Preventing Microalbuminuria in Type 2 Diabetes - Full Text View

Sponsor:	Mario Negri Institute for Pharmacological Research
Collaborator:	Agenzia Italiana del Farmaco
Information provided by (Responsible Party):	Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:	NCT00503152

Purpose

In people with type 2 diabetes, microalbuminuria is a strong, independent risk factor for diabetic nephropathy and cardiovascular morbidity and mortality. ACE inhibitor therapy decreased the risk of microalbuminuria in hypertensive subjects with type 2 diabetes and normoalbuminuria by about 40%. Available data suggest that angiotensin II receptor blockers (ARBs) might have a similar renoprotective effect and that this effect might be increased by combined ACE inhibitor therapy.

The study will evaluate the effects, at similar blood pressure control (systolic/diastolic <130/80 mmHg), for a period of three years, of dual renin-angiotensin-system (RAS) blockade by benazepril and valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan alone on microalbuminuria and cardiovascular events in high-risk patients with type 2 diabetes, creatinine <1.5 mg/dl, no evidence of microalbuminuria but at high risk of renal disease, with hypertension and a urinary albumin excretion between 7 and 19 microgram/min. The relationship between albuminuria and cardiovascular outcomes will also be evaluated.

The study is expected to show a more effective prevention of microalbuminuria and cardiovascular events with combined than with single drug ACE inhibitor or ARB therapy. As compared to ACE inhibitor, ARB therapy is expected to have a similar effect on microalbuminuria, but an inferior cardioprotective effect. Applied to clinical practice, the findings should help preventing renal and cardiovascular complications, and related treatment costs, of type 2 diabetes.

Condition	Intervention	Phase
Diabetes	Drug: Benazepril Drug: Valsartan Drug: Benazepril/Valsartan	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Prospective, Randomized, Probe Trial to Evaluate Whether, at Comparable Blood Pressure Control, Combined Therapy With the ACEI Benazepril and the ARB Valsartan, Reduces the Incidence of Microalbuminuria More Effectively Than BEN or VAL Alone in Hypertensive Patients With Type 2 Diabetes and High-normal Albuminuria

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2 Urine and Urination

Drug Information available for: Benazepril hydrochloride Benazepril Valsartan Lotrel

U.S. FDA Resources

Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:

Development of persistent microalbuminuria (i.e. urinary albumin excretion rate >20 µg/min in at least 2 of 3 consecutive overnight urine collections confirmed in two consecutive visits). Whenever a patient will be found to have 2 of 3 collections in the [ Time Frame: 2 times a year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Regression to low-normal albuminuria (i.e. urinary albumin excretion rate <10 µg/min in at least 2 of 3 consecutive overnight urine collections confirmed in two consecutive visits); Albuminuria (considered as a continuous variable); Serum creatinine (v [ Time Frame: 2 times a year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1020
Study Start Date:	May 2007
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: benazepril	Drug: Benazepril After one month wash-out from previous RAS (ARB or ACE) inhibitor therapy, patients satisfying the inclusion/exclusion criteria will be randomly given equivalent doses (half the standard doses recommended by the manufacturer for blood pressure control) of benazepril (10 mg/day) or valsartan (160 mg/day) or one fourth of the standard doses of both agents in combination (benazepril 5 mg/day and valsartan 80 mg/day). If well tolerated, treatment will be up-titrated to full dose of benazepril (20 mg/day) or valsartan (320 mg/day) or one half of the standard doses of both agents in combination (benazepril 10 mg/day and valsartan 160 mg/day).
Experimental: valsartan	Drug: Valsartan After one month wash-out from previous RAS (ARB or ACE) inhibitor therapy, patients satisfying the inclusion/exclusion criteria will be randomly given equivalent doses (half the standard doses recommended by the manufacturer for blood pressure control) of benazepril (10 mg/day) or valsartan (160 mg/day) or one fourth of the standard doses of both agents in combination (benazepril 5 mg/day and valsartan 80 mg/day). If well tolerated, treatment will be up-titrated to full dose of benazepril (20 mg/day) or valsartan (320 mg/day) or one half of the standard doses of both agents in combination (benazepril 10 mg/day and valsartan 160 mg/day).
Experimental: benazepril/valsartan	Drug: Benazepril/Valsartan After one month wash-out from previous RAS (ARB or ACE) inhibitor therapy, patients satisfying the inclusion/exclusion criteria will be randomly given equivalent doses (half the standard doses recommended by the manufacturer for blood pressure control) of benazepril (10 mg/day) or valsartan (160 mg/day) or one fourth of the standard doses of both agents in combination (benazepril 5 mg/day and valsartan 80 mg/day). If well tolerated, treatment will be up-titrated to full dose of benazepril (20 mg/day) or valsartan (320 mg/day) or one half of the standard doses of both agents in combination (benazepril 10 mg/day and valsartan 160 mg/day).

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Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females >40 years old;
High-risk subjects with type 2 diabetes (WHO criteria);
History of diabetes not exceeding 25 years;
High blood pressure (systolic and/or diastolic blood pressure >135/85 mmHg or concomitant treatment with blood pressure lowering medications);
Serum creatinine concentration <1.5 mg/dl;
Overnight urinary albumin excretion (in at least 2 of 3 consecutive overnight urine collections) >7 and <20 µg/min;
Legal capacity;
Written informed consent.

Exclusion Criteria:

Uncontrolled diabetes (glycated hemoglobin >11%);
Specific contraindications or history of hypersensitivity to the study drugs;
Serum potassium ≥ 5.5 mEq/L despite diuretic therapy, and optimized metabolic and acid/base control;
Bilateral renal artery stenosis;
Previous history of allergy or intolerance, or evidence of immunologically-mediated renal disease, systemic diseases, cancer;
Drug or alcohol abuse;
Any chronic clinical conditions that may affect completion of the trial or confound data interpretation;
Pregnancy or lactating;
Women of childbearing potential without following a scientifically accepted form of contraception;
Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequence of the trial;
Evidence of an uncooperative attitude;
Any evidence that patient will not be able to complete the trial follow-up.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00503152

Contacts

Contact: piero ruggenenti, MD

0039 035 45351

ruggenenti@marionegri.it

Locations

Italy
Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" - Diabetologic Ambulatory of Ponte San Pietro	Recruiting
Ponte San Pietro, Bergamo, Italy
Contact: Antonio Belviso, MD 0039 035 603449 belvisoa@tiscali.it
Principal Investigator: Antonio Belviso, MD
Clinical Research Center for Rare Diseases "Aldo e Cele Daccò"	Recruiting
Ranica, Bergamo, Italy
Contact: Stefano Rota, MD 0039 035 4535321 rota@marionegri.it
Principal Investigator: Piero Ruggenenti, MD
Sub-Investigator: Stefano Rota, MD
Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" Unit of Diabetology and Metabolic Diseases	Recruiting
Romano di Lombardia, Bergamo, Italy
Contact: Antonio Bossi, MD 0039 0363 4241 antonio_bossi@ospedale.treviglio.bg.it
Principal Investigator: Antonio Bossi, MD
Sub-Investigator: Ilian Iliev, MD
Hospital "Bolognini"	Recruiting
Seriate, Bergamo, Italy
Principal Investigator: Ruggero Mangili, MD
Hospital "Azienda Ospedaliera di Treviglio-Caravaggio"Unit of Diabetology and Metabolic Diseases	Recruiting
Treviglio, Bergamo, Italy
Contact: antonio bossi, MD 0039 0363 4241 antoniobossi@ospedale.treviglio.bg.it
Principal Investigator: Antonio Bossi, MD
Sub-Investigator: Aneliya Parvanova, MD
Hospital "Casa Sollievo della Sofferenza" - Division of Endocrinology	Recruiting
San Giovanni Rotondo, Foggia, Italy
Contact: Salvatore De Cosmo, MD
Principal Investigator: Salvatore De Cosmo, MD
Sub-Investigator: Anna Rauseo, MD
Hospital "Azienda Ospedaliera Ospedali Riuniti di Bergamo" - Unit of Diabetology	Recruiting
Bergamo, Italy
Contact: Roberto Trevisan, MD 0039 035 266968 rtrevisan@ospedaliriuniti.bergamo.it
Principal Investigator: Roberto Trevisan, MD
Sub-Investigator: Elena Mondo, MD
IRCCS San Raffaele - Unit of General Medicine	Recruiting
Milano, Italy
Contact: Paolo Manunta, MD 0039 02 26431 manunta.paolo@hsr.it
Sub-Investigator: Gianpaolo Zerbini, MD
Principal Investigator: Paolo Manunta, MD
Azienda USL 2	Recruiting
Olbia, Italy
Contact: Giancarlo Tonolo, MD giancarlo.tonolo@aslolbia.it
Principal Investigator: Giancarlo Tonolo, MD
Sub-Investigator: Simonetta Caria, MD
Sub-Investigator: Sara Cherchi, MD

Sponsors and Collaborators

Mario Negri Institute for Pharmacological Research

Agenzia Italiana del Farmaco

Investigators

Study Director:

Piero Ruggenenti, MD

Mario Negri Institute for Pharmacological Research

More Information

No publications provided

Responsible Party:	Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:	NCT00503152 History of Changes
Other Study ID Numbers:	VARIETY, 2006-005954-62
Study First Received:	July 17, 2007
Last Updated:	May 24, 2012
Health Authority:	Italy: Ministry of Health

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Benazepril
Valsartan
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors

Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on May 24, 2012