1 Year Trial Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy

Study Overview
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Brief Summary
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The general aim of this study is to compare telmisartan 80 mg with valsartan 160 mg in hypertensive patients with type 2 diabetes and overt nephropathy with adjusted blood pressure beyond the target of 130/80 mmHg after one year of treatment. The primary objective of this study is to show that telmisartan 80 mg is at least as effective (i.e., not inferior) and possibly superior to valsartan 160 mg in reducing 24 hour proteinuria after one year of treatment.

Detailed Description
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This is a randomised, double-blind, double-dummy, forced titration, multicentre, parallel group trial in patients with essential hypertension, diabetes mellitus type 2 and diabetic nephropathy. After a 4-6 week Run-in period, patients are randomised to one of the treatment groups and receive either Telmisartan 40 - 80 mg or Valsartan 80 - 160 mg. The treatment regimen is a forced titration with the lower dose given for 2 weeks and the higher dose given for the rest of the treatment period summing up to 52 weeks of treatment. During the treatment period, 8 visits to the investigator are scheduled in order to control blood pressure, renal function parameters and safety. In addition, parameters of endothelial function and oxidative stress are measured at baseline, 6 months and after one year of treatment. Study Hypothesis: Non-inferiority of telmisartan 80 mg compared to valsartan 160 mg will be tested using the following set of hypotheses: Null Hypothesis: The overall mean change from baseline in UPER (24 hour urinary protein excretion rate) for telmisartan 80 mg is inferior to that for valsartan 160 mg by 0.5 g/day or more. Alternative Hypothesis: The overall mean change from baseline in UPER (24 hour urinary protein excretion rate) for telmisartan 80 mg is less than 0.5 g/day worse than that for valsartan 160 mg. Comparison(s): In order to test the non-inferiority hypothesis, analysis of covariance with treatment and centre as main effects and baseline as a covariate will be performed. Time-to-event data will be analysed using the log-rank test.

Official Title
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A Prospective, Randomised, Double-blind, Double-dummy, Forced-titration, Multicentre, Parallel Group, One Year Treatment Trial to Investigate the Efficacy of Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy VIVALDI-Study

Conditions
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Diabetic Nephropathies, Hypertension

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus Aged 30-70 years of age Hypertension at screening defined as: an average cuff systolic blood pressure > 130 mmHg and/or diastolic blood pressure >80 mmHg in untreated patients OR patients receiving antihypertensive therapy (i.e., medications specifically prescribed to treat hypertension) Overt nephropathy defined by 24 hour proteinuria >= 900 mg and by serum creatinine below 265 mol/l (3.0 mg/dl) Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Telmisartan|nan|
|Drug: Valsartan|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline (Visit 6) in 24 hour proteinuria, after one year of treatment (study end) with telmisartan 80 mg versus valsartan 160 mg. |  | Baseline, after 1 year of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 24-hour urinary albumin excretion rate (UAER). |  | Baseline, after 1 year of treatment | 
| Change from baseline in 24-hour urinary sodium excretion rate. |  | Baseline, after 1 year of treatment | 
| Change from baseline in serum creatinine. |  | Baseline, after 1 year of treatment | 
| Change from baseline in creatinine clearance |  | Baseline, after 1 year of treatment | 
| Change from baseline in estimated glomerular filtration rate (eGFR). |  | Baseline, after 1 year of treatment | 
| Change from baseline in plasma asymmetrical dimethylarginine (ADMA) levels. |  | Baseline, after 1 year of treatment | 
| Change from baseline in urine 8-iso-prostaglandin F2α levels |  | Baseline, after 1 year of treatment | 
| Change from baseline in serum high sensitive C-reactive protein (CRP) levels. |  | Baseline, after 1 year of treatment | 
| Time to a composite of a doubling of serum creatinine concentration , end-stage renal disease (ESRD), or all cause death |  | after 1 year of treatment | 
| Time to a composite of morbidity and mortality from cardiovascular causes (myocardial infarction (MI), stroke, first hospitalisation for heart failure or unstable angina, coronary or peripheral revascularisation). |  | after 1 year of treatment | 
| Change from baseline in insulin sensitivity (Homeostasis Model Assessment (HOMA) index). |  | Baseline, after 1 year of treatment | 
| Change from baseline in plasma adiponectin levels. |  | Baseline, after 1 year of treatment | 
| Change from baseline in BP endpoints (SBP, DBP and pulse pressure) |  | Baseline, after 1 year of treatment |