Trial reportClinical journal of the American Society of Nephrology : CJASN2014
Predictors of congestive heart failure after treatment with an endothelin receptor antagonist.
Trial report in Clinical journal of the American Society of Nephrology : CJASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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.
Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Effects of combined treatment with zibotentan and dapagliflozin compared to dapagliflozin alone in patients with diabetic and non-diabetic chronic kidney disease.Diabetes, obesity & metabolism · 2025Trial
- Effects of Zibotentan Alone and in Combination with Dapagliflozin on Fluid Retention in Patients with CKD.Journal of the American Society of Nephrology : JASN · 2024Trial
- Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers.European journal of preventive cardiology · 2016Trial
- The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy: A Randomized Double-Blind Placebo-Controlled Clinical Trial.Journal of the American Society of Nephrology : JASN · 2025Article
- Efficacy and safety of endothelin A receptor antagonists in IgA nephropathy: a systematic review and meta-analysis.Clinical kidney journal · 2025Article
- Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Endothelin Inhibitors in Chronic Kidney Disease: New Treatment Prospects.Journal of clinical medicine · 2024Review
- Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Pharmacological management of youth with type 2 diabetes and diabetic kidney disease: a comprehensive review of current treatments and future directions.Expert opinion on pharmacotherapy · 2023Review
- Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond?Nephrology (Carlton, Vic.) · 2023Review
- Treatment and practical considerations of diabetic kidney disease.Frontiers in medicine · 2023Review
- Endothelin-targeted new treatments for proteinuric and inflammatory glomerular diseases: focus on the added value to anti-renin-angiotensin system inhibition.Pediatric nephrology (Berlin, Germany) · 2021Review
- The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease.Kidney diseases (Basel, Switzerland) · 2020Review
- An integrative systems biology approach for precision medicine in diabetic kidney disease.Diabetes, obesity & metabolism · 2018Review
- Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial: A clinical trial design novel to diabetic nephropathy.Diabetes, obesity & metabolism · 2018Article
- Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets.Journal of diabetes research · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death (ASCEND) trial tested the renoprotective effect of the endothelin receptor antagonist avosentan in patients with diabetes and nephropathy, but the study was terminated due to an excess of congestive heart failure (CHF) events in the avosentan arms, likely due to fluid retention. The aim of this study was to identify risk markers of CHF after treatment with avosentan. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a post hoc analysis of the ASCEND trial (N=1392 participants), we assessed which baseline characteristics predicted CHF risk during avosentan treatment. Furthermore, postrandomization changes between baseline and the first available measurement of body weight and hemoglobin were examined as potential clinical indicators of fluid retention for their relationship with CHF development.
resultsRelative to placebo, avosentan increased CHF risk (hazard ratio, 2.76; 95% confidence interval, 1.68 to 4.54). The avosentan-related CHF risk was higher with lower baseline cholesterol levels (P interaction=0.003) and concomitant statin use (P interaction=0.06), whereas it was lower with a lower estimated GFR (P interaction=0.04). Patients allocated to avosentan had a median body weight increase of 0.6 kg (interquartile range, 0.0 to 2.0 kg) and a median hemoglobin decrease of 1.4 g/dl (interquartile range, -2.1 to -0.7 g/dl) at the first postrandomization measurement. The body weight increase induced by avosentan was associated with CHF development (P interaction=0.04), whereas hemoglobin decrease was not (P interaction=0.64). The increase in body weight was particularly pronounced in patients with a cardiovascular disease history and in patients using statins.
conclusionsIn avosentan-treated patients, body weight increase, but not hemoglobin decrease, was associated with CHF development, indicating that close body weight monitoring could provide an early signal of CHF development in future trials with endothelin receptor antagonists.
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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 OpenQuestion graph.