Effects of Spironolactone Combination Therapy on Proteinuria, Kidney Function, and Blood Pressure
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Purpose
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 Endpoint Classification: Safety/Efficacy Study 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 |
- Urinary albumin excretion [ Time Frame: 18 months ] [ Designated as safety issue: No ]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.
- estimated glomerular filtration rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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
|
Eligibility| Ages Eligible for Study: | 40 Years to 80 Years |
| Genders Eligible for Study: | Both |
| 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
Contacts and Locations| Iran, Islamic Republic of | |
| Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center | |
| Tehran, Iran, Islamic Republic of, 13145-784 | |
| Principal Investigator: | Alireza Esteghamati, M.D. | Tehran University of Medical Sciences |
More Information
No publications provided
| Responsible Party: | Alireza Esteghamati, Professor Alireza Esteghamati, Tehran University of Medical Sciences |
| ClinicalTrials.gov 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 |
| Health Authority: | Iran: Ministry of Health |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Diabetic Nephropathies Hypertension Kidney Diseases Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Urologic Diseases Diabetes Complications Vascular Diseases Cardiovascular Diseases Spironolactone Losartan |
Aldosterone Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Diuretics Natriuretic Agents Cardiovascular Agents Therapeutic Uses Anti-Arrhythmia Agents Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013