Low Dose Versus Aggressive Inhibition of the Renin-Angiotensin-Aldosterone (RAS) to Treat Microalbuminuria (END-IT)
The objective of the study is to assess the effect of standard versus aggressive inhibition of the renin-angiotensin system (RAS)in type 2 diabetic patients with microalbuminuria (MA) on; a)progression of microalbuminuria, b)estimated glomerular filtration rate (eGFR), c)endothelial dysfunction (measured by post-hyperemia arterial tonometry) and d)the slowing of the progression of atherosclerotic disease (measured by carotid intima media thickness [CIMT]).
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Early Nephropathy Study in Diabetes With Inhibitory Renin-Angiotensin-Aldosterone System Therapy (END-IT)|
- Microalbuminuria Reported as Urinary Albumin:Creatinine Ratio [ Time Frame: 3 to 36 months ] [ Designated as safety issue: No ]Average of ratio for all participants during the 3-36 months of the study
- Estimated Glomerular Filtration Rate [ Time Frame: 3 to 36 months ] [ Designated as safety issue: No ]This is an average for all participants during the 3-36 month study period
- Carotid Artery Intima Thickness [ Time Frame: 6 to 36 months ] [ Designated as safety issue: No ]Thickness of intima of right carotid artery; average of all particpants from 6-36 months of study
- Endothelial Dysfunction [ Time Frame: 6 to 36 months ] [ Designated as safety issue: No ]Post hyperemia increase in blood flow - fold increase from before and after occluding BP; values are mean of all participants in 6-36 months of study period.
|Study Start Date:||July 2005|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Active Comparator: Low dose inhibition of RAS
Standard low dose inhibition of the RAS with 10 mg of benazepril orally daily to treat microalbuminuria
benazepril 10 mg orally once daily
Other Name: Lotensin
Experimental: Agressive inhibition of the RAS
40-80 mg benazepril plus 25-100 mg losartan both orally once or twice daily
40-80 mg benazepril plus 25-100 mg losartan orally once or twice daily
Diabetic patients with confirmed MA (50-300 mg albumin per g creatinine) on a morning spot urine sample were entered into a one to three month run-in phase before randomization. (50 mg/g was used as the lower limit to allow room for improvement to reach normal.) Since hypertension and uncontrolled hyperglycemia will cause MA, blood pressure (BP) and hemoglobin A1c (AIC) levels were reduced to <130/80 mm Hg and <8.0%, respectively, during this period. All patients had been on various doses of an angiotensin converting enzyme inhibitor (ACE-I) which were reduced to 10 mg benazepril and BP controlled with other classes of anti-hypertensive drugs (except for angiotensin receptor blockers [ARB's]). Glycemia was treated with intensification of their current therapy. MA and BP were measured monthly.
When goal levels of BP and AIC were achieved and MA was still present, patients were randomized to either low dose RAS inhibition (10 mg benazepril) (Standard) or aggressive inhibition of the RAS (Aggressive). MA continued to be measured monthly and the progressive increase in doses of an ACE-I and an ARB was as follows. Benazepril (the ACE-I) - 10 mg to 20 mg to 40 mg to adding losartan (the ARB) -25 mg to 50 mg to 100 mg to increasing benazepril to 80 mg with the goal of returning albumin excretion to normal. Other classes of drugs were reduced as necessary to keep systolic BP > 100 mm Hg. Serum creatinine and potassium[K+] were measured monthly, AIC levels every 3 months and CIMT by ultrasound and endothelial function by post hyperemia and nitroglycerine (NTG) - induced peripheral artery tonometry (PAT) via finger plethysmography every six months.
|United States, California|
|Charles Drew University|
|Los Angeles, California, United States, 90059|
|Principal Investigator:||Naureen Taureen, MD||Charles Drew University|
|Study Director:||Mayer B. Davidson, MD||Charles Drew University|