Efficacy of ACE Inhibitors, MRAs and ACE Inhibitor/ MRA Combination

Study Overview
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Brief Summary
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The aim of our work is to compare the antiproteinuric efficacy of ACEI monotherapy, Selective MRA monotherapy and their combination in mildly hypertensive patients with type 2 diabetes mellitus and microalbuminuria

Detailed Description
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Diabetic nephropathy (DN) is the most common cause renal failure in Western countries, responsible for 45% of patients on renal replacement therapy.Diabetic nephropathy was characterized in the early stage by increased albumin excretion in urine, known as microalbuminuria. (DN) results from interactions between different pathological factors that include hyperglycemia, increased activity of the renin-angiotensin-aldosterone-system (RAAS), uncontrolled high systemic and glomerular pressure . (DN) optimal therapy continues to evolve. The main lines of treatment include strict glycemic and blood pressure (BP) control. The angiotensin converting enzyme (ACE) inhibitors have been known to reduce proteinuria both in normotensive and hypertensive patients with diabetic nephropathy and in hypertensive individuals with end stage renal failure . The mechanism by which ACE inhibitors exert their effect on proteinuria reduction is still unknown. The control of high systemic arterial pressure can be beneficial by reducing the filtration pressure. However, no association has been found between antihypertensive effect and proteinuria reduction in several studies. Microalbuminuria which is an early sign of nephropathy can be decreased also by use of Angiotensin receptor blockers (ARBs) in patients with type 2 diabetes mellitus . Insufficient blockade of aldosterone may lead to inadequate anti-albuminuric effects. Studies show that renin-angiotensin-aldosterone system inhibition with ACEI/ARB alone sometimes does not achieve optimal renoprotective effects and does not reduce progression of renal disease, despite therapy. Addition of mineralocorticoid receptor antagonists (MRAs) to angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy was found to reduce proteinuria in patients diabetic nephropathy and can delay progression of renal dysfunction.

Official Title
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Antiproteinuric Efficacy of ACE Inhibitors, Selective MRAs and ACE Inhibitor/Selective MRA Combination Therapy in Diabetic Hypertensives With Microalbuminuria

Conditions
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Diabetic Nephropathy Type 2, Microalbuminuria Due to Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Tritace (Ramipril 10 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and non-pregnant female patients with established diagnosis of type 2 DM at least five years ago with glycosylated hemoglobin (HbA1c) ≤ 8.5% Age 30-80 Y Stage 1 hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) and microalbuminuria diagnosed by measuring Urinary albumin/creatinine ratio (UACR) . Microalbuminuria was defined at a level between (30-300 mg/g) Patients included in our study had never been treated with ACEIs, ARBs or aldosterone antagonists, serum potassium level ≥ 3.5 and ≤ 5.0 mmol/L before randomization with estimated glomerular filtration rate (e GFR) ≥50 mL/min/1.73 m2 Exclusion Criteria: Patients with type 1 diabetes mellitus Patients with BP ≥ 160/100 mmHg Patients with secondary hypertension Non-diabetic nephropathy including (chronic glomerulonephritis, polycystic kidney disease and nephrosclerosis), Confirmed bilateral renal artery stenosis or stenosis of the renal artery in solitary functioning kidney History of New York Heart Association functional class III and IV heart failure Patients with rapid progression of kidney disease and women who were pregnant, breast-feeding, or planning to become pregnant during the study period

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three parallel groups of therapy; Ramipril 10 mg monotherapy (25 patients) ,Eplerenone 50 mg monotherapy (25 patients) and combination therapy of Eplernone/Ramipril 50/10 mg (25 patients)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tritace (Ramipril)<br>25 patients with type 2 diabetes mellitus and mild hypertension will be randomized to Tritace (Ramipril) 10 mg/ day. Full doses will be reached by forced titration after 4 weeks | Drug: Tritace (Ramipril 10 mg)<br>* Stratified randomized clinical trial<br>* Other names: Tritace/ Eraloner (Ramipril 10 mg/ Eplerenone 50 mg);|
| Active Comparator: Eraloner (Eplerenone)<br>25 patients with type 2 diabetes mellitus and mild hypertension will be randomized to Eraloner (Eplerenone) 50 mg/ day. Full doses will be reached by forced titration after 4 weeks | Drug: Tritace (Ramipril 10 mg)<br>* Stratified randomized clinical trial<br>* Other names: Tritace/ Eraloner (Ramipril 10 mg/ Eplerenone 50 mg);|
| Active Comparator: Tritace/Eraloner (Ramipril/Eplerenone)combination therapy<br>25 patients with type 2 diabetes mellitus and mild hypertension will be randomized to Tritace/Eraloner (Ramipril 10 mg / Eplerenone 50 mg ) / day. Full doses will be reached by forced titration after 4 weeks | Drug: Tritace (Ramipril 10 mg)<br>* Stratified randomized clinical trial<br>* Other names: Tritace/ Eraloner (Ramipril 10 mg/ Eplerenone 50 mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary albumin/creatinin ratio (UACR) | Percentage change in albumin/creatinin ratio compared with the baseline value | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | change in blood pressure level | 24 weeks | 
| estimated Glomerular Filtration Rate (e GFR) | change in estimated Glomerular Filtration Rate (e GFR) | 24 weeks | 
| Serum K | change in serum K level | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microalbuminuria, Diabetic nephropathy, Hperkalemia, Eplerenone, Ramipril