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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Ticagrelor to determine its effectiveness for people with peripheral arterial disease, a condition that reduces blood flow in the legs, who are undergoing procedures to open blocked arteries. One group will receive screening and treatment based on their body's response to medication, while the other group will receive standard care without additional screening. This study targets individuals planning for angioplasty or stenting in specific leg arteries, provided they have not undergone previous surgery or emergency treatment in those areas. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Ticagrelor is generally well-tolerated, but some safety concerns exist. One study found that while it reduced major heart-related events in patients with type 2 diabetes, it also increased the risk of bleeding. Another study showed that patients taking Ticagrelor had a higher chance of bleeding compared to those taking clopidogrel, a similar drug.

Screening for high on-treatment platelet reactivity (HPR) can identify patients who do not respond well to antiplatelet drugs. This is important because patients with HPR face a higher risk of heart problems.

Overall, Ticagrelor has been used successfully for other conditions, but it carries some risks, mainly related to bleeding. Patients should be aware of these risks when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ticagrelor for peripheral arterial disease because it takes a different approach by focusing on high platelet reactivity (HPR). While most treatments for this condition rely on standard antiplatelet therapies like aspirin or clopidogrel, ticagrelor is a direct-acting P2Y12 receptor inhibitor. This specificity allows it to more effectively prevent blood clots in patients with genetic variations affecting typical treatment responses. Additionally, the trial involves pharmacogenetic screening, which could personalize therapy and enhance its effectiveness by tailoring the treatment to individual genetic profiles.

What evidence suggests that this trial's treatments could be effective for peripheral arterial disease?

Research has shown that using ticagrelor with aspirin can help reduce blood flow problems in the limbs, particularly for individuals with peripheral artery disease (PAD) and diabetes. One study found that this combination led to fewer procedures needed to improve blood flow. However, ticagrelor did not prove more effective than clopidogrel, another blood thinner, in reducing heart-related issues in PAD patients.

In this trial, participants in the experimental arm will undergo point-of-care screening for high platelet reactivity (HPR) to assess the effectiveness of blood thinners like ticagrelor. This is crucial because some individuals with PAD may not respond well to certain medications, and testing can help identify these cases. Participants in the control arm will receive usual care without HPR screening. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4691818/

Current status of high on-treatment platelet reactivity in ... It is a very practical, rapid and well-standardized point-of-care test that measures platelet-induced aggregation to fibrinogen-coated beads in whole blood in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0741521423024278

Platelet function testing and clinical outcomes in peripheral ... PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization.

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/17085381231214324

High on-treatment platelet reactivity in peripheral arterial ... HTPR during clopidogrel treatment ranges from 9.8 to 77%, and during aspirin treatment ranges from 4.1 to 50% of PAD patients.

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.116.004904

Platelet Reactivity and Clinical Outcomes After Coronary ... Patients with peripheral arterial disease (PAD) have high rates of adverse cardiovascular events after percutaneous coronary intervention ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35381075/

Platelet reactivity testing in peripheral artery disease This article aims to provide a review of the literature surrounding platelet functional testing in patients with PAD receiving oral P2Y12 inhibitors.