Ticagrelor and HPR Screening for Peripheral Arterial Disease

Overseen By Kyle Markel

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kyle Markel

Must not be taking: Prasugrel, Ticlopidine, Anticoagulants

Disqualifiers: Emergency treatment, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

31 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, specifically prasugrel, ticlopidine, and any oral anticoagulation medications, before participating.

What data supports the effectiveness of the drug Ticagrelor for Peripheral Arterial Disease?

Research shows that Ticagrelor, an antiplatelet drug, is effective in reducing cardiovascular events in patients with peripheral arterial disease, similar to its benefits in heart-related conditions. Antiplatelet therapy, like Ticagrelor, helps prevent blood clots, which is crucial for managing peripheral arterial disease. ^{1 2 3 4 5}

Is ticagrelor generally safe for humans?

Ticagrelor is generally well-tolerated, but it can cause slow heart rhythms and fainting in some people. It also has a warning for bleeding risks, which is common for drugs that prevent blood clots. ^{1 5 6 7 8}

How is the drug Ticagrelor unique for treating peripheral arterial disease?

Ticagrelor is unique because it is a reversible, direct inhibitor of the ADP P2Y12 receptor, which is different from other antiplatelet drugs like clopidogrel that are irreversible. This makes Ticagrelor potentially more effective in patients with high platelet reactivity who do not respond well to other treatments. ^{1 4 5 7 9}

What is the purpose of this trial?

This is a randomized controlled trial designed to evaluate the role of screening for and intervening on patients with high on treatment platelet reactivity undergoing lower extremity arterial endovascular interventions.

Eligibility Criteria

This trial is for individuals with peripheral arterial disease who are scheduled for angioplasty or stenting of the superficial femoral artery or popliteal artery. It's not open to those on oral anticoagulants, pregnant women, patients with prior surgical interventions at the same site, or those unable to tolerate antiplatelet drugs.

Inclusion Criteria

I am scheduled for a procedure to open arteries in my leg.

I have peripheral arterial disease.

Exclusion Criteria

My surgery is not on the superficial femoral or popliteal artery.

You have received treatment in an emergency situation.

I am currently taking blood thinner pills.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo femoropopliteal angioplasty or stenting and are either screened and treated for HPR or receive guideline-based therapy without HPR screening

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for primary patency, amputation, and major adverse cardiovascular events

1 year

Quarterly visits (in-person)

Treatment Details

Interventions

• Point of care screening for HPR
• Ticagrelor 90mg

Trial Overview The study tests if screening and treating high platelet reactivity (HPR) with Ticagrelor can benefit patients undergoing lower extremity arterial endovascular procedures. Participants will be randomly assigned to receive either HPR screening followed by treatment or no screening.

Participant Groups

Group I: Experimental: screening/treating for HPR Experimental Treatment 2 Interventions

Participants randomized to this arm will be screened and treated for HPR. Pharmacogenetics testing for CYP2C19 polymorphisms will be collected, stored, and analyzed at study completion.

Group II: Control: guideline based therapy Active Control 1 Intervention

Participants randomized to this arm will receive usual care without screening for HPR. Pharmacogenetics testing for CYP2C19 polymorphisms will be collected, stored, and analyzed at study completion.

Ticagrelor 90mg is already approved in United States, European Union for the following indications:

Approved in United States as Brilinta for:

• Acute coronary syndrome
• History of myocardial infarction
• Coronary artery disease
• Ischemic stroke
• Transient ischemic attack

Approved in European Union as Brilinta for:

• Acute coronary syndromes
• Myocardial infarction
• Unstable angina
• Coronary artery disease

Who Is Running the Clinical Trial?

Kyle Markel

Lead Sponsor

Trials

1

Recruited

30+

Marissa Jarosinski

Lead Sponsor

Trials

1

Recruited

30+

Rohan Kulkarni

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

In a study of 37 patients with critical limb ischemia (CLI) and high on-clopidogrel platelet reactivity, ticagrelor was found to be safe and effective, achieving significant platelet inhibition without any major bleeding events during a follow-up of 11.3 months.

The use of ticagrelor resulted in a high primary efficacy outcome rate of 92% for cardiovascular death and major amputation, indicating its potential as a beneficial treatment in complex limb-salvage procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with ticagrelor in patients with critical limb ischemia and high on-clopidogrel platelet reactivity undergoing complex peripheral endovascular procedures. Spiliopoulos, S., Katsanos, K., Pastromas, G., et al.[2022]

Antiplatelet drugs, such as ticlopidine and aspirin, significantly reduce the risk of serious vascular events in patients with peripheral arterial disease, showing similar benefits as seen in cardiovascular diseases, based on a meta-analysis of 28 trials.

Long-term use of ticlopidine has been confirmed to lower mortality and reduce complications related to cardiovascular health, while also helping to prevent graft occlusion after arterial surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic antiplatelet therapy in peripheral arterial disease. Verhaeghe, R.[2022]

Patients with peripheral arterial disease face a significantly higher risk of cardiovascular events, including stroke and heart attack, and are six times more likely to die from cardiovascular causes compared to those without the disease.

Combining antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors can lead to an estimated 80% reduction in relative risk for cardiovascular issues, highlighting the importance of multi-drug therapy alongside lifestyle changes and possible revascularization to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular risk prevention in peripheral artery disease. Hackam, DG.[2013]

In a post-hoc analysis of the PLATO trial involving 18,624 patients, ticagrelor showed a 16% reduction in cardiovascular death, myocardial infarction, and stroke compared to clopidogrel, indicating its potential efficacy in patients with peripheral artery disease (PAD) and acute coronary syndromes (ACS).

The rates of major bleeding were similar between ticagrelor (14.8%) and clopidogrel (17.9%), suggesting that ticagrelor can be used without a significant increase in bleeding risk, which is important for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: Data from the PLATO Trial. Patel, MR., Becker, RC., Wojdyla, DM., et al.[2018]

Ticagrelor is an effective oral antiplatelet medication commonly used in patients with acute coronary syndrome and after procedures like PCI, acting as a reversible inhibitor of the P2Y12 receptor.

Despite its efficacy, Ticagrelor can cause bradyarrhythmias and ventricular pauses, as demonstrated in a case study of a 58-year-old man who experienced syncope after loading with the drug, highlighting the need for monitoring its cardiac effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor-Induced Syncope/Bradyarrhythmia. Kotaru, V., Kalavakunta, JK.[2021]

Ticagrelor (Brilinta™) was approved by the FDA for treating acute coronary syndromes based on the PLATO trial, which involved 18,624 patients and compared its efficacy to clopidogrel over 6-12 months.

Despite its approval, there were significant concerns from FDA reviewers regarding its efficacy and safety, particularly related to bleeding risks and the potential reduction in effectiveness when used with high doses of aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. Serebruany, VL.[2018]

Ticagrelor is an effective antiplatelet medication used in patients with acute coronary syndrome, helping to reduce the risk of heart attacks and other cardiovascular events.

Clinical studies have shown that ticagrelor provides a greater reduction in major adverse cardiovascular events compared to traditional treatments like clopidogrel, making it a preferred choice in acute settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. Fuller, R., Chavez, B.[2021]

Ticagrelor has been shown to be more effective than clopidogrel in treating patients with acute coronary syndromes and superior to placebo for patients in the chronic phase after a myocardial infarction, based on randomized studies.

Patients with both myocardial infarction and peripheral artery disease (PAD) may experience greater benefits from ticagrelor, but more research is needed to confirm its efficacy and safety in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease. Nicolau, JC., Baracioli, LM., Giugliano, RP.[2018]

Ticagrelor is a new type of P2Y(12) antagonist that works differently from traditional antiplatelet medications like clopidogrel and prasugrel, providing a potentially more effective option for treating acute coronary syndromes.

Clinical trials have shown that ticagrelor, when used with aspirin, has a favorable safety profile and can overcome some limitations associated with clopidogrel, making it a valuable addition to antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. Wijeyeratne, YD., Joshi, R., Heptinstall, S.[2022]

References

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

Initial experience with ticagrelor in patients with critical limb ischemia and high on-clopidogrel platelet reactivity undergoing complex peripheral endovascular procedures. [2022]

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

Prophylactic antiplatelet therapy in peripheral arterial disease. [2022]

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

Cardiovascular risk prevention in peripheral artery disease. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: Data from the PLATO Trial. [2018]

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

Ticagrelor-Induced Syncope/Bradyarrhythmia. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. [2018]

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

Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. [2022]