Early Nephropathy Study in Diabetes With Inhibitory Renin-Angiotensin-Aldosterone System Therapy (END-IT)
Overview
- Phase
- Not Applicable
- Intervention
- benazepril
- Conditions
- Microalbuminuria
- Sponsor
- Charles Drew University of Medicine and Science
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Microalbuminuria Reported as Urinary Albumin:Creatinine Ratio
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
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]).
Detailed Description
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.
Investigators
Mayer Davidson
Professor of Medicine
Charles Drew University of Medicine and Science
Eligibility Criteria
Inclusion Criteria
- •Males and females, age 18-70
- •Subjects with diabetic renal disease as defined by spot urine albumin - creatinine ratio 30-300mg/g and estimated glomerular filtration rate of \>60 ml/min
Exclusion Criteria
- •Intake of non-steroidal anti-inflammatory agents (NSAIDs) more than 15 days/month, excluding aspirin.
- •Inability to discontinue NSAIDs or aspirin for 5 days prior to GFR measurement.
- •History of severe adverse reaction to any of the randomized drugs required for use in the protocol or contraindication of their use.
- •Participation in another intervention study.
- •Pregnancy or likelihood of becoming pregnant during the study period; lactation
- •Clinical and laboratory evidence of any renal disease other than diabetic nephropathy.
- •History of drug abuse in the past 2 years, including narcotics, cocaine or alcohol (\> 21 drinks per week). Serious systemic disease that might influence survival or the course of renal disease. (Chronic oral steroid therapy is exclusion, but steroid-containing nasal sprays are not. Inactive sarcoidosis is not an exclusion).
- •History of malignant or accelerated hypertension within 6 months prior to study entry; previous chronic peritoneal or hemodialysis or renal transplantation. Known secondary causes of hypertension. Spot urine albumin - creatinine ratio exceeding 300 (mg/g)
- •Serum potassium level \> 5.5 mEq/L for those not on ACE inhibitors during Baseline, or serum potassium level \> 5.9 mEq/L for those on ACE inhibitors during Baseline.
- •Leukopenia \< 2,500/mm3 at screening and confirmed at the end of Baseline.
Arms & Interventions
Low dose inhibition of RAS
Standard low dose inhibition of the RAS with 10 mg of benazepril orally daily to treat microalbuminuria
Intervention: benazepril
Agressive inhibition of the RAS
40-80 mg benazepril plus 25-100 mg losartan both orally once or twice daily
Intervention: benazepril
Outcomes
Primary Outcomes
Microalbuminuria Reported as Urinary Albumin:Creatinine Ratio
Time Frame: 3 to 36 months
Average of ratio for all participants during the 3-36 months of the study
Secondary Outcomes
- Estimated Glomerular Filtration Rate(3 to 36 months)
- Carotid Artery Intima Thickness(6 to 36 months)
- Endothelial Dysfunction(6 to 36 months)