NCT00555217|TerminatedPhase 3ResultsDMC
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It was stopped primarily because of safety concerns along with low conditional power to detect a treatment effect on the primary outcome.
VA NEPHRON-D
CSP #565 - Combination Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D Study)
Sponsor study identifier
interventional
1,448
2 countries
31
Study Start
July 2008
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
September 2014
Actual (reported)Study Completion
October 2014
Actual (reported)Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States. The overall rate of ESRD secondary to diabetes has risen 68% since 1992. Medications that block the renin angiotensin system have been shown to decrease the progression of diabetic nephropathy. The use of an angiotensin receptor blocker (ARB) has been shown to decrease the risk of progression of kidney disease in two studies of individuals with Type 2 diabetes and proteinuria. Despite the use of an ARB, the incidence of renal failure remained high in the treated group in both studies. The combination of an angiotensin converting enzyme inhibitor (ACEI) and ARB can lead to more complete blockade of the renin angiotensin system. In diabetic kidney disease, combination therapy has been shown to decrease proteinuria in short-term studies. Although there are encouraging results for improvement in proteinuria there are no data on progression of kidney disease for the use of combination of ACEI and ARB therapy in patients with diabetes. In addition, there could be an increased risk of serious hyperkalemia in individuals with diabetes who receive combination ACEI and ARB. The investigators therefore propose a randomized double blind multi-center clinical trial to assess the effect of combination of ACEI and ARB in patients with diabetes and proteinuria on progression of kidney disease.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
October 2014
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
November 7, 2007
Actual (reported)November 8, 2007
Actual (reported)July 2008
Date type not reportedThis date has not been verified as actual or estimated.
September 2014
Actual (reported)October 2014
Actual (reported)May 29, 2015
Actual (reported)A Composite Endpoint of Reduction in Estimated GFR of 30ml/Min/1.73m*m in Individuals w/a Baseline Estimated GFR >= 60 ml/Min/1.73m*m, Reduction in Estimated GFR >50% in Individuals w/ Baseline Estimated GFR <60ml/Min/1.73m*m; ESRD or Death
Time to the first event of reduction in estimated GFR of 30ml/min/1.73m\*m in individuals w/a baseline estimated GFR \>= 60 ml/min/1.73m\*m, reduction in estimated GFR \>50% in individuals w/ baseline estimated GFR \<60ml/min/1.73m\*m; ESRD or death.
From enrollemnt to time of first primary event, up to 4.5 years
A Renal Composite Endpoint, Defined as; Reduction in Estimated GFR of >50% (for Individuals With Baseline GFR <60) or Reduction in GFR of >30 (for Individuals With Baseline GFR >= GFR 60) or ESRD.
From enrollment to time of first event, up to 4.5 years
Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)
Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)
50 or 100mg/day
10, 20 or 40 mg/day
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Carl T. Hayden VA Medical Center
Phoenix, Arizona, 85012, United States
Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
Little Rock, Arkansas, 72205-5484, United States
VA Medical Center, Loma Linda
Loma Linda, California, 92357, United States
VA Palo Alto Health Care System
Palo Alto, California, 94304-1290, United States
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, 06516, United States
North Florida/South Georgia Veterans Health System
Gainesville, Florida, 32608, United States
VA Medical Center, Miami
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. doi: 10.2215/CJN.03350708. Epub 2008 Dec 31.
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. doi: 10.1056/NEJMoa1303154. Epub 2013 Nov 9.
In October, 2012 the DMC recommended that study treatment be stopped primarily because of safety concerns along with low conditional power to detect a treatment effect on the primary outcome.
Linda Fried, MD MPH
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
1,448 participants (actual enrollment reported by the registry).
First Submitted
November 7, 2007
First Posted
November 8, 2007
Study Start
July 2008
Date type not reportedThis date has not been verified as actual or estimated.
Contact the study team to confirm eligibility.
Miami, Florida, 33125, United States
James A. Haley Veterans Hospital, Tampa
Tampa, Florida, 33612, United States
Edward Hines, Jr. VA Hospital
Hines, Illinois, 60141-5000, United States
Richard Roudebush VA Medical Center, Indianapolis
Indianapolis, Indiana, 46202-2884, United States
VA Medical Center, Iowa City
Iowa City, Iowa, 52246-2208, United States
VA Maryland Health Care System, Baltimore
Baltimore, Maryland, 21201, United States
VA Medical Center, Minneapolis
Minneapolis, Minnesota, 55417, United States
VA Medical Center, Kansas City MO
Kansas City, Missouri, 64128, United States
VA Medical Center, St Louis
St Louis, Missouri, 63106, United States
VA Medical Center, Omaha
Omaha, Nebraska, 68105-1873, United States
VA New Jersey Health Care System, East Orange
East Orange, New Jersey, 07018, United States
New Mexico VA Health Care System, Albuquerque
Albuquerque, New Mexico, 87108-5153, United States
VA Western New York Healthcare System at Buffalo
Buffalo, New York, 14215, United States
VA Medical Center, Durham
Durham, North Carolina, 27705, United States
VA Medical Center, Cleveland
Cleveland, Ohio, 44106, United States
VA Medical Center, Portland
Portland, Oregon, 97201, United States
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240, United States
Ralph H Johnson VA Medical Center, Charleston
Charleston, South Carolina, 29401-5799, United States
WJB Dorn Veterans Hospital, Columbia
Columbia, South Carolina, 29209, United States
VA Medical Center, Memphis
Memphis, Tennessee, 38104, United States
VA Medical Center
Nashville, Tennessee, 37212-2637, United States
VA North Texas Health Care System, Dallas
Dallas, Texas, 75216, United States
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, 23249, United States
Zablocki VA Medical Center, Milwaukee
Milwaukee, Wisconsin, 53295-1000, United States
VA Medical Center, San Juan
San Juan, 00921, Puerto Rico
Fried LF, Emanuele N, Zhang JH. Combined angiotensin inhibition in diabetic nephropathy. N Engl J Med. 2014 Feb 20;370(8):779. doi: 10.1056/NEJMc1315504. No abstract available.
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. doi: 10.1097/MNH.0000000000000043.
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. doi: 10.3389/fendo.2014.00128. eCollection 2014.
Tamargo CL, Coca SG, Thiessen Philbrook H, Hu DG, Ix JH, Shlipak MG, Fried LF, Gutierrez OM, Waikar SS, Schrauben SJ, Schelling JR, Ganz P, Kimmel PL, Greenberg JH, Deo R, Takakura A, Vasan RS, Bonventre JV, Parikh CR. The distal nephron biomarkers associate with diabetic kidney disease progression. JCI Insight. 2025 Jun 23;10(12):e186836. doi: 10.1172/jci.insight.186836. eCollection 2025 Jun 23.
Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.
Huang Y, Fried LF, Kyriakides TC, Johnson GR, Chiu S, Mcdonald L, Zhang JH. Automated safety event monitoring using electronic medical records in a clinical trial setting: Validation study using the VA NEPHRON-D trial. Clin Trials. 2019 Feb;16(1):81-89. doi: 10.1177/1740774518813121. Epub 2018 Nov 16.
Primary Completion
September 2014
Actual (reported)Study Completion
October 2014
Actual (reported)Last Updated
May 29, 2015
Results First Posted
May 29, 2015
Record last verified: 2015-05
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Source: ClinicalTrials.gov.
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