Evidence map›Paper›PMID 26494831›Full record

Trial reportJournal of the American Society of Nephrology : JASN2016

Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.

Louis Holdstock, Amy M Meadowcroft, Rayma Maier, Brendan M Johnson, Delyth Jones, Anjay Rastogi, Steven Zeig, John J Lepore, Alexander R Cobitz

Abstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 12 pooled it
13.3field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 12 syntheses or guidelines pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Guideline
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Trial
  14. Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.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 · 2021
    Trial
  15. Trial
  16. Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Trial
  17. Trial
  18. Article
  19. Review
  20. Article

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 3 countries.

Louis HoldstockMetabolic Pathways and Cardiovascular Therapeutic Area and Louis.2.holdstock@gsk.com.
Amy M MeadowcroftMetabolic Pathways and Cardiovascular Therapeutic Area and.
Rayma MaierClinical Statistics, GlaxoSmithKline, Stockley Park, London, United Kingdom;
Brendan M JohnsonClinical Pharmacology Modeling and Simulation, GlaxoSmithKline, Research Triangle Park, North Carolina;
Delyth JonesClinical Statistics, GlaxoSmithKline, Stockley Park, London, United Kingdom;
Anjay RastogiDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California;
Steven ZeigPines Clinical Research, Pembroke Pines, Florida; and.
John J LeporeMetabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, Pennsylvania.
Alexander R CobitzMetabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, Pennsylvania.
GlaxoSmithKline (United Kingdom) · GBPathways Behavioral Services · USResearch Triangle Park Foundation · USGlaxoSmithKline (United States) · USUniversity of California, Los Angeles · USUniversity of North Carolina at Pembroke · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia-inducible factor prolyl hydroxylase inhibitors stabilize levels of hypoxia-inducible factor that upregulate transcription of multiple genes associated with the response to hypoxia, including production of erythropoietin. We conducted two phase 2a studies to explore the relationship between the dose of the hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 and hemoglobin response in patients with anemia of CKD (baseline hemoglobin 8.5-11.0 g/dl) not undergoing dialysis and not receiving recombinant human erythropoietin (nondialysis study) and in patients with anemia of CKD (baseline hemoglobin 9.5-12.0 g/dl) on hemodialysis and being treated with stable doses of recombinant human erythropoietin (hemodialysis study). Participants were randomized 1:1:1:1 to a once-daily oral dose of GSK1278863 (0.5 mg, 2 mg, or 5 mg) or control (placebo for the nondialysis study; continuing on recombinant human erythropoietin for the hemodialysis study) for 4 weeks, with a 2-week follow-up. In the nondialysis study, GSK1278863 produced dose-dependent effects on hemoglobin, with the highest dose resulting in a mean increase of 1 g/dl at week 4. In the hemodialysis study, treatment with GSK1278863 in the 5-mg arm maintained mean hemoglobin concentrations after the switch from recombinant human erythropoietin, whereas mean hemoglobin decreased in the lower-dose arms. In both studies, the effects on hemoglobin occurred with elevations in endogenous erythropoietin within the range usually observed in the respective populations and markedly lower than those in the recombinant human erythropoietin control arm in the hemodialysis study, and without clinically significant elevations in plasma vascular endothelial growth factor concentrations. GSK1278863 was generally safe and well tolerated at the doses and duration studied. GSK1278863 may prove an effective alternative for managing anemia of CKD.

Indexed as

AgedAnemiaBarbituratesErythropoietinFemaleGlycineHemoglobinsHumansHypoxia-Inducible Factor-Proline DioxygenasesMaleMiddle AgedRenal DialysisRenal Insufficiency, ChronicSingle-Blind MethodTime FactorsBarbituratesErythropoietinGlycineGSK1278863HemoglobinsHypoxia-Inducible Factor-Proline DioxygenasesanemiaCKDerythropoietin

Identifiers

PMID26494831
PMCPMC4814173
OpenAlexW2206481924

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.