Trial reportEuropean journal of preventive cardiology2016
Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers.
Trial report in European journal of preventive cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 35 citations in OpenAlex.
- Prediction and validation of exenatide risk marker effects on progression of renal disease: Insights from EXSCEL.Diabetes, obesity & metabolism · 2020Trial
- Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers.Diabetes, obesity & metabolism · 2016Trial
- In silico prediction of optimal multifactorial intervention in chronic kidney disease.Journal of translational medicine · 2025Article
- Efficacy and safety of endothelin A receptor antagonists in IgA nephropathy: a systematic review and meta-analysis.Clinical kidney journal · 2025Article
- Targeting endothelin signaling in podocyte injury and diabetic nephropathy-diabetic kidney disease.Journal of nephrology · 2025Review
- Prediction of the Effects of Liraglutide on Kidney and Cardiovascular Outcomes Based on Short-Term Changes in Multiple Risk Markers.Frontiers in pharmacology · 2022Article
- Endothelin Receptor Antagonists as a Potential Treatment of Diabetic Nephropathy: A Systematic Review.Cureus · 2021Review
- Endothelin receptors in renal interstitial cells do not contribute to the development of fibrosis during experimental kidney disease.Pflugers Archiv : European journal of physiology · 2021Article
- Precision medicine approaches for diabetic kidney disease: opportunities and challenges.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Review
- Prediction of the Effects of Empagliflozin on Cardiovascular and Kidney Outcomes Based on Short-Term Changes in Multiple Risk Markers.Frontiers in pharmacology · 2021Article
- A novel drug response score more accurately predicts renoprotective drug effects than existing renal risk scores.Therapeutic advances in endocrinology and metabolism · 2021Article
- A Review of the Dose Justification of Phase 3 Trials to Regulatory Authorities for Drugs Intended for the Treatment of Type 2 Diabetes in Europe.Frontiers in pharmacology · 2021Article
- Time for clinical decision support systems tailoring individual patient therapy to improve renal and cardiovascular outcomes in diabetes and nephropathy.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Review
- The SONAR study-is there a future for endothelin receptor antagonists in diabetic kidney disease?Annals of translational medicine · 2019Article
- Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?Kidney international reports · 2019Review
- Review
- 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 nephropathy: Time to withhold development and progression - A review.Journal of advanced research · 2017Review
- New therapeutic agents in diabetic nephropathy.The Korean journal of internal medicine · 2017Review
- Using systems biology to evaluate targets and mechanism of action of drugs for diabetes comorbidities.Diabetologia · 2016Review
Corrections and comments
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Authors and funding
18 authors at 14 institutions in 9 countries.
Funding
Abstract
backgroundA recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes.
designWe used the PRE score on data from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes.
methodsWe performed a post-hoc analysis of the RADAR/JAPAN randomized clinical trials in which 211 patients with type-2 diabetes and nephropathy were randomly assigned to atrasentan 0.75 mg/day, 1.25 mg/day, or placebo. A PRE score was developed in a background set of completed clinical trials using multivariate Cox models. The score was applied to baseline and week-12 risk marker levels of RADAR/JAPAN participants, to predict atrasentan effects on clinical outcomes. Outcomes were defined as doubling serum creatinine or end-stage renal disease and hospitalization for heart failure.
resultsThe PRE score predicted renal risk changes of -23% and -30% for atrasentan 0.75 and 1.25 mg/day, respectively. PRE scores also predicted a small non-significant increase in heart failure risk for atrasentan 0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit.
conclusionsBased on the RADAR/JAPAN study, with short-term changes in risk markers, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit. The ongoing hard outcome trial (SONAR) in type 2 diabetic patients with >30% albuminuria reduction to atrasentan will allow us to assess the validity of these predictions.
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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.