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

This study has been completed.
Information provided by (Responsible Party):
Alireza Esteghamati, Tehran University of Medical Sciences Identifier:
First received: August 15, 2012
Last updated: August 27, 2012
Last verified: August 2012
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.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Diabetic Nephropathy
Essential Hypertension
Drug: spironolacone 25 mg tablets added to losartan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome 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 Outcome 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.

Enrollment: 136
Study Start Date: May 2010
Study Completion Date: July 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: spironolacone 25 mg tablets added to losartan
spironolactone 25 mg once daily added to losartan


Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01667614

Iran, Islamic Republic of
Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center
Tehran, Iran, Islamic Republic of, 13145-784
Sponsors and Collaborators
Tehran University of Medical Sciences
Principal Investigator: Alireza Esteghamati, M.D. Tehran University of Medical Sciences
  More Information

Responsible Party: Alireza Esteghamati, Professor Alireza Esteghamati, Tehran University of Medical Sciences Identifier: NCT01667614     History of Changes
Other Study ID Numbers: 90-2-27-16-10
Study First Received: August 15, 2012
Last Updated: August 27, 2012

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Diabetic Nephropathies
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents processed this record on May 24, 2017