Evidence map›Paper›PMID 29142983›Full record

ArticleKidney international reports2017

Efficacy and Safety of Sparsentan Compared With Irbesartan in Patients With Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET).

Radko Komers, Debbie S Gipson, Peter Nelson, Sharon Adler, Tarak Srivastava, Vimal K Derebail, Kevin E Meyers, Pablo Pergola, Meghan E MacNally, Jennifer L Hunt and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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

27 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Interventions for focal segmental glomerulosclerosis in adults.The Cochrane database of systematic reviews · 2022
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  15. Targeting tissue-resident memory CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2022
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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

12 authors.

Radko KomersRetrophin Inc, Cambridge, Massachusetts, USA.
Debbie S GipsonDivision of Pediatric Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
Peter NelsonDivision of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, USA.
Sharon AdlerDivision of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California, USA.
Tarak SrivastavaChildren's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
Vimal K DerebailDivision of Nephrology and Hypertension, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Kevin E MeyersDivision of Nephrology, The Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Pablo PergolaRenal Associates PA, San Antonio, Texas, USA.
Meghan E MacNallyRetrophin Inc, Cambridge, Massachusetts, USA.
Jennifer L HuntRetrophin Inc, Cambridge, Massachusetts, USA.
Alvin ShihRetrophin Inc, Cambridge, Massachusetts, USA.
Howard TrachtmanDivision of Pediatric Nephrology, NYU School of Medicine, Langone Medical Center, New York, New York, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPrimary focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and end-stage renal disease. There are no US Food and Drug Administration-approved therapies for FSGS, and treatment often fails to reduce proteinuria. Endothelin is an important factor in the pathophysiology of podocyte disorders, including FSGS. Sparsentan is a first-in-class, orally active, dual-acting angiotensin receptor blocker (ARB) and highly selective endothelin Type A receptor antagonist. This study is designed to evaluate whether sparsentan lowers proteinuria compared with an ARB alone and has a favorable safety profile in patients with FSGS.

methodsDUET is a phase 2, randomized, active-control, dose-escalation study with an 8-week, fixed-dose, double-blind period followed by 136 weeks of open-label sparsentan treatment. Patients aged 8 to 75 years with primary FSGS will be randomized to treatment with sparsentan or irbesartan for 8 weeks.

resultsThe primary efficacy objective is to test the hypothesis that sparsentan over the dose range (200 mg, 400 mg, or 800 mg daily) is superior to irbesartan (300 mg daily) in decreasing the urinary protein-to-creatinine ratio (UPC) from baseline to 8 weeks postrandomization. As secondary objectives, the trial will evaluate the proportion of patients who achieve prespecified targets of UPC reduction, changes in laboratory and quality-of-life indices, and detailed safety analysis. Analyses will be conducted at the end of the double-blind (week 8) and open-label (week 144) periods. DISCUSSION: This study will provide important evidence on whether dual ARB and endothelin blockade may be an effective therapeutic strategy for FSGS and may provide the rationale for next-phase trials.

Indexed as

endothelin receptor antagonistfocal segmental glomerulosclerosisirbesartannephrotic syndromeproteinuriasparsentan

Identifiers

PMID29142983
PMCPMC5678638

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Registered trials

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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.