Diabetic Nephropathy Type 2Phase 2NCT04143412
Efficacy of ACE Inhibitors, MRAs and ACE Inhibitor/ MRA Combination
A Phase 2 study testing Tritace (Ramipril 10 mg) in people with Diabetic Nephropathy Type 2 and Microalbuminuria Due to Type 2 Diabetes Mellitus, run by Beni-Suef University at 1 site in Egypt.
Trial 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 Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Diabetic Nephropathy Type 2, Microalbuminuria Due to Type 2 Diabetes Mellitus
- What is being tested?
- Tritace (Ramipril 10 mg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteEgypt
- Study dates
- 4 Feb 2019to Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Faculty of Medicine,Beni-Suef University
Banī Suwayf, 62511
Mostafa O El Mokadem, M.D., +201009414408, mostafa.elmokadem9@med.bsu.edu.eg
Yasser A Abd el Hady, M.D., +201001775524, Yasser.abdelhady@icloud.com
About this study
Official title: Antiproteinuric Efficacy of ACE Inhibitors, Selective MRAs and ACE Inhibitor/Selective MRA Combination Therapy in Diabetic Hypertensives With Microalbuminuria
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
Read the 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.
- Being tested
- Tritace (Ramipril 10 mg)
- Keywords
- microalbuminuria, Diabetic nephropathy, Hperkalemia, Eplerenone, Ramipril
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tritace (Ramipril 10 mg)Drug
Also called Eraloner (Eplerenone 50 mg), Tritace/ Eraloner (Ramipril 10 mg/ Eplerenone 50 mg)
Stratified randomized clinical trial
| Study group | Role | What they receive |
|---|---|---|
| Tritace (Ramipril) | Active comparator | 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 Receives: Drug: Tritace (Ramipril 10 mg) |
| Eraloner (Eplerenone) | Active comparator | 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 Receives: Drug: Tritace (Ramipril 10 mg) |
| Tritace/Eraloner (Ramipril/Eplerenone)combination therapy | Active comparator | 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 Receives: Drug: Tritace (Ramipril 10 mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary albumin/creatinin ratio (UACR)
Percentage change in albumin/creatinin ratio compared with the baseline value
Measured: 24 weeks
Secondary outcomes (3)
Blood pressure
change in blood pressure level
Measured: 24 weeks
estimated Glomerular Filtration Rate (e GFR)
change in estimated Glomerular Filtration Rate (e GFR)
Measured: 24 weeks
Serum K
change in serum K level
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start4 Feb 2019
- Primary completionFeb 2020 (estimated)
- Study completionMar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Diabetic Nephropathy Type 2Studies of the same condition, open and under way.
- More trials run by Beni-Suef UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beni-Suef University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mostafa El Mokadem, Beni-Suef University
- Investigators
- Mostafa O El Mokadem, M.D., Principal investigator, Cardiology department,Faculty of Medicine, Beni-Suef University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04143412
- Sponsor's protocol ID
- RAAS blockers in albuminuria
- Status last verified
- Jan 2020
- First submitted
- 26 Oct 2019
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To respect privacy and confidentiality of our patients
Publications
Espinel E, Agraz I, Ibernon M, Ramos N, Fort J, Seron D. Renal Biopsy in Type 2 Diabetic Patients. J Clin Med. 2015 May 18;4(5):998-1009. doi: 10.3390/jcm4050998.
PubMed 26239461Zelmanovitz T, Gerchman F, Balthazar AP, Thomazelli FC, Matos JD, Canani LH. Diabetic nephropathy. Diabetol Metab Syndr. 2009 Sep 21;1(1):10. doi: 10.1186/1758-5996-1-10.
PubMed 19825147Cao Z, Cooper ME. Pathogenesis of diabetic nephropathy. J Diabetes Investig. 2011 Aug 2;2(4):243-7. doi: 10.1111/j.2040-1124.2011.00131.x.
PubMed 24843491Satirapoj B, Adler SG. Prevalence and Management of Diabetic Nephropathy in Western Countries. Kidney Dis (Basel). 2015 May;1(1):61-70. doi: 10.1159/000382028. Epub 2015 May 1.
PubMed 27536666Jalal S, Sofi FA, Abass SM, Alai MS, Bhat MA, Rather HA, Lone NA, Siddiqi MA. Effect of amlodipine and lisinopril on microalbuminuria in patients with essential hypertension: A prospective study. Indian J Nephrol. 2010 Jan;20(1):15-20. doi: 10.4103/0971-4065.62090.
PubMed 20535265Galle J. Reduction of proteinuria with angiotensin receptor blockers. Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S36-43. doi: 10.1038/ncpcardio0806.
PubMed 18580865Cagnoni F, Njwe CA, Zaninelli A, Ricci AR, Daffra D, D'Ospina A, Preti P, Destro M. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination. Vasc Health Risk Manag. 2010 Aug 9;6:549-59. doi: 10.2147/vhrm.s11816.
PubMed 20730071Cooper LB, Lippmann SJ, Greiner MA, Sharma A, Kelly JP, Fonarow GC, Yancy CW, Heidenreich PA, Hernandez AF. Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease. J Am Heart Assoc. 2017 Dec 23;6(12):e006540. doi: 10.1161/JAHA.117.006540.
PubMed 29275368
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiproteinuric Efficacy of ACE Inhibitors, Selective MRAs and ACE Inhibitor/Selective MRA Combination Therapy in Diabetic Hypertensives With Microalbuminuria
- ClinicalTrials.gov ID
- NCT04143412
- Acronym / sponsor ID
- RAAS blockers in albuminuria
- Keywords
- microalbuminuria, Diabetic nephropathy, Hperkalemia, Eplerenone, Ramipril
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Beni-Suef UniversityUniversity, hospital or other
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- Feb 2020 (estimated)
- Study completion
- Mar 2020 (estimated)
- First posted
- 29 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
- 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)
| Arm | Type | Receives |
|---|---|---|
| Tritace (Ramipril) | Active comparator | Drug: 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 |
| Eraloner (Eplerenone) | Active comparator | Drug: 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/Eraloner (Ramipril/Eplerenone)combination therapy | Active comparator | Drug: 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 |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tritace (Ramipril 10 mg)Also: Eraloner (Eplerenone 50 mg), Tritace/ Eraloner (Ramipril 10 mg/ Eplerenone 50 mg)Stratified randomized clinical trial | Drug | Eraloner (Eplerenone), Tritace (Ramipril), Tritace/Eraloner (Ramipril/Eplerenone)combination therapy |
Primary outcome
Urinary albumin/creatinin ratio (UACR)
Time frame: 24 weeks
Percentage change in albumin/creatinin ratio compared with the baseline value
3 secondary outcomes
Blood pressure
Time frame: 24 weeks
estimated Glomerular Filtration Rate (e GFR)
Time frame: 24 weeks
Serum K
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Background: PubMed 26239461Espinel E, Agraz I, Ibernon M, Ramos N, Fort J, Seron D. Renal Biopsy in Type 2 Diabetic Patients. J Clin Med. 2015 May 18;4(5):998-1009. doi: 10.3390/jcm4050998.
- Background: PubMed 19825147Zelmanovitz T, Gerchman F, Balthazar AP, Thomazelli FC, Matos JD, Canani LH. Diabetic nephropathy. Diabetol Metab Syndr. 2009 Sep 21;1(1):10. doi: 10.1186/1758-5996-1-10.
- Background: PubMed 24843491Cao Z, Cooper ME. Pathogenesis of diabetic nephropathy. J Diabetes Investig. 2011 Aug 2;2(4):243-7. doi: 10.1111/j.2040-1124.2011.00131.x.
- Background: PubMed 27536666Satirapoj B, Adler SG. Prevalence and Management of Diabetic Nephropathy in Western Countries. Kidney Dis (Basel). 2015 May;1(1):61-70. doi: 10.1159/000382028. Epub 2015 May 1.
- Background: PubMed 20535265Jalal S, Sofi FA, Abass SM, Alai MS, Bhat MA, Rather HA, Lone NA, Siddiqi MA. Effect of amlodipine and lisinopril on microalbuminuria in patients with essential hypertension: A prospective study. Indian J Nephrol. 2010 Jan;20(1):15-20. doi: 10.4103/0971-4065.62090.
- Background: PubMed 18580865Galle J. Reduction of proteinuria with angiotensin receptor blockers. Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S36-43. doi: 10.1038/ncpcardio0806.
- Background: PubMed 20730071Cagnoni F, Njwe CA, Zaninelli A, Ricci AR, Daffra D, D'Ospina A, Preti P, Destro M. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination. Vasc Health Risk Manag. 2010 Aug 9;6:549-59. doi: 10.2147/vhrm.s11816.
- Background: PubMed 29275368Cooper LB, Lippmann SJ, Greiner MA, Sharma A, Kelly JP, Fonarow GC, Yancy CW, Heidenreich PA, Hernandez AF. Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease. J Am Heart Assoc. 2017 Dec 23;6(12):e006540. doi: 10.1161/JAHA.117.006540.
- Individual participant dataSharing planned: No. To respect privacy and confidentiality of our patients
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mostafa O El Mokadem, M.D. principal investigator
Cardiology department,Faculty of Medicine, Beni-Suef University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tritace (Ramipril 10 mg) in people with Diabetic Nephropathy Type 2 and Microalbuminuria Due to Type 2 Diabetes Mellitus, run by Beni-Suef University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mostafa O El Mokadem, M.D. (+201009414408, mostafa.elmokadem9@med.bsu.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urinary albumin/creatinin ratio (UACR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04143412, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.