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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Diabetic Nephropathy; Essential Hypertension
• Intervention / Treatment: Drug: spironolacone 25 mg tablets added to losartan

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 13145-784
    • Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Alireza Esteghamati, M.D., Tehran University Of Medical Sciences

Publications and helpful links

General Publications

• Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: August 15, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (Estimate): August 17, 2012

Study Record Updates

• Last Update Posted (Estimate): August 28, 2012
• Last Update Submitted That Met QC Criteria: August 27, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Hypertension; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies; Essential Hypertension; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 90-2-27-16-10