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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01667614
• Other study ID #: 90-2-27-16-10
• Status: Completed
• Phase: Phase 2
• First received: August 15, 2012
• Last updated: August 27, 2012
• Start date: May 2010
• Est. completion date: July 2012

Study information

• Verified date: August 2012
• Source: Tehran University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: July 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Diabetic Nephropathy
• Essential Hypertension
• Hypertension
• Kidney Diseases
• Type 2 Diabetes Mellitus

Intervention

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

Locations

Country	Name	City	State
Iran, Islamic Republic of	Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary albumin excretion	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.	18 months	No
Secondary	estimated glomerular filtration rate	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.	18 months	No
Secondary	Blood pressure	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.	18 months	No
Secondary	serum creatinine concentrations	serum creatinine concentrations assessed by Jaffe method. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.	18 months	No
Secondary	Serum potassium concentrations	Serum potassium concentrations measured at baseline, 1st month, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.	18 months	Yes