephron2019

Iron Regulation by Molidustat, a Daily Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, in Patients with Chronic Kidney Disease.

Tadao Akizawa, Iain C Macdougall, Jeffrey S Berns, Hiroyasu Yamamoto, Megumi Taguchi, Kazuma Iekushi, Thomas Bernhardt

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nephron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 3 pooled it
3.6field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 3 syntheses or guidelines pooled it, 31 citations in OpenAlex.

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  17. The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Article
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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

7 authors at 6 institutions in 4 countries.

Tadao AkizawaDivision of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan, akizawa@med.showa-u.ac.jp.
Iain C MacdougallDepartment of Renal Medicine, King's College Hospital, London, United Kingdom.
Jeffrey S BernsPerelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hiroyasu YamamotoDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Megumi TaguchiBayer Yakuhin Ltd., Osaka, Japan.
Kazuma IekushiBayer Yakuhin Ltd., Osaka, Japan.
Thomas BernhardtBayer Pharma AG, Berlin, Germany.
Bayer (Japan) · JPBayer (Germany) · DEJikei University School of Medicine · JPKing's College Hospital · GBPennsylvania Hospital · USShowa University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

aimsThe current treatment for anemia associated with chronic kidney disease (CKD) includes the administration of erythropoiesis stimulating agents (ESAs) combined with iron supplementation. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has potential to treat anemia associated with CKD through increased erythropoietin production and improved iron availability. Here, we report the effect of molidustat on iron metabolism.

methodParameters of iron metabolism were monitored in three 16-week, randomized, controlled, phase 2 studies assessing the safety and efficacy of molidustat in the treatment of anemia associated with CKD in different populations: treatment-naïve and previously ESA-treated patients not on dialysis, and previously ESA-treated patients on hemodialysis. Iron supplementation was left at the discretion of the investigator.

resultsIn treatment-naïve patients not on dialysis, transferrin saturation (TSAT), hepcidin, ferritin, and iron concentrations decreased with molidustat, whereas total iron binding capacity (TIBC) increased. Similar results were observed in previously ESA-treated patients not on dialysis, although changes in those parameters were larger in treatment-naïve than in previously ESA-treated patients. In previously ESA-treated patients receiving hemodialysis, hepcidin concentration and TIBC remained stable with molidustat, whereas TSAT and ferritin and iron concentrations increased. Generally, similar trends were observed in secondary analyses of subgroups of patients not receiving iron supplementation.

conclusionsMolidustat is a potential alternative to standard treatment of anemia associated with CKD, with a different mechanism of action. In patients not receiving dialysis, molidustat increases iron availability. In patients receiving hemodialysis, further investigation is required to understand fully the mechanisms underlying iron mobilization associated with molidustat.

Indexed as

Administration, OralAgedAged, 80 and overAnemiaBasic Helix-Loop-Helix ProteinsDouble-Blind MethodEndothelial PAS Domain-Containing Protein 1FemaleHematinicsHemoglobinsHepcidinsHumansHypoxia-Inducible Factor 1, alpha SubunitIronMaleMiddle AgedBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1HematinicsHemoglobinsHepcidinsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIronmolidustatProlyl-Hydroxylase InhibitorsPyrazolesTriazolesAnemiaChronic kidney diseaseHypoxia-inducible factor prolyl hydroxylase inhibitorIron metabolismMolidustat

Identifiers

PMID31387097
PMCPMC6979436
OpenAlexW2966671945

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.