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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alireza Esteghamati, Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01667614
First received: August 15, 2012
Last updated: August 27, 2012
Last verified: August 2012
  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

Resource links provided by NLM:


Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01667614

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
Sponsors and Collaborators
Tehran University of Medical Sciences
Investigators
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
Cardiovascular Diseases
Diabetes Complications
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Urologic Diseases
Vascular Diseases
Losartan
Spironolactone
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014