ASCEND - A Randomised, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Effect of the Endothelin Receptor Antagonist Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death in Patients With Type 2 Diabetes Mellitus and Diabetic Nephropathy

The purpose of this study is to determine whether avosentan (SPP301) is effective in decreasing morbidity and mortality in patients with diabetic nephropathy.

开始日期2005-07-01

申办/合作机构

Speedel Pharma AG

100 项与阿伏生坦相关的临床结果

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100 项与阿伏生坦相关的转化医学

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100 项与阿伏生坦相关的专利（医药）

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项与阿伏生坦相关的文献（医药）

2021-11-07·Cureus

Endothelin Receptor Antagonists as a Potential Treatment of Diabetic Nephropathy: A Systematic Review

Review

作者: Veerapalli, Harish ; Castaneda, Everardo E ; Lankala, Chetan Reddy ; Aziz, Afia ; Rockferry, Amy G ; Ahmad, Noorain ; Hamid, Pousette

Diabetic nephropathy is becoming a more predominant cause of end-stage renal disease, as the prevalence of diabetes mellitus worldwide is on the rise. In this systematic review, we aimed to define the role of endothelin receptor antagonists, in the prevention and treatment of diabetic nephropathy, in addition to determining their safety. For this review, PubMed, Google Scholar, and Cochrane Library databases, in addition to ClinicalTrials.gov, were searched for publications in the last 20 years. We included 14 studies, seven randomized control trials, and seven post hoc analyses in this paper. Atrasentan decreased albuminuria, reduced blood pressure, and improved lipid profiles with more manageable fluid overload-related adverse events than avosentan and bosentan. Overall, endothelin receptor antagonists, in combination with renin-angiotensin-aldosterone system inhibitors, effectively reduce albuminuria and prevent the progression of diabetic kidney disease. However, more extensive clinical trials still need to be conducted to confirm these relationships and to learn more about the specific factors affecting their efficacy in individual patients.

2021-01-01·Diabetic Medicine2区 · 医学

Efficacy and safety of endothelin receptor antagonists in type 2 diabetic kidney disease: A systematic review and meta‐analysis of randomized controlled trials

2区 · 医学

Review

作者: Chi, J. ; Zhou, Y. ; Huang, Y. ; Lv, W. ; Wang, Y. G. ; Dong, B.

AbstractAimTo analyse the efficacy and safety of endothelin receptor antagonists for people with diabetic kidney disease.MethodsRandomized controlled trials comparing endothelin receptor antagonists with placebo in people with diabetic kidney disease were identified through PubMed, Embase and the Cochrane Library. We used a random‐effect model to calculate the mean difference or risk ratio with the 95% CI.ResultsSeven studies with a total of 4730 participants were included. Overall, endothelin receptor antagonists significantly reduced albuminuria compared with placebo (standardized mean difference –0.48, 95% CI –0.64 to –0.33). Atrasentan, in particular, effectively reduced albuminuria (standardized mean difference –0.58, 95% CI –1.00 to –0.17) and the risk of composite renal endpoints (risk ratio 0.65; 95% CI 0.49 to 0.88), with insignificant change in the rate of congestive heart failure (risk ratio 1.40, 95% CI 0.76 to 2.56) and mortality (risk ratio 1.11, 95% CI 0.77 to 1.61). In contrast, although avosentan reduced albuminuria (standardized mean difference –0.47, 95% CI –0.57 to –0.36) and the risk of composite renal endpoints (risk ratio 0.63, 95% CI 0.42 to 0.94), it was associated with a significant increase in congestive heart failure risk (risk ratio 2.61, 95% CI 1.36 to 5.00) and an insignificant increase in mortality risk (risk ratio 1.50, 95% CI 0.81, 2.78). No significant change in efficacy or safety outcomes with bosentan was detected. Dose–response analysis indicated that 0.75 mg/day atrasentan is expected to be optimal for renoprotection, with maximal albuminuria reduction and minimal fluid retention events.ConclusionsAmong the endothelin receptor antagonists, atrasentan and avosentan, but not bosentan, are effective for renoprotection in people with diabetic kidney disease. Compared with other types and doses, atrasentan 0.75 mg/day is the most promising, with maximal albuminuria reduction and minimal fluid retention. Vigilant monitoring of congestive heart failure risk is needed in future clinical practice. (PROSPERO registration no. CRD42020169840).

2017-06-03·Expert Opinion on Investigational Drugs2区 · 医学

Atrasentan for the treatment of diabetic nephropathy

2区 · 医学

Review

作者: Ruiz-Ortega, Marta ; Egido, Jesus ; Mas, Sebastian ; Sanz, Ana Belen ; Rojas-Rivera, Jorge ; Gonzalez Parra, Emilio ; Gomez-Guerrero, Carmen

INTRODUCTIONEndothelin-1 (ET-1) is the most potent vasoconstrictor, and is involved in the renal regulation of salt and water homeostasis. When produced in excess in the kidney, ET-1 promotes proteinuria and tubulointerstitial injury. There is great interest in the clinical use of endothelin receptor antagonists (ERAs) in chronic kidney disease (CKD), mainly in diabetic nephropathy (DN). Areas covered: Physiopathological actions of ET-1 on the kidney. Both dual ETAR/ET_BR (bosentan) or ET_AR specific endothelin antagonists (avosentan and atrasentan, among others), which have progressed to early clinical development, with particular emphasis on atrasentan. Expert opinion: Different phase I and II clinical trials with ERAs in DN, mostly with atrasentan, have shown that these drugs have a marked anti-proteinuric effect on residual proteinuria when administered as add-on therapy in addition to ACEi or ARAII treatment. In the past few years, a series of randomized controlled trials investigating new approaches to DN have provided negative or inconclusive data, or even were terminated due to safety concerns or lack of efficacy. Therefore, we eagerly but cautiously await the results of the ongoing SONAR trial with atrasentan in more than 4,000 patients including assessment of renal and cardiovascular hard-end points (estimated primary completion date, July 2018).

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05290

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床1期	美国	Speedel Pharma AG	2005-07-01
糖尿病肾病	临床1期	美国	Speedel Pharma AG	2005-07-01
糖尿病肾病	临床1期	美国	Spera Pharma, Inc.初创企业	2005-07-01
终末期肾脏病	临床1期	美国	Speedel Pharma AG	2005-07-01
青光眼	临床前	瑞士	Speedel Experimenta Ltd	2009-04-01
青光眼	临床前	美国	Icahn School of Medicine at Mount Sinai	2009-04-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00120328 (ASCEND, EASD2013)	临床3期	心脏衰竭 body weight \| haemoglobin \| cholesterol levels ... 更多	1,392	Avosentan	齋網鹽艱膚鏇憲憲膚齋(蓋齋蓋憲廠淵鹽鬱齋蓋) = 窪鹽膚遞壓窪範襯淵簾淵憲窪顧襯齋蓋夢範鏇 (蓋廠糧積選衊範鹹簾範, 0.0 ~ 2.0) 更多	不佳	2013-09-25
				Placebo	-
ASCEND (ASN2012)	N/A	心脏衰竭	761	Avosentan 25mg	窪觸餘築鹹繭齋壓願簾(獵築鹹鏇鑰遞衊糧築衊) = an excess of congestive heart failure (CHF) events occurred in the avosentan treatment arms which was likely due to increased sodium/fluid retention and led to premature termination of the trial 膚襯選網鏇齋築膚餘願 (選膚範鑰積觸選憲夢鑰 )	不佳	2012-10-30
				Avosentan 50mg