Effects of Spironolactone Combination Therapy on Proteinuria, Kidney Function, and Blood Pressure

Overview

The detrimental effects of aldostrone are not adequately arrested by the use of angiotensin converting enzyme (ACE), angiotensin II receptor blocker (ARB) or a combination of both. Recent evidence has provided robust evidence that aldostrone escape plays an important role in this regard. It is believed that aldostrone escape occurs quite commonly with reports indicating prevalence rates as high as 22% with ARBs and 40% with ACE inhibitors. In a trial of patients with diabetes and hypertension it was shown that treatment of aldostrone escape with spironolactone 25 mg daily for three months significantly reduces proteinuria. A number of other trials have similarly observed that addition of spironolactone to an ACE inhibitor based regimen provides additional benefits on proteinuria reduction, blood pressure control, and prevention of glomerular filtration rate (GFR) decline. Most of the available trials in this regard are of short duration (e.g. three months), and have added spironolactone to an ACE or ACE+ARB based regimen (the so-called triple blockade). Currently, evidence evaluating efficacy of a combined ARB+spironolactone regimen compared with conventional double RAS blockade (i.e. ACE+ARB) is lacking. Hence, this randomized open label trial was initiated to determine the effects of addition of spironolactone 25 mg daily to losartan over a period of 18 months.

Full Title of Study: “Comparison of Efficacy of Losartan/Spironolactone and Losartan/Enalapril on Urinary Albumin Excretion, Estimated Glomerular Filtration Rate, and Blood Pressure in Patients With Type 2 Diabetes Nephropathy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2012

Interventions

  • Drug: spironolacone 25 mg tablets added to losartan
    • spironolactone 25 mg once daily added to losartan

Arms, Groups and Cohorts

  • No Intervention: ACE/ARB
    • In 62 patients previously treated with enalapril (10-30 mg daily) + losartan (50-100 mg daily), this regimen was continued.
  • Active Comparator: Spironolactone/ARB
    • spironolacone 25 mg tablets added to losartan

Clinical Trial Outcome Measures

Primary Measures

  • Urinary albumin excretion
    • Time Frame: 18 months
    • Urinary albumin excretion assessed by overnight (12 hour) collection of urine. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.

Secondary Measures

  • estimated glomerular filtration rate
    • Time Frame: 18 months
    • estimated glomerular filtration rate calculated using the formula developed by Chronic Kidney Disease Epidemiology Collaboration. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
  • Blood pressure
    • Time Frame: 18 months
    • Systolic and diastolic blood pressure assessed by mercury sphygnomanometry. Patients were placed in a sitting position and after ten minutes rest, two readings from right-side hand with five minutes interval were obtained. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
  • serum creatinine concentrations
    • Time Frame: 18 months
    • serum creatinine concentrations assessed by Jaffe method. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
  • Serum potassium concentrations
    • Time Frame: 18 months
    • Serum potassium concentrations measured at baseline, 1st month, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.

Participating in This Clinical Trial

Inclusion Criteria

  • type 2 diabetes patients with diabetic nephropathy in the range of micro- or macroalbuminuria – treatment with combination of enalapril and losartan for more than one year Exclusion Criteria:

  • history of non-adherence to prescribed medication assessed by the prescribing physician – baseline potassium > 5.5 meq/L – chronic kidney disease stages 4 or 5 – history or evidence of non-diabetic kidney disease

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Tehran University of Medical Sciences
  • Provider of Information About this Clinical Study
    • Principal Investigator: Alireza Esteghamati, Professor Alireza Esteghamati – Tehran University of Medical Sciences
  • Overall Official(s)
    • Alireza Esteghamati, M.D., Principal Investigator, Tehran University of Medical Sciences

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