Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial

on behalf of the VALID Study Organization

Research output: Contribution to journalArticle

Abstract

Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.

Original languageEnglish
Pages (from-to)1177-1190
Number of pages14
JournalDiabetes, Obesity and Metabolism
Volume21
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Valsartan
Type 2 Diabetes Mellitus
Randomized Controlled Trials
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Confidence Intervals
Chronic Kidney Failure
Creatinine
Blood Pressure
Slovenia
Therapeutics
Intention to Treat Analysis
Serum
Proteinuria
Italy
benazepril

Keywords

  • diabetic nephropathy
  • phase III study
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes : A prospective, randomized, controlled trial. / on behalf of the VALID Study Organization.

In: Diabetes, Obesity and Metabolism, Vol. 21, No. 5, 01.05.2019, p. 1177-1190.

Research output: Contribution to journalArticle

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title = "Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial",
abstract = "Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3{\%}) and nine on combination therapy (27.3{\%}) progressed to ESRD, versus five on valsartan (13.9{\%}). Differences between benazepril (hazard ratio [HR] 3.59, 95{\%} confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95{\%} CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95{\%} CI 1.50–17.75, P = 0.009 and HR 4.75, 95{\%} CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.",
keywords = "diabetic nephropathy, phase III study, type 2 diabetes",
author = "{on behalf of the VALID Study Organization} and Piero Ruggenenti and Matias Trillini and {P. Barlovic}, Drazenka and Monica Cortinovis and Antonio Pisani and Aneliya Parvanova and Iliev, {Ilian P.} and Barbara Ruggiero and Stefano Rota and Aparicio, {Maria C.} and Annalisa Perna and Francesco Peraro and Olimpia Diadei and Flavio Gaspari and Fabiola Carrara and Nadia Stucchi and Davide Martinetti and Andrej Janez and Nadan Gregoric and Eleonora Riccio and Bossi, {Antonio C.} and Roberto Trevisan and Paolo Manunta and Giovanni Battaglia and Salvatore David and Filippo Aucella and Antonio Belviso and Andrea Satta and Giuseppe Remuzzi",
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T1 - Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes

T2 - A prospective, randomized, controlled trial

AU - on behalf of the VALID Study Organization

AU - Ruggenenti, Piero

AU - Trillini, Matias

AU - P. Barlovic, Drazenka

AU - Cortinovis, Monica

AU - Pisani, Antonio

AU - Parvanova, Aneliya

AU - Iliev, Ilian P.

AU - Ruggiero, Barbara

AU - Rota, Stefano

AU - Aparicio, Maria C.

AU - Perna, Annalisa

AU - Peraro, Francesco

AU - Diadei, Olimpia

AU - Gaspari, Flavio

AU - Carrara, Fabiola

AU - Stucchi, Nadia

AU - Martinetti, Davide

AU - Janez, Andrej

AU - Gregoric, Nadan

AU - Riccio, Eleonora

AU - Bossi, Antonio C.

AU - Trevisan, Roberto

AU - Manunta, Paolo

AU - Battaglia, Giovanni

AU - David, Salvatore

AU - Aucella, Filippo

AU - Belviso, Antonio

AU - Satta, Andrea

AU - Remuzzi, Giuseppe

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.

AB - Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.

KW - diabetic nephropathy

KW - phase III study

KW - type 2 diabetes

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DO - 10.1111/dom.13639

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