Clinical trial NCT01667614: Effects of Spironolactone Combination Therapy on Proteinuria, Kidney Function, and Blood Pressure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Diabetic Nephropathy
Essential Hypertension
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2012-08-17
Enrollment: 136
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Urinary albumin excretion
timeFrame: 18 months
Secondary outcomes:
measure: estimated glomerular filtration rate
timeFrame: 18 months
measure: Blood pressure
timeFrame: 18 months
measure: serum creatinine concentrations
timeFrame: 18 months
measure: Serum potassium concentrations
timeFrame: 18 months
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center
Study officials:
affiliation: Tehran University of Medical Sciences
name: Alireza Esteghamati, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.