Anti-Coagulant + Anti-Platelet Therapy for Stroke Prevention

(CAPTIVA Trial)

Recruiting at 101 trial locations

Overseen By Jesse Thon

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: University of Florida

Must not be taking: Thrombolytics, Antithrombotics, CYP3A4 inhibitors

Disqualifiers: Intracranial tumor, Cardiac embolism, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

1683 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates whether two experimental treatments can better prevent strokes and other vascular problems compared to a standard treatment. It uses different combinations of medicines: clopidogrel (an anti-platelet drug), rivaroxaban (an anti-coagulant), and ticagrelor (an anti-platelet drug), alongside aspirin. Individuals who have recently experienced a stroke and have significant artery narrowing might be suitable for this trial. Participants must be able to take pills and meet other health-related criteria. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking stroke prevention treatments.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it does mention that you cannot take any antithrombotic medication other than aspirin, unless it's for specific conditions like DVT prevention. It's best to discuss your current medications with the trial team.

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

Research shows that taking ticagrelor with aspirin can greatly reduce the risk of stroke, but it also increases the chance of bleeding. One study found that the risk of major bleeding with ticagrelor is similar to that with aspirin alone. Another study showed that using ticagrelor by itself reduced adverse events by 27%.

For rivaroxaban with aspirin, studies indicate it is more effective at reducing strokes than aspirin alone, but there is still a risk of major bleeding. In one study, about 1.8% of patients experienced major bleeding with rivaroxaban. Overall, both treatments have been researched and show promise in reducing strokes, but they come with bleeding risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring new approaches to stroke prevention. Ticagrelor, in combination with aspirin, offers a dual-antiplatelet strategy that may enhance blood flow better than standard options like clopidogrel. Rivaroxaban, paired with aspirin, provides an anticoagulant approach that directly inhibits factor Xa, potentially reducing the risk of stroke more effectively than traditional treatments. These combinations aim to offer improved protection against strokes by utilizing different mechanisms than the current standard of care.

What evidence suggests that this trial's treatments could be effective for stroke prevention?

In this trial, participants will join different treatment arms to evaluate stroke prevention. Research has shown that taking ticagrelor with aspirin, one of the experimental arms, can lower the risk of an ischemic stroke by 20% compared to other treatments. When used alone, ticagrelor reduced the chance of having a stroke by 11% and proved more effective than clopidogrel in preventing ischemic strokes.

Another experimental arm involves rivaroxaban with aspirin. Studies, including the COMPASS trial, consistently showed this combination effectively prevents strokes, significantly reducing them compared to using aspirin alone. These findings suggest that both ticagrelor and rivaroxaban, when used with aspirin, could be strong options for preventing strokes in this trial. ^{1 2 4 6 7}

Who Is on the Research Team?

Brian L. Hoh, MD, MBA

Principal Investigator

University of Florida

Marc I. Chimowitz, MBChB

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

Adults aged 30-80 with recent symptoms or signs of a stroke due to 70-99% blockage in a major brain artery, who can swallow pills and have certain heart or blood vessel conditions. Excluded are those with previous stent treatments for the lesion, bleeding disorders, severe liver issues, uncontrolled high blood pressure, substance abuse, certain heart conditions that could cause clots, planned major surgeries within 90 days after joining the trial, severe neurological deficits preventing independence, life expectancy under one year due to other illnesses.

Inclusion Criteria

I have been treating my diabetes with insulin for 15 years or more.

I have a narrowed artery due to plaque buildup confirmed by imaging tests.

Index infarct is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery) documented by CTA, MRA, or catheter angiography

Exclusion Criteria

Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study, or currently breastfeeding

I haven't had major surgery in the last 30 days and don't plan any in the next 90 days.

I have a heart condition that could cause blood clots.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ticagrelor, rivaroxaban, or clopidogrel in combination with aspirin to prevent stroke and vascular death

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on ischemic stroke, intracerebral hemorrhage, or vascular death

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Clopidogrel
• Rivaroxaban
• Ticagrelor

Trial Overview The study is testing if adding rivaroxaban or ticagrelor (or both) to aspirin is better than just clopidogrel plus aspirin at reducing the risk of another stroke or death from vascular causes within a year. Participants will be randomly assigned to one of these treatment combinations.

How Is the Trial Designed?

Group I: Experimental Arm: Ticagrelor and Aspirin Experimental Treatment 2 Interventions

Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily)

Group II: Experimental Arm: Rivaroxaban and Aspirin Experimental Treatment 2 Interventions

Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)

Group III: Standard of Care Arm: Clopidogrel and Aspirin Active Control 2 Interventions

Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily)

Clopidogrel is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Approved in United States as Plavix for:

• Reduction of myocardial infarction and stroke in patients with acute coronary syndrome
• Reduction of myocardial infarction and stroke in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease

Approved in Canada as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Approved in Japan as Plavix for:

• Prevention of recurrence of ischemic cerebrovascular disorder
• Prevention of recurrence of myocardial infarction

Approved in China as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

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, a potent oral platelet inhibitor, significantly reduces the risk of death, myocardial infarction, or stroke in patients with acute coronary syndromes compared to clopidogrel, as shown in the PLATO study.

While ticagrelor does not increase the overall rate of major bleeding compared to clopidogrel, it is associated with a higher incidence of non-procedure-related bleeding, indicating a need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month. Ticagrelor (Brilique): potent oral antagonist of platelet activity]. Lancellotti, P.[2018]

The COMPASS study showed that combining rivaroxaban with acetylsalicylic acid (ASA) significantly reduces the risk of stroke, cardiovascular death, and myocardial infarction by 24% compared to ASA alone, highlighting the efficacy of dual-pathway thrombosis inhibition in patients with atherosclerotic diseases.

Patients receiving the combination therapy experienced a 67% reduction in the risk of recurrent stroke, with an annual incidence of only 1.1% compared to 3.4% in those on ASA alone, indicating a strong safety profile and effectiveness in preventing recurrent noncardioembolic ischemic strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current opportunities for secondary prevention of atherothrombotic stroke]. Maksimova, MY.[2021]

The combination of antiplatelet and anticoagulant drugs in patients with acute coronary syndromes poses significant challenges due to a lack of strong clinical evidence and guidelines, especially as many patients also require double antiplatelet therapy.

The ATLAS-ACS 2 TIMI 51 study showed promising results for the use of rivaroxaban in combination with double antiplatelet therapy, suggesting potential benefits for patients with acute coronary syndromes, although the overall evidence remains limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anticoagulants and dual antiplatelet therapy combined, a challenge to our intelligence]. Morais, J.[2015]

Aspirin remains the first-line antiplatelet drug for long-term prevention of recurrent heart issues after a myocardial infarction, while dual antiplatelet therapy has been shown to improve outcomes in acute coronary syndromes despite a higher risk of bleeding.

The article reviews the best combinations of aspirin with P2Y12 inhibitors (like clopidogrel, prasugrel, or ticagrelor) and discusses new antithrombotic agents that may enhance treatment effectiveness in high-risk patients, particularly those with both atrial fibrillation and acute coronary syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet and antithrombotic treatment for secondary prevention in ischaemic heart disease. Lettino, M., Leonardi, S., De Maria, E., et al.[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]

Ticagrelor (Brilinta) has been approved by the FDA as an oral antiplatelet medication to be used with low-dose aspirin for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS).

Ticagrelor will compete with existing medications like clopidogrel (Plavix) and prasugrel (Effient), especially as clopidogrel is expected to become available as a generic option soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? [2018]

Antiplatelet treatment is essential for preventing atherothrombotic strokes, but traditional drugs like aspirin and thienopyridines have limitations, including increased bleeding risk and variable patient response.

Newer antiplatelet agents, such as ticagrelor and prasugrel, do not significantly improve stroke prevention compared to aspirin or clopidogrel and also carry a higher risk of bleeding, highlighting the need for new drug targets in antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stroke prevention: from available antiplatelet drugs to novel molecular targets. Di Minno, MN., Momi, S., Di Minno, A., et al.[2019]

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]

Aspirin and clopidogrel are established antiplatelet agents that are effective and safe for patients with a history of stroke or transient ischemic attack, highlighting their importance in managing cerebrovascular atherothrombosis.

Novel antiplatelet agents like prasugrel, ticagrelor, and vorapaxar show limited efficacy in preventing cerebrovascular events and may pose risks for patients with a history of stroke, indicating the need for careful consideration in their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy versus safety: the dilemma of using novel platelet inhibitors for the treatment of patients with ischemic stroke and coronary artery disease. Iannopollo, G., Camporotondo, R., De Ferrari, GM., et al.[2021]

In a study involving 29 healthy volunteers, the generic drug Ticaloguard® was found to have similar therapeutic effects and safety profiles compared to the brand-name drug Brilique® in terms of platelet aggregation, indicating that it can be used interchangeably in treating acute coronary syndrome.

The study emphasizes the importance of testing the therapeutic equivalence of generic drugs, especially for critical medications, rather than relying solely on bioequivalence, to ensure patient safety and effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial. Zarif, B., Soliman, L., Sabry, NA., et al.[2022]

Dual antiplatelet therapy, consisting of aspirin and clopidogrel, is essential for preventing ischemic events in patients with coronary atherosclerotic disease, especially during acute coronary syndromes and after stent placement.

While triple antithrombotic therapy (dual antiplatelet therapy plus warfarin) can effectively prevent thromboembolism and stent thrombosis, it significantly increases the risk of bleeding, highlighting the need for careful management and expertise in balancing these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining antiplatelet and anticoagulant therapies. Holmes, DR., Kereiakes, DJ., Kleiman, NS., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10944328/

Assessing the Safety and Efficacy of Rivaroxaban for Stroke ... The results of the systematic revealed a total of 19/21 (84%) studies advocating the effectiveness of rivaroxaban for stroke prevention.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1802686

Rivaroxaban for Stroke Prevention after Embolic ... The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group ( ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.035864

Stroke Outcomes in the COMPASS Trial | Circulation Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31578012/

Real-World Outcomes of Rivaroxaban Treatment in ... Safety and effectiveness event rates were higher in patients with prior ischemic stroke/TIA than those without. This might be explained by differences in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0914508719300036

Real-world outcomes of the Xarelto Post-Authorization ... Real-world outcomes of the XAPASS showed incidence rates of major bleeding and thromboembolic events, suggesting that rivaroxaban is safe and effective in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38496142/

Assessing the Safety and Efficacy of Rivaroxaban for ... The results for rivaroxaban against warfarin showed an improved safety index and effectiveness of rivaroxaban. The total effect size for the ...

7. tandfonline.com tandfonline.com/doi/full/10.1080/14740338.2023.2181334

Safety and effectiveness of rivaroxaban for prevention of ... Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and ...