Diabetes Type 2Phase 4NCT01743014
Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy
A Phase 4 study testing Ramipril and Clopidogrel in people with Diabetes Type 2 and Diabetic Nephropathy, run by AHEPA University Hospital at 2 sites in Greece.
Trial summary
The purpose of this study is to determine whether the combination with ramipril and clopidogrel leads to further improvement of endothelial function, reduction of oxidative stress and reduction of vascular inflammation, compared with ramipril monotherapy, in patients with Diabetes Mellitus type 2 and diabetic… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetes Type 2, Diabetic Nephropathy, Vascular Disease
- What is being tested?
- Ramipril and Clopidogrel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesGreece
- Study dates
- Jul 2012to Jul 2015
- Phase
- Phase 4
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- patients with diabetic nephropathy and estimated GFR <30ml/min with Modification of Diet in Renal Disease equation (MDRD equation)
- baseline potassium > 5.2 meq/L
- patients with nephrotic proteinuria defined as albumine to creatinine ratio (ACR)> 3.5 g/g or as proteinuria >3.5 g per 1.73 m2 per 24 hours
- history or evidence of non-diabetic kidney disease
- history of stroke, peripheral artery disease, coronary artery disease
- history or evidence of a secondary form of hypertension
Show all 16Show fewer
- history of severe hepatic failure, malignancy, severe endocrinopathy,autoimmune disease or chronic inflammatory disease
- any known bleeding or platelet disorder or platelets <100.000/μL
- heart failure in New York Heart Association(NYHA) functional class II-IV
- inability or unwillingness on the part of the patient to sign the Patient Consent Form
- known hypersensitivity to ramipril or to clopidogrel
- Women of child-bearing potential
- use of oral anticoagulants or other antithrombotic treatment
- use of glitazones
- patients receiving statins should be on a stable dose of at least 3 months prior to study initiation and dose should be constant during the study
- any surgical or medical condition which in the opinion of the investigator may expose the patient to a higher risk in participation in the study
Trial locations and contacts
2 sites in 1 country.
Greece2 sites, 2 recruiting
- Recruiting
AHEPA University Hospital
Thessaloniki, Thessaloniki, 546 36
Fotios S Iliadis, Lecturer of Internal Medicine, +302310993587, iliadis@med.auth.gr
Vaia F Bougatsa, Resident of Internal Medicine, +306944334265, vaiabou@yahoo.gr
- Recruiting
Aristotle University of Thessaloniki/ AHEPA University Hospital
Thessaloniki, Thessaloniki
Vaia F Bougatsa, MD
About this study
Official title: A Prospective, Randomized, Two Period, With an Intermediate Wash Out Period, Cross-over Study to Compare the Effects of Either Combined Therapy With Ramipril and Clopidogrel or Ramipril Monotherapy on Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Patients With Type 2 Diabetes and Diabetic Nephropathy
The purpose of this study is to determine whether the combination with ramipril and clopidogrel leads to further improvement of endothelial function, reduction of oxidative stress and reduction of vascular inflammation, compared with ramipril monotherapy, in patients with Diabetes Mellitus type 2 and diabetic nephropathy.
Read the detailed description
- Cardiovascular disease is the leading cause of deaths in diabetic population with diabetic nephropathy.
- Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an angiotensin-converting-enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB)
- Diabetic patients at increased cardiovascular risk should receive an antiplatelet agent for primary prevention.
Methods:
An open label,randomized, two period cross-over design study, involving patients with type 2 diabetes and diabetic nephropathy. After a 4 weeks wash out period for ACE inhibitors or Angiotensin receptor blockers (week 0, baseline) 60 patients will be randomized to receive ramipril(10 mg) only or ramipril (10 mg) and clopidogrel (75mg) for 12 weeks exchanging their treatment for a further 12 weeks, after a 2 week wash out period for clopidogrel. Patients will be examined and measurements will be taken at baseline (week 0), and at the end of 12, 14, and 26 weeks.
- Conditions
- Diabetes Type 2, Diabetic Nephropathy, Vascular Disease
- Being tested
- Ramipril, Clopidogrel
- Keywords
- diabetes, diabetic nephropathy, vascular inflammation, oxidative stress, endothelial dysfunction, Asymmetric dimethylarginine, High sensitivity CRP, albumine to creatinine ratio, isoprostane, clopidogrel, ramipril, carotid intima media thickness
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Nephropathies, Vascular Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamiprilDrug
Also called Triatec
Patients will receive 10 mg ramipril throughout the study. Each dose will be taken orally once daily. The duration of treatment with ramipril is 26 weeks
ClopidogrelDrug
Also called Plavix, Iscover
12 weeks treatment with ramipril 10 mg and clopidogrel 75 mg once daily followed by a 2 week wash out period for clopidogrel and subsequently additional 12 weeks treatment wit both drugs after cross over.
| Study group | Role | What they receive |
|---|---|---|
| ramipril | Active comparator | Ramipril 10 mg tablets. Each dose will be taken orally with water once daily. Receives: Drug: Ramipril |
| clopidogrel and ramipril | Active comparator | clopidogrel 75mg tablet and ramipril 10mg. Each drug will be taken orally with water once daily Receives: Drug: Ramipril; Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in ADMA as biomarker of endothelial dysfunction.
Measured: Baseline to week 12 and week 14 to week 26
Changes in High-sensitivity C-reactive protein (HsCRP) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in hsCRP as biomarker of vascular inflammation
Measured: Baseline to week 12 and week 14 to week 26
Changes in soluble CD40 Ligand (sCD40L)blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in soluble CD40 Ligand as biomarker of vascular inflammation.
Measured: Baseline to week 12 and week 14 to week 26
Changes in urine 8-isoprostane-F2 levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in urine 8-isoprostane-F2 as biomarker of oxidative stress.
Measured: Baseline to week 12 and week 14 to week 26
Reduction in albumine to creatine ratio after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in albumine to creatine ratio as an index of cardiovascular disease
Measured: Baseline to week 12 and week 14 to week 26
Secondary outcomes (3)
Changes in ADMA blood levels after treatment with ramipril
Evaluation of the effect of ramipril, as antihypertensive therapy, in endothelial dysfunction in patients with diabetes mellitus type 2 and diabetic nephropathy
Measured: baseline to week 26
Increase of Glomerular Filtration Rate (GFR) after combined treatment with ramipril and clopidogrel and after ramipril monotherapy
Measured: baseline to week 12 and week 14 to week 26
Change from baseline in carotid intima-media thickness after combined therapy with ramipril and clopidogrel and after ramipril monotherapy
Measured: baselibe to week 12 and week 14 to week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2014 (estimated)
- Study completionJul 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Type 2Studies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AHEPA University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Aristotle University Of Thessaloniki
- Responsible party
- Principal investigator, Vaia Bougatsa, AHEPA University Hospital
- Investigators
- Fotios S Iliadis, Lecturer of Internal Medicine, Study director, AHEPA University Hospital/ Aristotle University of ThessalonikiVaia F Bougatsa, Resident of Internal Medicine, Principal investigator, AHEPA University Hospital/ Aristotle University of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01743014
- Sponsor's protocol ID
- 15/10-7-2012
- Status last verified
- Nov 2012
- First submitted
- 21 Nov 2012
- Last updated
- 6 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
PubMed 35224730
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Two Period, With an Intermediate Wash Out Period, Cross-over Study to Compare the Effects of Either Combined Therapy With Ramipril and Clopidogrel or Ramipril Monotherapy on Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Patients With Type 2 Diabetes and Diabetic Nephropathy
- ClinicalTrials.gov ID
- NCT01743014
- Acronym / sponsor ID
- 15/10-7-2012
- Conditions
- Diabetes Type 2, Diabetic Nephropathy, Vascular Disease
- Keywords
- diabetes, diabetic nephropathy, vascular inflammation, oxidative stress, endothelial dysfunction, Asymmetric dimethylarginine, High sensitivity CRP, albumine to creatinine ratio
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- AHEPA University HospitalUniversity, hospital or other
- Collaborators
- Aristotle University Of Thessaloniki
- Study start
- Jul 2012
- Primary completion
- Jul 2014 (estimated)
- Study completion
- Jul 2015 (estimated)
- First posted
- 6 Dec 2012 (estimated)
- 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 purpose of this study is to determine whether the combination with ramipril and clopidogrel leads to further improvement of endothelial function, reduction of oxidative stress and reduction of vascular inflammation, compared with ramipril monotherapy, in patients with Diabetes Mellitus type 2 and diabetic nephropathy.
Detailed description
- Cardiovascular disease is the leading cause of deaths in diabetic population with diabetic nephropathy.
- Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an angiotensin-converting-enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB)
- Diabetic patients at increased cardiovascular risk should receive an antiplatelet agent for primary prevention.
Methods:
An open label,randomized, two period cross-over design study, involving patients with type 2 diabetes and diabetic nephropathy. After a 4 weeks wash out period for ACE inhibitors or Angiotensin receptor blockers (week 0, baseline) 60 patients will be randomized to receive ramipril(10 mg) only or ramipril (10 mg) and clopidogrel (75mg) for 12 weeks exchanging their treatment for a further 12 weeks, after a 2 week wash out period for clopidogrel. Patients will be examined and measurements will be taken at baseline (week 0), and at the end of 12, 14, and 26 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ramipril | Active comparator | Drug: RamiprilRamipril 10 mg tablets. Each dose will be taken orally with water once daily. |
| clopidogrel and ramipril | Active comparator | Drug: Ramipril, Drug: Clopidogrelclopidogrel 75mg tablet and ramipril 10mg. Each drug will be taken orally with water once daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- patients with diabetic nephropathy and estimated GFR <30ml/min with Modification of Diet in Renal Disease equation (MDRD equation)
- baseline potassium > 5.2 meq/L
- patients with nephrotic proteinuria defined as albumine to creatinine ratio (ACR)> 3.5 g/g or as proteinuria >3.5 g per 1.73 m2 per 24 hours
- history or evidence of non-diabetic kidney disease
- history of stroke, peripheral artery disease, coronary artery disease
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 |
|---|---|---|
| RamiprilAlso: TriatecPatients will receive 10 mg ramipril throughout the study. Each dose will be taken orally once daily. The duration of treatment with ramipril is 26 weeks | Drug | clopidogrel and ramipril, ramipril |
| ClopidogrelAlso: Plavix, Iscover12 weeks treatment with ramipril 10 mg and clopidogrel 75 mg once daily followed by a 2 week wash out period for clopidogrel and subsequently additional 12 weeks treatment wit both drugs after cross over. | Drug | clopidogrel and ramipril |
Primary outcome
Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Time frame: Baseline to week 12 and week 14 to week 26
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in ADMA as biomarker of endothelial dysfunction.
Changes in High-sensitivity C-reactive protein (HsCRP) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Time frame: Baseline to week 12 and week 14 to week 26
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in hsCRP as biomarker of vascular inflammation
Changes in soluble CD40 Ligand (sCD40L)blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Time frame: Baseline to week 12 and week 14 to week 26
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in soluble CD40 Ligand as biomarker of vascular inflammation.
Changes in urine 8-isoprostane-F2 levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Time frame: Baseline to week 12 and week 14 to week 26
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in urine 8-isoprostane-F2 as biomarker of oxidative stress.
Reduction in albumine to creatine ratio after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy
Time frame: Baseline to week 12 and week 14 to week 26
The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in albumine to creatine ratio as an index of cardiovascular disease
3 secondary outcomes
Changes in ADMA blood levels after treatment with ramipril
Time frame: baseline to week 26
Increase of Glomerular Filtration Rate (GFR) after combined treatment with ramipril and clopidogrel and after ramipril monotherapy
Time frame: baseline to week 12 and week 14 to week 26
Change from baseline in carotid intima-media thickness after combined therapy with ramipril and clopidogrel and after ramipril monotherapy
Time frame: baselibe to week 12 and week 14 to week 26
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2012.
- Derived from this study: PubMed 35224730Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
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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.
Fotios S Iliadis, Lecturer of Internal Medicine study director
AHEPA University Hospital/ Aristotle University of Thessaloniki
Vaia F Bougatsa, Resident of Internal Medicine principal investigator
AHEPA University Hospital/ Aristotle University of Thessaloniki
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ramipril and Clopidogrel in people with Diabetes Type 2 and Diabetic Nephropathy, run by AHEPA University Hospital at 2 sites in Greece.
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 0 inclusion and 16 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 6 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Fotios S Iliadis, Lecturer of Internal Medicine (+306974960728, iliadis@med.auth.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy (time frame: Baseline to week 12 and week 14 to week 26). The study lists 5 primary outcomes in all. 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 NCT01743014, which also lists 1 linked publication.
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 6 Dec 2012.