Evidence map›Paper›PMID 36565721›Full record

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

Analysis of on-treatment cancer safety events with daprodustat versus conventional erythropoiesis-stimulating agents-post hoc analyses of the ASCEND-ND and ASCEND-D trials.

Ajay K Singh, Finnian R McCausland, Brian L Claggett, Christoph Wanner, Andrzej Wiecek, Michael B Atkins, Kevin Carroll, Vlado Perkovic, John J V McMurray, Janet Wittes and 8 more

2 registry-linked trialsOpen access · greenAbstract read
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. It is linked to 2 registered trials, which are not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 15% 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.

NCT02876835 phase3completednot on this map

A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Darbepoetin Alfa

TypeinterventionalSponsorGlaxoSmithKlineRan2016 to 2021Enrolled3,872ConditionsAnaemiaArmsDaprodustat, Darbepoetin alfa, Placebo, Iron Therapy
NCT02879305 phase3completednot on this map

A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Recombinant Human Erythropoietin, Following a Switch From Erythropoietin-stimulating Agents

TypeinterventionalSponsorGlaxoSmithKlineRan2016 to 2020Enrolled2,964ConditionsAnaemia, Aspergillosis, Allergic BronchopulmonaryArmsDaprodustat, rhEPO, Placebo, Iron therapy
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP).Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
  3. Review
  4. Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a clinical practice document by the European Renal Best Practice board of the European Renal Association.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Review
  5. Article
  6. Article
  7. Review
  8. Article
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

18 authors at 9 institutions in 5 countries.

Ajay K SinghRenal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Finnian R McCauslandRenal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-0299-0533
Brian L ClaggettHarvard Medical School, Boston, MA, USA.
Christoph WannerUniversity Hospital of Würzburg, Würzburg, Germany.ORCID 0000-0001-9507-5301
Andrzej WiecekDepartment of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland.
Michael B AtkinsGeorgetown-Lombardi Comprehensive Cancer Center, Washington DC, USA.
Kevin CarrollKJC Statistics, Cheshire, UK.
Vlado PerkovicFaculty of Medicine and Health, University of New South Wales, Sydney, Australia.
John J V McMurrayInstitute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, Glasgow, University of Glasgow, UK.
Janet WittesWittes LLC, Washington DC, USA.ORCID 0000-0002-6625-835X
Steven SnapinnSeattle-Quilcene Biostatistics LLC, Seattle, WA, USA.
Allison BlackorbyGlaxoSmithKline, Collegeville, PA, USA.
Amy MeadowcroftGlaxoSmithKline, Collegeville, PA, USA.
Tara BarkerGlaxoSmithKline, Collegeville, PA, USA.
Tara DiMinoGlaxoSmithKline, Collegeville, PA, USA.
Stephen MallettGlaxoSmithKline, Brentford, London, UK.
Alexander R CobitzGlaxoSmithKline, Collegeville, PA, USA.
Scott D SolomonHarvard Medical School, Boston, MA, USA.
GlaxoSmithKline (United States) · USBrigham and Women's Hospital · USCheshire West and Chester · GBGeorgetown Lombardi Comprehensive Cancer CenterGlaxoSmithKline (United Kingdom) · GBMedical University of Silesia · PLUniversitätsklinikum Würzburg · DEUniversity of Glasgow · GBUNSW Sydney · AU

Funding

Angiotensin-Neprilysin Inhibition in Hemodialysis InitiationR01DK129749 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI MCCAUSLAND, FINNIAN R · 2022 to 2024
$1.1M
Patient Symptoms on Hemodialysis-Timing, Variability and CausesR03DK122240 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI MCCAUSLAND, FINNIAN R · 2019 to 2020
$179k
NIDDK NIH HHS R01 DK129749NIDDK NIH HHS R03 DK122240
6 · The paper itself

Abstract

backgroundThe prespecified on-treatment analysis of ASCEND-ND (NCT02876835) raised concerns about a higher relative risk of cancer-related adverse events (AEs) with daprodustat vs darbepoetin in patients with anaemia of CKD. This concern was not observed in dialysis patients in ASCEND-D (NCT02879305).

methodsASCEND-ND randomized 3872 patients to daprodustat or darbepoetin. ASCEND-D randomized 2964 patients to daprodustat or conventional erythropoiesis-stimulating agents (ESAs). In both studies ESA comparators used different dosing intervals (3/week, 1/week, every 2 or every 4 weeks). The prespecified on-treatment approach examined relative risks for cancer AEs up to the last dose date + 1 day. In these analyses, owing to different dosing intervals between arms, Cox models were used to estimate the daprodustat effect by various follow-up periods (censoring at last dose date, last dose date + dosing intervals, or end of study).

resultsIn ASCEND-ND, the safety of daprodustat vs darbepoetin on cancer-related AEs depended on the duration of follow-up after last dose date: hazard ratio (HR) 1.04 [95% confidence interval (CI) 0.77, 1.40] at end of study [HR 1.12 (95% CI 0.81, 1.56) for last dose date + dosing interval; HR 1.50 (95% CI 1.04, 2.15) for last dose date + 1 day]. In ASCEND-D, no excess risk of cancer-related AEs was observed with any model examined.

conclusionsPrespecified on-treatment analyses for cancer-related AEs appeared to result in biased risk estimates in ASCEND-ND by preferentially under-counting events from patients assigned to darbepoetin. Analyses accounting for longer darbepoetin dosing intervals, or extending follow-up, resulted in attenuation of effect estimates towards neutrality, similar to ASCEND-D, where ESA comparator dosing intervals are closer to daprodustat.

trial registrationThe ASCEND-ND trial is registered with ClinicalTrials.gov (NCT02876835); the ASCEND-D trial is registered with ClinicalTrials.gov (NCT02879305).

Indexed as

ErythropoietinHematinicsNeoplasmsRenal Insufficiency, ChronicBarbituratesDarbepoetin alfaErythropoiesisGlycineHemoglobinsHumansRenal DialysisBarbituratesDarbepoetin alfaErythropoietinGlycineGSK1278863HematinicsHemoglobinsanaemiacancerchronic kidney diseaseprolyl-hydroxylase inhibitorsafety

Identifiers

PMID36565721
PMCPMC10387380
OpenAlexW4312140241

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

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 Socratic graph.