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

Phase 2
Completed
Conditions
Type 2 Diabetes Mellitus
Diabetic Nephropathy
Essential Hypertension
Interventions
Drug: spironolacone 25 mg tablets added to losartan
Registration Number
NCT01667614
Lead Sponsor
Tehran University of Medical Sciences
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
136
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Spironolactone/ARBspironolacone 25 mg tablets added to losartanspironolacone 25 mg tablets added to losartan
Primary Outcome Measures
NameTimeMethod
Urinary albumin excretion18 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
NameTimeMethod
estimated glomerular filtration rate18 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 pressure18 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 concentrations18 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 concentrations18 months

Serum potassium concentrations measured at baseline, 1st month, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.

Trial Locations

Locations (1)

Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center

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Tehran, Iran, Islamic Republic of

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