Ramipril for Intermittent Claudication

Overseen By Neha K Woods, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Nebraska

Must not be taking: Ace inhibitors

Disqualifiers: Rest pain, Acute ischemic event, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Ramipril, a medication, to determine if it can help people with peripheral artery disease (PAD) walk better and experience less leg pain. PAD often causes pain when walking, known as claudication, which eases with rest. The researchers believe Ramipril might improve muscle function in the legs by reducing damage and inflammation. Individuals who have experienced claudication for a while and find it difficult to exercise due to leg pain might be suitable for this trial. As a Phase 4 trial, Ramipril is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using ACE inhibitors or angiotensin II receptor blockers.

What is the safety track record for Ramipril?

Research has shown that ramipril is generally safe and well-tolerated. One study found that people with leg pain from narrowed arteries (intermittent claudication) who took ramipril for 24 weeks experienced significant improvements in walking ability and overall quality of life. Importantly, this study did not report any major side effects from ramipril use.

Additionally, the Heart Outcomes Prevention Study found that ramipril can reduce the risk of heart-related problems by 25% without causing major side effects, demonstrating its safety for long-term use in heart conditions. These findings suggest that ramipril is a safe option for people with peripheral artery disease. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for intermittent claudication, which typically include lifestyle changes, medications like cilostazol, or surgical procedures, Ramipril offers a different approach. Ramipril is an ACE inhibitor, which is traditionally used to manage high blood pressure and heart failure. Researchers are excited about its potential because it may improve blood flow and enhance walking ability by relaxing blood vessels, a novel application for this medication. If effective, Ramipril could provide a dual benefit of cardiovascular protection and symptom relief for those with intermittent claudication.

What is the effectiveness track record for Ramipril in treating intermittent claudication?

Research has shown that Ramipril, which participants in this trial will receive, can significantly aid individuals with intermittent claudication, a common issue in peripheral artery disease (PAD), in improving their walking ability. In studies, after 24 weeks of taking Ramipril, patients walked longer without pain and experienced an overall enhancement in their quality of life. These outcomes surpassed those achieved with some standard medications like cilostazol and pentoxifylline. Ramipril likely works by reducing muscle damage and improving muscle function in the legs. This medication has demonstrated promising results and offers hope for those facing walking difficulties due to PAD. ^{1 4 6 7 8}

Who Is on the Research Team?

Iraklis I Pipinos, MD

Principal Investigator

University of Nebraska

George P Casale, PhD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for individuals with Peripheral Artery Disease (PAD) who experience leg pain during walking due to claudication. They should have stable blood pressure, cholesterol, and diabetes management. Participants must not have severe kidney issues, a history of angioedema with ACE inhibitors, critical limb ischemia, or other conditions severely affecting their walking ability.

Inclusion Criteria

You have a history of long-term leg pain while walking.

Stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks

You have a history of leg pain that limits your ability to exercise, and this has been confirmed by a screening walking test administered by a vascular surgeon.

Exclusion Criteria

You have a history of severe blockage in the arteries leading to your kidneys on both sides.

You have experienced angioedema from taking ACE inhibitors before, or you are allergic to ramipril or other ACE inhibitors.

You have severe pain or tissue loss caused by peripheral artery disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 months of treatment with the medication Ramipril

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ramipril

Trial Overview The study tests if Ramipril can improve walking performance and quality of life in PAD patients by reducing muscle damage and fibrosis compared to standard treatments like cilostazol and pentoxifylline. It's hypothesized that Ramipril may help by decreasing oxidative damage in muscles.

How Is the Trial Designed?

Group I: Ramipril Treatment Experimental Treatment 1 Intervention

6 months treatment with the medication Ramipril

Ramipril is already approved in United States, Canada, European Union, India for the following indications:

Approved in United States as Altace for:

• High blood pressure
• Heart failure
• Diabetic kidney disease
• Prevention of heart attack, stroke, or cardiovascular death in high-risk patients

Approved in Canada as Altace for:

• High blood pressure
• Heart failure
• Diabetic kidney disease

Approved in European Union as Ramipril for:

• High blood pressure
• Heart failure
• Diabetic kidney disease
• Prevention of heart attack, stroke, or cardiovascular death in high-risk patients

Approved in India as Cardace for:

• High blood pressure
• Heart failure
• Diabetic kidney disease

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

In a study of 54 patients with intermittent claudication, ramipril was found to cause a temporary increase in serum creatinine and a decrease in glomerular filtration rate (GFR) at 5 weeks, but these changes were not clinically significant and returned to near baseline levels by 12 weeks.

The results suggest that ramipril can be safely prescribed to patients with intermittent claudication and normal renal function, as no patients experienced a significant rise in serum creatinine, indicating a low risk for renal complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ramipril on renal function in patients with intermittent claudication. Hobbs, SD., Claridge, MW., Wilmink, AB., et al.[2021]

Ramipril is an effective angiotensin-converting enzyme (ACE) inhibitor that helps lower blood pressure and is used to treat conditions like hypertension and heart failure.

The HOPE study demonstrated that ramipril can also prevent serious cardiovascular events, such as heart attacks, in individuals at high risk, highlighting its importance in cardiovascular health management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramipril. Smith, WH., Ball, SG.[2013]

In a randomized trial involving 159 patients with mild to moderate hypertension, ramipril demonstrated similar efficacy to enalapril in reducing blood pressure, with significant reductions in both supine and standing systolic blood pressures.

Ramipril achieved a greater overall decrease in plasma ACE activity (71%) compared to enalapril (48%), indicating that ramipril may provide stronger ACE inhibition, while both medications were well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of ramipril and enalapril in patients with essential hypertension. Ruddy, MC., Mroczek, WJ.[2013]

Ramipril is an effective treatment for mild to moderate hypertension, with about 85% of patients responding well to doses of 2.5 or 5 mg/day, and it shows similar efficacy to other ACE inhibitors and atenolol.

In patients with heart failure after a heart attack, ramipril significantly reduced the risk of all-cause mortality by 27%, demonstrating its potential benefits beyond just blood pressure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. Frampton, JE., Peters, DH.[2018]

In a study of 212 patients with peripheral artery disease, ramipril significantly improved walking distances, with an increase of 75 seconds in pain-free walking time and 255 seconds in maximum walking time compared to placebo over 6 months.

While ramipril led to modest blood pressure reductions and slight improvements in ankle-brachial index, the most common side effects were dizziness and persistent cough, which caused some patients to withdraw from the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication: a randomized controlled trial. Journal of the American Medical Association 2013; 309: 453-460. Kurklinsky, AK., Levy, M.[2018]

Ramipril is an effective ACE inhibitor that helps reduce the risk of serious cardiovascular events like heart attacks and strokes in patients aged 55 and older who are at high risk.

The medication is well tolerated and beneficial for various high-risk groups, including those with diabetes, peripheral arterial disease, or renal insufficiency, making it a key part of cardiovascular prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramipril: a review of its use in preventing cardiovascular outcomes in high-risk patients. Anderson, VR., Perry, CM., Robinson, DM.[2018]

In the HOPE study involving 9,297 patients over a mean duration of 4.5 years, ramipril significantly reduced the risk of major cardiovascular events (myocardial infarction, stroke, and cardiovascular death) by 22% compared to placebo.

Ramipril not only lowered the incidence of cardiovascular events but also reduced the progression of carotid artery wall thickness and complications related to diabetes, making it a crucial part of secondary prevention therapy for patients at increased cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on ramipril in the prevention of cardiovascular outcomes. Warner, GT., Perry, CM.[2018]

In a study of 165 patients with intermittent claudication, ramipril significantly increased levels of angiogenesis biomarkers (VEGF-A by 38% and FGF-2 by 64%) and reduced markers of thrombosis and inflammation, indicating its potential to improve blood flow and reduce clotting risks.

The changes in these biomarkers correlated with improved maximum walking times, suggesting that ramipril not only enhances circulation but also helps patients with peripheral artery disease walk longer distances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential vascular mechanisms of ramipril induced increases in walking ability in patients with intermittent claudication. Ahimastos, AA., Latouche, C., Natoli, AK., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23385271/

Effect of ramipril on walking times and quality of life among ... 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo.

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/1568251

Effect of Ramipril on Walking Times and Quality of Life ... Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24285767/

Angiotensin-converting enzyme inhibitors for intermittent ... ACE inhibitors may provide some relief of IC symptoms when used in patients with PAD. The greatest functional benefit has been seen with ramipril; ...

4. ahajournals.org ahajournals.org/doi/10.1161/circresaha.114.302420

Potential Vascular Mechanisms of Ramipril Induced ... We recently reported that ramipril more than doubled maximum walking times in patients with peripheral artery disease with intermittent claudication.

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT00681226

NCT00681226 | Angiotensin Converting Enzyme (ACE) ... Our preliminary findings indicate that the drug ramipril is much more effective in improving walking ability than current therapies. To be accepted as a new ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2496985/

Effect of ramipril on renal function in patients with ... The Heart Outcomes Prevention Study (HOPE) demonstrated that ramipril resulted in a blood-pressure-independent 25% reduction in cardiovascular events in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00681226

NCT00681226 | Angiotensin Converting Enzyme (ACE) ... This proposal extends our novel finding that the angiotensin-converting enzyme (ACE) inhibitor, ramipril markedly improves walking ability in patients with ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0021915013005984

Meta-analysis of angiotensin converting enzyme inhibitors ... This meta-analysis has shown that ACE inhibitors have the potential to improve walking ability in patients with intermittent claudication.