Ramipril for Intermittent Claudication

Overseen By Neha K Woods, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Nebraska

Must not be taking: Ace inhibitors

Disqualifiers: Rest pain, Acute ischemic event, others

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if Ramipril can help patients with PAD who have severe leg pain walk better. Ramipril may improve muscle function by reducing damage and stiffness in the legs.

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 data supports the effectiveness of the drug ramipril for intermittent claudication?

Research shows that ramipril can more than double the maximum walking times in patients with peripheral artery disease and intermittent claudication, improving their walking ability and quality of life. ^{1 2 3 4 5}

Is ramipril generally safe for human use?

Ramipril is generally well tolerated in humans, with studies showing it is safe for treating high blood pressure and heart failure. It has a similar safety profile to other ACE inhibitors, with only about 5% of patients stopping treatment due to side effects. ^{1 3 4 6 7}

How does the drug ramipril differ from other treatments for intermittent claudication?

Ramipril is unique because it not only helps improve walking ability in patients with intermittent claudication, but it also reduces the risk of cardiovascular events like heart attacks and strokes, which is not a common benefit of other treatments for this condition. ^{1 3 4 5 8}

Research Team

Iraklis I Pipinos, MD

Principal Investigator

University of Nebraska

George P Casale, PhD

Principal Investigator

University of Nebraska

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Ramipril (ACE Inhibitor)

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.

Participant Groups

Group I: Ramipril Treatment Experimental Treatment 1 Intervention

6 months treatment with the medication Ramipril

Ramipril is already approved in Canada, India for the following indications:

Approved in Canada as Altace for:

• High blood pressure
• Heart failure
• Diabetic kidney disease

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Potential vascular mechanisms of ramipril induced increases in walking ability in patients with intermittent claudication. [2015]

2. England 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. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ramipril: a review of its use in preventing cardiovascular outcomes in high-risk patients. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on ramipril in the prevention of cardiovascular outcomes. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of ramipril on renal function in patients with intermittent claudication. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Comparison of ramipril and enalapril in patients with essential hypertension. [2013]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. [2018]

8. India pubmed.ncbi.nlm.nih.gov

Ramipril. [2013]