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

Phase 2

• Conditions: Diabetic Nephropathy Type 2; Microalbuminuria Due to Type 2 Diabetes Mellitus
• Interventions: Drug: Tritace (Ramipril 10 mg)

• Registration Number: NCT04143412
• Lead Sponsor: Beni-Suef University

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-02-04
• Study First Submitted: 2019-10-26
• Study First Submitted QC: 2019-10-26
• Study First Posted: 2019-10-29
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-14
• Last Update Posted: 2020-01-18
• Primary Completion: 2020-02
• Study Completion: 2020-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 75

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eraloner (Eplerenone)	Tritace (Ramipril 10 mg)	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
Tritace (Ramipril)	Tritace (Ramipril 10 mg)	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
Tritace/Eraloner (Ramipril/Eplerenone)combination therapy	Tritace (Ramipril 10 mg)	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

Primary Outcome Measures

Name	Time	Method
Urinary albumin/creatinin ratio (UACR)	24 weeks	Percentage change in albumin/creatinin ratio compared with the baseline value

Secondary Outcome Measures

Name	Time	Method
Blood pressure	24 weeks	change in blood pressure level
estimated Glomerular Filtration Rate (e GFR)	24 weeks	change in estimated Glomerular Filtration Rate (e GFR)
Serum K	24 weeks	change in serum K level

Trial Locations

Locations (1)

Faculty of Medicine,Beni-Suef University; 🇪🇬 Banī Suwayf, Egypt