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

Purpose

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).

Condition	Intervention	Phase
Type 2 Diabetes Nephropathy	Drug: MK0954, losartan / Duration of Treatment: mean 3.4 years Drug: Placebo / Duration of Treatment: mean 3.4 years	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Losartan Losartan potassium

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Combined endpoint of doubling of serum creatinine, ESRD or death.

Secondary Outcome Measures:

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

Estimated Enrollment:	1513
Study Start Date:	June 1996

Eligibility

Ages Eligible for Study:	31 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00308347

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

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.

Eijkelkamp WB, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF, Shahinfar S, Gleim GW, Weir MR, Brenner BM, de Zeeuw D. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial. J Am Soc Nephrol. 2007 May;18(5):1540-6. Epub 2007 Apr 4.

Eijkelkamp WB, Zhang Z, Brenner BM, Cooper ME, Devereux RB, Dahlöf B, Ibsen H, Keane WF, Lindholm LH, Olsen MH, Parving HH, Remuzzi G, Shahinfar S, Snapinn SM, Wachtell K, de Zeeuw D. Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies. J Hypertens. 2007 Apr;25(4):871-6.

Keane WF, Zhang Z, Lyle PA, Cooper ME, de Zeeuw D, Grunfeld JP, Lash JP, McGill JB, Mitch WE, Remuzzi G, Shahinfar S, Snapinn SM, Toto R, Brenner BM; RENAAL Study Investigators. Risk scores for predicting outcomes in patients with type 2 diabetes and nephropathy: the RENAAL study. Clin J Am Soc Nephrol. 2006 Jul;1(4):761-7. Epub 2006 May 17.

Mohanram A, Zhang Z, Shahinfar S, Lyle PA, Toto RD. The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes. Kidney Int. 2008 Mar;73(5):630-6. Epub 2007 Dec 19.

Parving HH, de Zeeuw D, Cooper ME, Remuzzi G, Liu N, Lunceford J, Shahinfar S, Wong PH, Lyle PA, Rossing P, Brenner BM. ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy. J Am Soc Nephrol. 2008 Apr;19(4):771-9. Epub 2008 Jan 16.

Tershakovec AM, Keane WF, Zhang Z, Lyle PA, Appel GB, McGill JB, Parving HH, Cooper ME, Shahinfar S, Brenner BM. Effect of LDL cholesterol and treatment with losartan on end-stage renal disease in the RENAAL study. Diabetes Care. 2008 Mar;31(3):445-7. Epub 2007 Dec 10.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miao Y, Ottenbros SA, Laverman GD, Brenner BM, Cooper ME, Parving HH, Grobbee DE, Shahinfar S, de Zeeuw D, Lambers Heerspink HJ. Effect of a reduction in uric acid on renal outcomes during losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial. Hypertension. 2011 Jul;58(1):2-7. Epub 2011 May 31.

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck & Co., Inc.
ClinicalTrials.gov Identifier:	NCT00308347 History of Changes
Other Study ID Numbers:	2006_020, MK0954-147
Study First Received:	March 27, 2006
Last Updated:	May 12, 2009
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Losartan

Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013