VA Cooperative Studies Program (CSP)

Investigator Access

What's Available

Check with the study contact and publications for information on a public dataset, data archive, data enclave, or website where data might be available.

Available Documentation

Dates Data are Available

Access Criteria

Study Characteristics

Objectives

To evaluate the combination of losartan, an angiotensin converting enzyme inhibitor (ACEI), with lisinopril, an angiotensin receptor blocker (ARB), as compared with standard treatment with losartan alone on the progression of kidney disease in individuals with Type 2 diabetes and overt nephropathy.

Era of Service

All

Population

Veterans with Type 2 diabetes with overt nephropathy (albumin-to-creatinine ratio of at least 300) and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m2 of body-surface area (99.2% male)

Study Design

Double-blind, randomized, controlled clinical trial

Time Period

July 2008 – October 2014

Note: The intervention was stopped on November 7, 2012 for safety concerns after an interim analysis

Setting

32 VA medical centers

N

1,448 participants

Response Rate

A total of 4,346 patients were screened, 1,648 were enrolled, and 1,448 underwent randomization (724 in each group).

Recruitment Method

Participating VA medical centers recruited patients meeting the eligibility criteria. Those providing written informed consent were enrolled in the study.

Compensation

None

Data Collected

• Demographic characteristics
• Baseline health indices (body mass index, coronary artery disease, retinopathy, congestive heart failure, blood pressure, cholesterol, triglycerides, glycated hemoglobin, serum creatinine, serum potassium, urinary albumin-to-creatinine ratio, and use of medications)
• Kidney function monitored by estimated GFR
• End-stage renal disease
• Albuminuria
• Cardiovascular events, including myocardial infarction, stroke, hospitalization for congestive heart failure
• Safety outcomes, including all-cause mortality, serious adverse events, hyperkalemia, and acute kidney injury
• Serious adverse events (e.g., hospitalizations)

Data Collection Methods

• Patient medical records
• Self-report questionnaires
• Overnight fast blood draws and ethylenediaminetetraacetic acid (EDTA) plasma was aliquoted, frozen, and shipped to a central repository

Funding Source

VA Cooperative Studies Program

Contact

Jane Zhang, PhD; Jane.Zhang@va.gov

Selected Publications

Fried LF, Duckworth W, Zhang JH, O'Connor T, Brophy M, Emanuele N, Huang GD, McCullough PA, Palevsky PM, Seliger S, Warren SR, Peduzzi P; VA NEPHRON-D Investigators. Design of combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). Clin J Am Soc Nephrol. 2009 Feb;4(2):361-8.

Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, Leehey DJ, McCullough PA, O'Connor T, Palevsky PM, Reilly RF, Seliger SL, Warren SR, Watnick S, Peduzzi P, Guarino P; VA NEPHRON-D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013 Nov 14;369(20):1892-903.

Chen SS, Seliger SL, Fried LF. Complete inhibition of the renin-angiotensin-aldosterone system; where do we stand? Curr Opin Nephrol Hypertens. 2014 Sep;23(5):449-55.

Zimering MB, Zhang JH, Guarino PD, Emanuele N, McCullough PA, Fried LF; Investigators for the VA NEPHRON-D. Endothelial cell autoantibodies in predicting declining renal function, end-stage renal disease, or death in adult type 2 diabetic nephropathy. Front Endocrinol (Lausanne). 2014 Aug 11;5:128.

More Information

• Study ClinicalTrails.gov site
• ClinicalTrials.gov Identifier: NCT00555217
• Dimensions for VA summary (Requires an account to access outside the VA network. Dimensions for VA is a database that connects publications, grants, patents, clinical trials, and policy documents)