Preventing ESRD in Overt Nephropathy of Type 2 Diabetes (VALID)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Agenzia Italiana del Farmaco
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT00494715
First received: June 29, 2007
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

Nephropathy of type 2 diabetes is the leading cause of end stage renal disease (ESRD) world-wide and is associated with a dramatic excess cardiovascular morbidity and mortality. Two randomized trials found that angiotensin II receptor blockers (ARBs) reduce the incidence of ESRD by about 30%, but have no appreciable effects on cardiovascular mortality. Available data suggest that ACE inhibitors might be similarly renoprotective and even more cardioprotective, but large scale trials on ACE inhibitors, alone or combined with ARBs, in overt nephropathy of type 2 diabetes are missing.

This study will compare the effects, at comparable blood pressure control (systolic/diastolic <130/80 mmHg), of dual renin-angiotensin-system (RAS) blockade by half dose of benazepril and valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan alone at full dose, 20 mg and 160 mg respectively, on ESRD and cardiovascular events in high-risk patients with type 2 diabetes and overt nephropathy, defined as serum creatinine >1.8 mg/dl and < 3.2 mg/dl and spot morning urine albumin to creatinine ratio >1000mg/g for the patients without previous ACE inhibitor and ARB therapy and >500mg/g for the patients with previous ACE inhibitor or ARB therapy and no specific contraindications to the study drugs. The relationships between renal and cardiovascular outcomes will also be evaluated.

102 patients will be treated for at least 3 years. At comparable blood pressure control, the study is expected to show a more effective reduction in ESRD and cardiovascular events with combined than with single drug ACE inhibitor or ARB therapy. As compared to ARB, ACE inhibitor therapy is expected to have a similar effect on ESRD, but a superior cardioprotective effect. Applied to clinical practice, the findings should help reducing 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 ACEI BEN and ARB VAL Reduces Progression to ESRD More Effectively Than BEN or VAL Alone in High Risk Patients With Type 2 Diabetes and Overt Nephropathy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression to ESRD (i.e. need for renal replacement therapy by chronic dialysis or renal transplantation) [ Time Frame: 4 times a year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Doubling of serum creatinine (versus baseline), Rate of GFR decline, Incidence of fatal and non-fatal cardiovascular events (stroke, acute myocardial infarction, sudden death), Albumin to creatinine ratio and 24-hour urinary protein excretion. [ Time Frame: 4 times a year ] [ Designated as safety issue: Yes ]

Enrollment: 102
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
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
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
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).

  Show Detailed Description

  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);
  • Serum creatinine concentration of 1.8 mg/dl or more (but less than 3.5 mg/dl);
  • Urinary albumin to creatinine ratio >1000mg/g for the patients without previous ACE inhibitor and ARB therapy and >500mg/g for the patients with previous ACE inhibitor or ARB therapy (in spot morning urine)
  • Legal capacity;
  • Written informed consent.

Exclusion Criteria:

  • Specific contraindications or history of hypersensitivity to the study drugs or other;
  • Serum potassium ≥ 6 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;
  • Dual RAS blockade with an ACE inhibitor and an ARB.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00494715

Locations
Italy
Clinical Research Center for Rare Diseases "Aldo e Cele Daccò"
Ranica, Bergamo, Italy
Hospital "Bolognini"
Seriate, Bergamo, Italy
Hospital "S.Marta e S.Venera"
Acireale, Catania, Italy
Hospital " Casa Sollievo della Sofferenza" - Unit of Nephrology
San Giovanni Rotondo, Foggia, Italy
Hospital "Azienda Ospedaliera Ospedali Riuniti di Bergamo" - Unit of Diabetology
Bergamo, Italy
Hospital "Vittorio Emanuele-Ferrarotto-Santo Bambino"
Catania, Italy
IRCCS San Raffaele - Unit of General Medicine
Milan, Italy
University "Federico II"
Napoli, Italy
Hospital "Azienda Ospedaliera di Parma" - Unit of Nephrology
Parma, Italy
Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" - Ambulatory of Ponte San Pietro
Ponte San Pietro, Italy
Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" Unit of Diabetology and Metabolic Diseases
Romano di Lombardia, Italy
University - AUSL 1 - Institute of Medical Pathology
Sassari, Italy
Hospital "G:Mazzini"
Teramo, Italy
Hospital "Azienda Ospedaliera di Treviglio-Caravaggio"Unit of Diabetology and Metabolic Diseases
Treviglio, Italy
Slovenia
Clinical Department of Endocrinology, Diabetes and Metabolic Diseases University Medical Centre Ljubljana
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Agenzia Italiana del Farmaco
Investigators
Study Director: Giuseppe Remuzzi, MD Mario Negri Institute for Pharmacological Research
  More Information

No publications provided by Mario Negri Institute for Pharmacological Research

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT00494715     History of Changes
Other Study ID Numbers: VALID, 2006-005951-14
Study First Received: June 29, 2007
Last Updated: August 26, 2013
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic 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 July 24, 2014