A Research Study to Evaluate the Renal (Kidney) Protective Effects of Losartan in Patients With Non-Insulin Dependent Diabetes

Condition(s) targeted: Type 2 Diabetes and Nephropathy

Intervention: MK0954, losartan / Duration of Treatment: mean 3.4 years (Drug); Placebo / Duration of Treatment: mean 3.4 years (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Merck

Official(s) and/or principal investigator(s):
Medical Monitor, Study Director, Affiliation: Merck

Evaluate the effect of Losartan in reducing kidney disease in patients with Non-insulin Dependent Diabetes and Nephropathy (kidney damage that usually accompanies late stage Diabetes Mellitus).

Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Renal Protective Effects of Losartan in Patients With Non-Insulin Dependent Diabetes Mellitus and Nephropathy

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Combined endpoint of doubling of serum creatinine, ESRD or death.

Secondary outcome: Secondary parameters: number of cardiovascular events and changes in proteinuria. Tertiary parameters: quality of life and healthcare resource utilization.

Minimum age: 31 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diabetes diagnosed after the age of 30

- Insulin not required within 6 months of first being diagnosed with Non-insulin

Dependent Diabetes Mellitus

- No history of diabetic ketoacidosis

- Patients may be currently treated with diet, oral hypoglycemics or insulin

- Patients must have proteinuria defined as: Urine protein >1+ on dipstick at the

initial screening visit

- Patients with hypertension (high blood pressure) must have a sitting blood pressure

>200/110 mm Hg at Visit 1

Exclusion Criteria:

- Patients with insulin-dependent diabetes mellitus (juvenile onset)

- Patients treated with an ACE inhibitor or angiotensin II antagonist (AIIA) for >5

years

- Patients treated with ACE inhibitor or AIIA therapy for 5 years or less may enter the

study provided therapy is discontinued during the 6 week screening period prior to randomization

- History of myocardial infarction (MI) (heart attack) or coronary artery bypass graft

(CABG) surgery within the past 1 month

- History of cerebral vascular accident (CVA) (stroke) or percutaneous transluminal

coronary angioplasty (PTCA) within the past 6 months

- History of transient ischemic attacks (TIA) within the past year. Patients with

unstable angina are excluded until stabilized

- Heart failure requiring ACE inhibitor therapy

- Steroids (oral or parenteral) or immunosuppressives are not permitted. Debilitating

psychological illness

- Evidence of significant hepatic (liver) dysfunction: History of allergy to losartan

- Known positive test for HIV or patients known to be hepatitis B or C antigen carriers

- Pregnant or nursing women

- Females of childbearing age must either be surgically sterilized or, if sexually

active, using an effective form of contraception and may enter only if an exclusionary pregnancy test is done within approximately 72 hours prior to randomization

- Pregnancy tests will be done every 3 months during the study and at the time of

discontinuation

Related publications:

Arredondo A, Burke TA, Carides GW, Lemus E, Querol J. The impact of losartan on the lifetime incidence of ESRD and costs in Mexico. Rev Invest Clin. 2005 May-Jun;57(3):399-405.

Carides GW, Shahinfar S, Dasbach EJ, Keane WF, Gerth WC, Alexander CM, Herman WH, Brenner BM; RENAAL Investigators. The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy. Pharmacoeconomics. 2006;24(6):549-58.

Appel GB, Radhakrishnan J, Avram MM, DeFronzo RA, Escobar-Jimenez F, Campos MM, Burgess E, Hille DA, Dickson TZ, Shahinfar S, Brenner BM; RENAAL Study. Analysis of metabolic parameters as predictors of risk in the RENAAL study. Diabetes Care. 2003 May;26(5):1402-7.

Bakris GL, Weir MR, Shanifar S, Zhang Z, Douglas J, van Dijk DJ, Brenner BM; RENAAL Study Group. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch Intern Med. 2003 Jul 14;163(13):1555-65.

Remuzzi G, Ruggenenti P, Perna A, Dimitrov BD, de Zeeuw D, Hille DA, Shahinfar S, Carides GW, Brenner BM; RENAAL Study Group. Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results. J Am Soc Nephrol. 2004 Dec;15(12):3117-25.

de Zeeuw D, Ramjit D, Zhang Z, Ribeiro AB, Kurokawa K, Lash JP, Chan J, Remuzzi G, Brenner BM, Shahinfar S. Renal risk and renoprotection among ethnic groups with type 2 diabetic nephropathy: a post hoc analysis of RENAAL. Kidney Int. 2006 May;69(9):1675-82.

Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9.

de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004 Jun;65(6):2309-20.

Mohanram A, Zhang Z, Shahinfar S, Keane WF, Brenner BM, Toto RD. Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. Kidney Int. 2004 Sep;66(3):1131-8.

de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation. 2004 Aug 24;110(8):921-7. Epub 2004 Aug 9.

Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, Ribeiro AB, Shahinfar S, Simpson RL, Snapinn SM, Toto R; RENAAL Study Investigators. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int. 2003 Apr;63(4):1499-507.

Jafar TH, Schmid CH, Stark PC, Toto R, Remuzzi G, Ruggenenti P, Marcantoni C, Becker G, Shahinfar S, De Jong PE, De Zeeuw D, Kamper AL, Strangaard S, Levey AS. The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis. Nephrol Dial Transplant. 2003 Oct;18(10):2047-53.

Herman WH, Shahinfar S, Carides GW, Dasbach EJ, Gerth WC, Alexander CM, Cook JR, Keane WF, Brenner BM. Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation. Diabetes Care. 2003 Mar;26(3):683-7.

Starting date: June 1996
Last updated: January 15, 2007