Preventing ESRD in Overt Nephropathy of Type 2 Diabetes
VALID
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
2 other identifiers
interventional
102
2 countries
15
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3 diabetes
Started May 2007
Longer than P75 for phase_3 diabetes
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2007
CompletedFirst Submitted
Initial submission to the registry
June 29, 2007
CompletedFirst Posted
Study publicly available on registry
July 2, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedJune 1, 2016
May 1, 2016
8.9 years
June 29, 2007
May 31, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Progression to ESRD (i.e. need for renal replacement therapy by chronic dialysis or renal transplantation)
4 times a year
Secondary Outcomes (1)
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.
4 times a year
Study Arms (3)
Benazepril
EXPERIMENTALvalsartan
EXPERIMENTALbenazepril/valsartan
EXPERIMENTALInterventions
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).
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).
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).
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Hospital "Azienda Ospedaliera Ospedali Riuniti di Bergamo" - Unit of Diabetology
Bergamo, Bergamo, 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 "Vittorio Emanuele-Ferrarotto-Santo Bambino"
Catania, Catania, Italy
Hospital " Casa Sollievo della Sofferenza" - Unit of Nephrology
San Giovanni Rotondo, Foggia, Italy
University "Federico II"
Napoli, Napoli, Italy
Hospital "G:Mazzini"
Teramo, Teramo, Italy
IRCCS San Raffaele - Unit of General Medicine
Milan, 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 "Azienda Ospedaliera di Treviglio-Caravaggio"Unit of Diabetology and Metabolic Diseases
Treviglio, Italy
Clinical Department of Endocrinology, Diabetes and Metabolic Diseases University Medical Centre Ljubljana
Ljubljana, 1000, Slovenia
Related Publications (2)
Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.
PMID: 38682786DERIVEDCohen DL, Townsend RR. Is there added value to adding ARB to ACE inhibitors in the management of CKD? J Am Soc Nephrol. 2009 Aug;20(8):1666-8. doi: 10.1681/ASN.2008040381. Epub 2008 Sep 5.
PMID: 18776118DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Giuseppe Remuzzi, MD
Mario Negri Institute for Pharmacological Research
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 29, 2007
First Posted
July 2, 2007
Study Start
May 1, 2007
Primary Completion
April 1, 2016
Study Completion
April 1, 2016
Last Updated
June 1, 2016
Record last verified: 2016-05