Evidence map›Paper›PMID 33338269›Full record

Trial reportClinical pharmacology and therapeutics2021

Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease.

Jeroen V Koomen, Jasper Stevens, George Bakris, Ricardo Correa-Rotter, Fan Fan Hou, Dalane W Kitzman, Donald E Kohan, Hirofumi Makino, John J V McMurray, Hans-Henrik Parving and 4 more

Open access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

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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 12 institutions in 9 countries.

Jeroen V KoomenDepartment Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jasper StevensDepartment Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
George BakrisAmerican Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA.
Ricardo Correa-RotterNational Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico.
Fan Fan HouDivision of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China.
Dalane W KitzmanWake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Donald E KohanDivision of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Hirofumi MakinoOkayama University, Okayama, Japan.
John J V McMurrayBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Hans-Henrik ParvingDepartment of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Vlado PerkovicGeorge Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia.
Sheldon W TobeDivision of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto and the Northern Ontario School of Medicine, Toronto, Ontario, Canada.
Dick de ZeeuwDepartment Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hiddo J L HeerspinkDepartment Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
The George Institute for Global Health · AUUniversity of Groningen · NLAarhus University · DKBritish Heart Foundation · GBInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXNanfang Hospital · CNOkayama University · JPSunnybrook Health Science Centre · CAUniversity Medical Center Groningen · NLUniversity of Chicago · USUniversity of Utah · USWake Forest University · US

Funding

AbbvieNetherlands Organisation for Scientific Research 917.15.306Novo Nordisk Foundation OC0013659
6 · The paper itself

Abstract

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.

Indexed as

AgedArea Under CurveAtrasentanDiabetes Mellitus, Type 2Diabetic NephropathiesDouble-Blind MethodEndothelin Receptor AntagonistsFemaleGlomerular Filtration RateHeart FailureHumansKidney Failure, ChronicMaleMiddle AgedTreatment OutcomeAtrasentanEndothelin Receptor Antagonists

Identifiers

PMID33338269
PMCPMC8246733
OpenAlexW3111851331

What OpenQuestion holds

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LicenceCC BY-NC
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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.