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

Tehran University of Medical Sciences

Status and phase: Completed; Phase 2

Conditions: Diabetic Nephropathy; Type 2 Diabetes Mellitus; Essential Hypertension

Treatments: Drug: spironolacone 25 mg tablets added to losartan

Study type: Interventional

Funder types: Other

Identifiers

NCT01667614

90-2-27-16-10

Details and patient eligibility

About

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.

Enrollment: 136 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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136 participants in 2 patient groups

ACE/ARB

No Intervention group

Description:

In 62 patients previously treated with enalapril (10-30 mg daily) + losartan (50-100 mg daily), this regimen was continued.

Spironolactone/ARB

Active Comparator group

Description:

spironolacone 25 mg tablets added to losartan

Treatment:

Drug: spironolacone 25 mg tablets added to losartan