Optimal Dose of Irbesartan for Renoprotection in Type 2 Diabetic Patients With Persistent Microalbuminuria
Aim: To evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultra high doses of irbesartan in Type 2 diabetic patients with microalbuminuria Design: A double-masked randomized cross-over trial including 60 hypertensive Type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication. At inclusion, previous antihypertensive treatment will be discontinued and replaced with bendroflumethiazide 5 mg o.d. for the entire study. Following two months wash-out (baseline), patients will be treated randomly with irbesartan 300, 600 and 900 mg o.d., each dose for two months. End-points evaluated at the end of each study period include urinary albumin excretion rate (UAE, mean of three 24-hrs collections), 24-hrs blood pressure (ABP); and GFR (51Cr-EDTA).
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
|Official Title:||Optimal Dose of Irbesartan for Renoprotection in Type 2 Diabetic Patients With Persistent Microalbuminuria|
- urinary albumin excretion rate
- ambulatory blood pressure
- glomerular filtration rate
- serum potassium
- serum creatinine
- markers of endothelial function
- markers of inflammation
- genotypes with possible implications for the risk of cardiovascular disease
|Study Start Date:||September 2003|
|Estimated Study Completion Date:||November 2004|
The primary aim of our study is to evaluate the antiproteinuric effect of irbesartan 300, 600 and 900 mg once daily in type 2 diabetic patients with microalbuminuria. Secondary to evaluate the effect on 24-h ambulatory blood pressure, glomerular filtration rate (GFR), urinary TGF beta excretion, and markers of endothelial dysfunction, and finally to evaluate the association between treatment response and genotypes with possible implications for the risk of cardiovascular disease.
Patients 60 type 2 diabetic patients with persistent microalbuminuria (at least two out of three 24-h urinary collections with albumin excretion between 30 and 300 mg/24-h).
Duration of study 38 weeks (8 weeks wash-out and 30 weeks of double-blind randomized cross-over (treatment with irbesartan 300, 600 and 900 mg for 10 weeks at each dose level)).
Design The study consists of an eight week wash-out period followed by a double-blind randomized three 10 week treatment period cross-over trial (please see enclosed flow chart).
Wash-out period: Eight weeks prior to randomization all previous antihypertensive medication is discontinued and replaced by hydrochlorothiazide 25 mg once daily throughout the entire study period. Hydrochlorothiazide is added to reduce blood pressure elevation and edema formation during the trial and to eliminate the influence of varying dietary salt intake on the effects of irbesartan during the double blind treatment periods.
Double-blind cross-over periods: All patients receive treatment with irbesartan 300, 600 and 900 mg once daily in random order, without wash-out between treatment periods. All treatment periods are of 10 weeks duration. They consist of an initial two week titration period on irbesartan 300 mg o.d. to minimize the risk of adverse events including hypotension during cross-over in doses followed by an eight week period on the full dose for the given treatment level.
For safety reasons blood pressure, serum potassium and serum creatinine will be measured 4 weeks after the beginning of each treatment period (two weeks after the full dose of the treatment period is reached).
End-points are evaluated after the wash-out period (baseline) and at the end of each treatment period.
Methods Albuminuria is assessed by turbidimetry in three 24-h urinary samples. 24-h ambulatory blood pressure by the Takeda TM-2420/2421 device. GFR by plasma clearance of 51Cr-EDTA. DNA will be extracted from a venous sample to determine genotypes with possible implications for the risk of cardiovascular disease. Initially we will evaluate the influence of the ACE/ID- , Angiotensin II type I receptor (A1166C) - and the angiotensinogen (M235T) polymorphisms.
Endpoints Primary endpoint: change in albuminuria Secondary endpoints: 24-h ambulatory blood pressure, glomerular filtration rate (GFR), and to evaluate the association between treatment response genotypes with possible implications for the risk of cardiovascular disease
Please refer to this study by its ClinicalTrials.gov identifier: NCT00320879
|Steno Diabetes Center|
|Gentofte, Copenhagen, Denmark, 2820|
|Study Director:||Hans-Henrik Parving||Steno Diabetes Center, Gentofte, Denmark|
|Principal Investigator:||Kasper Rossing||Steno Diabetes Center, Gentofte, Denmark|