A Research Study to Evaluate the Renal (Kidney) Protective Effects of Losartan in Patients With Non-insulin Dependent Diabetes (0954-147)(COMPLETED)

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00308347
• Other study ID #: 0954-147
• Secondary ID: 2006_020
• Status: Completed
• Phase: Phase 3
• Start date: May 1996
• Est. completion date: April 2001

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1513
• Est. completion date: April 2001
• Est. primary completion date: February 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: 31 Years to 70 Years

Eligibility

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 Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Kidney Diseases
• Nephropathy
• Type 2 Diabetes

Intervention

Drug:
• MK0954, losartan / Duration of Treatment: mean 3.4 years

• Placebo / Duration of Treatment: mean 3.4 years

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & Publications (19)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. doi: 10.1681/ASN.2007050582. Epub 2008 Jan 16. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined endpoint of doubling of serum creatinine, ESRD or death.
Secondary	Secondary parameters: number of cardiovascular events and changes in proteinuria. Tertiary parameters: quality of life and healthcare resource utilization.