Preventing ESRD in Overt Nephropathy of Type 2 Diabetes (VALID)
This study is currently recruiting participants.
Verified February 2013 by Mario Negri Institute for Pharmacological Research
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:
NCT00494715
First received: June 29, 2007
Last updated: February 22, 2013
Last verified: February 2013
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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 ]
| Estimated 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00494715
Contacts
| Contact: giuseppe remuzzi, MD | 0039 035 319888 | gremuzzi@marionegri.it |
Locations
| Italy | |
| Clinical Research Center for Rare Diseases "Aldo e Cele Daccò" | Recruiting |
| Ranica, Bergamo, Italy | |
| Contact: Stefano Rota, MD 0039 035 4535321 | |
| Sub-Investigator: Stefano Rota, MD | |
| Hospital "Bolognini" | Recruiting |
| Seriate, Bergamo, Italy | |
| Principal Investigator: Ruggero Mangili, MD | |
| Hospital "S.Marta e S.Venera" | Recruiting |
| Acireale, Catania, Italy | |
| Contact: Maurizio Garozzo, MD mauriziocom@hotmail.com | |
| Principal Investigator: Giovanni Battaglia, MD | |
| Sub-Investigator: Maurizio Garozzo, MD | |
| Hospital " Casa Sollievo della Sofferenza" - Unit of Nephrology | Recruiting |
| San Giovanni Rotondo, Foggia, Italy | |
| Contact: Filippo Aucella, MD 0039 0882 410367 | |
| Sub-Investigator: Rachele Grifa, MD | |
| Principal Investigator: Filippo Aucella, 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 | |
| Hospital "Vittorio Emanuele-Ferrarotto-Santo Bambino" | Not yet recruiting |
| Catania, Italy | |
| Contact: Antonio Granata, MD antonio.granata4@tin.it | |
| Principal Investigator: Antonio Granata, MD | |
| IRCCS San Raffaele - Unit of General Medicine | Recruiting |
| Milan, Italy | |
| Contact: Paolo Manunta, MD 0039 02 26431 manunta.paolo@hsr.it | |
| Sub-Investigator: Marialuisa Querques, MD | |
| Principal Investigator: Paolo Manunta, MD | |
| University "Federico II" | Recruiting |
| Napoli, Italy | |
| Contact: Antonio Pisani, MD antonio.pisani@libero.it | |
| Principal Investigator: Antonio Pisani, MD | |
| Sub-Investigator: Gennaro Argentino, MD | |
| Hospital "Azienda Ospedaliera di Parma" - Unit of Nephrology | Recruiting |
| Parma, Italy | |
| Contact: Salvatore David, MD 0039 0521 293561 davidren@unipr.it | |
| Principal Investigator: Salvatore David, MD | |
| Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" - Ambulatory of Ponte San Pietro | Recruiting |
| Ponte San Pietro, Italy | |
| Contact: Antonio Belviso, MD 0039 035 603449 belvisoa@tiscali.it | |
| Principal Investigator: Antonio Belviso, MD | |
| Hospital "Azienda Ospedaliera di Treviglio e Caravaggio" Unit of Diabetology and Metabolic Diseases | Not yet recruiting |
| Romano di Lombardia, Italy | |
| Contact: Antonio Bossi, MD 0039 0363 4241 antonio_bossi@ospedale.treviglio.bg.it | |
| Principal Investigator: Antonio Bossi, MD | |
| Sub-Investigator: Ilian Iliev, MD | |
| University - AUSL 1 - Institute of Medical Pathology | Recruiting |
| Sassari, Italy | |
| Contact: Andrea Satta, MD 0039 079 228442 amesatta@uniss.it | |
| Principal Investigator: Andrea Satta, MD | |
| Sub-Investigator: Giovanna Farre, MD | |
| Hospital "G:Mazzini" | Recruiting |
| Teramo, Italy | |
| Contact: Goffredo Del Rosso, MD goffredo.delrosso@aslteramo.it | |
| Principal Investigator: Goffredo Del Rosso, MD | |
| Sub-Investigator: Patrizia Santarelli, MD | |
| Hospital "Azienda Ospedaliera di Treviglio-Caravaggio"Unit of Diabetology and Metabolic Diseases | Recruiting |
| Treviglio, Italy | |
| Contact: Antonio Bossi, MD 0039 0363 4241 antonio_bossi@ospedale.treviglio.bg.it | |
| Principal Investigator: Antonio Bossi, MD | |
| Sub-Investigator: Aneliya Parvanova, MD | |
| Slovenia | |
| Clinical Department of Endocrinology, Diabetes and Metabolic Diseases University Medical Centre Ljubljana | Recruiting |
| Ljubljana, Slovenia, 1000 | |
| Contact: Andrej Janez, MD andrej.janez@kclj.si | |
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: | February 22, 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 June 17, 2013