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Low Dose Versus Aggressive Inhibition of the Renin-Angiotensin-Aldosterone (RAS) to Treat Microalbuminuria (END-IT)

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ClinicalTrials.gov Identifier: NCT00907374
Recruitment Status : Completed
First Posted : May 22, 2009
Results First Posted : March 30, 2012
Last Update Posted : March 30, 2012
Sponsor:
Information provided by (Responsible Party):
Mayer Davidson, Charles Drew University of Medicine and Science

Tracking Information
First Submitted Date  ICMJE May 21, 2009
First Posted Date  ICMJE May 22, 2009
Results First Submitted Date  ICMJE February 9, 2012
Results First Posted Date  ICMJE March 30, 2012
Last Update Posted Date March 30, 2012
Study Start Date  ICMJE July 2005
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2012)
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 21, 2009)
Microalbuminuria [ Time Frame: 3 to 36 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2012)
  • Estimated Glomerular Filtration Rate [ Time Frame: 3 to 36 months ]
    This is an average for all participants during the 3-36 month study period
  • Carotid Artery Intima Thickness [ Time Frame: 6 to 36 months ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2009)
  • eGFR [ Time Frame: 3 to 36 months ]
  • Carotid Artery Intima Thickness [ Time Frame: 6 to 36 months ]
  • Endothelial Dysfunction [ Time Frame: 6 to 36 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Versus Aggressive Inhibition of the Renin-Angiotensin-Aldosterone (RAS) to Treat Microalbuminuria
Official Title  ICMJE Early Nephropathy Study in Diabetes With Inhibitory Renin-Angiotensin-Aldosterone System Therapy (END-IT)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Microalbuminuria
Intervention  ICMJE
  • Drug: benazepril
    benazepril 10 mg orally once daily
    Other Name: Lotensin
  • Drug: benazepril
    40-80 mg benazepril plus 25-100 mg losartan orally once or twice daily
    Other Names:
    • Lotensin
    • Cozaar
Study Arms  ICMJE
  • Active Comparator: Low dose inhibition of RAS
    Standard low dose inhibition of the RAS with 10 mg of benazepril orally daily to treat microalbuminuria
    Intervention: Drug: benazepril
  • Experimental: Agressive inhibition of the RAS
    40-80 mg benazepril plus 25-100 mg losartan both orally once or twice daily
    Intervention: Drug: benazepril
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 21, 2009)
46
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

  • Doubt that the participant will be able to adhere to medications or comply with the protocol visit schedule
  • Arm Circumference > 52 cm, which precludes measuring blood pressure with the "thigh" blood pressure cuff. Arm length such that if the cuff circumference extended into the antecubital space so that the cuff interfered with placement of the stethoscope over the brachial artery for blood pressure measurement
  • Clinical evidence of lead intoxication. Clinical evidence of congestive heart failure, current or within the preceding six months. Ejection fraction below 35% measured by any method. Heart block greater than first degree or any other arrhythmia that contraindicated the use of any of the primary BP drugs.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00907374
Other Study ID Numbers  ICMJE IRB# 04-09-772
U54RR014616 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayer Davidson, Charles Drew University of Medicine and Science
Study Sponsor  ICMJE Charles Drew University of Medicine and Science
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Naureen Taureen, MD Charles Drew University
Study Director: Mayer B. Davidson, MD Charles Drew University
PRS Account Charles Drew University of Medicine and Science
Verification Date March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP