Bichu et al Trial/year HOPE19 2001 IDNT20 2001 Table 1 Recent clinical trials leading up to the AMADEO study Patient population High-risk patients without known diabetes N 5720 Treatment arms Ramipril/placebo Hypertension with diabetic nephropathy 1715 Irbesartan/amlodipine/ placebo IRMA222 2001 Type 2 diabetes with MA 590 Irbesartan/placebo RENAAL23,24 2001 Type 2 diabetes with nephropathy 1513 Losartan/placebo MARVAL25 2002 Type 2 diabetes with MA 332 Valsartan/amlodipine Type 2 diabetes and HTN but with normo- albuminuria Type 2 diabetes with early nephropathy Type 2 diabetes, HTN, GFR 80 mL/min, and normo- or micro- albuminuria. Type 2 diabetes and UACR 100-300mg/g, Cr 1.5 mg/dl (men) and 1.3 mg/dl (women). HTN SBP/ DBP 130/80 mmHg patients with type 2 diabetes, proteinuria ( 900 mg/24 h) and Cr ( 3.0 mg/dL) TRENDY30 2007 96 Telmisartan/ramipril INNOVATION32 2007 527 Telmisartan (80/40 mg)/placebo VIVALDI31 2008 885 Telmisartan/valsartan BENEDICT26,27 2004 1204 Trandalopril/ verapamil/placebo Development of persistent MA DETAIL29 2004 250 Telmisartan/enalapril 132 Vascular Health and Risk Management 2009:5 Primary endpoint New onset overt nephropathy Composite of development of ESRD, doubling Cr. Time to onset of diabetic nephropathy Composite of doubling of Cr, development of ESRD. % change in UAER from BL to 24 Wks. Change in the GFR (determined by measuring the plasma clearance of iohexol) Increase in renal plasma ﬂow (RPF) Transition rate incipient to overt Nephropathy, UACR 300 mg/g, and increase 30% from baseline at 2 consecutive 4-week visits. Change from BL of 24 h proteinuria. Final outcome 22% Reduction in new onset overt nephropathy (RR 0.66; 95% CI 0.51–0.85; p 0.001). Irbesartan signiﬁcantly reduced primary composite end point by 20% compared to placebo (p 0.02) and by 23% compared to amlodipine (p 0.006). Irbesartan reduced risk of primary end point (HR 0.30; 95% CI 0.14–0.61; p 0.001 for 300 mg irbesartan; HR 0.61; 95% CI 0.34–0.99; p 0.08 for 150 mg irbesartan. Losartan signiﬁcantly reduced the composite end point by 16% (p 0.02), but not death. UAER at 24 wk was reduced by 44% with valsartan and 8% with amlodipine (p 0.001); valsartan signiﬁcantly reversed MA to normal albuminuria For developing end point AF = 0.39 for trandalopril + verapamil vs placebo.AF = 0.44 for trandalopril vs placebo and AF = 0.83 with verapamil vs placebo. Change in the GFR was −17.9 mL/min/1.73 m2 of body- surface area with telmisartan, as compared with −14.9 mL/min/1.73 m2 with enalapril, for a treatment dif- ference of −3.0 mL/min/1.73 m2 (95 % CI −7.6–1.6 mL/ min/1.73 m2). Telmisartan increased RPF from 652.0 ± 27.0 to 696.1 ± 31.0 mL/min (p = 0.047), whereas ramipril produced no signiﬁcant changes in RPF. (r = 0.47, p 0.001). Transition rates to overt nephropathy were 16.7% with 80 mg telmisartan (n = 168), 22.6% with 40 mg telmisartan (n = 172), and 49.9% with placebo (n = 174) (both telmisartan doses/ placebo, p 0.0001). Comparable reduction in 24 h urinary protein excretion rates. Geometric mean reduction (95% conﬁdence interval) telmisartan, 33% (27%–39%); valsartan, 33% (27%–38%). (Continued)