Anticoagulation + Antiplatelet Therapy for Post-Operative Atrial Fibrillation

(PACES Trial)

Recruiting at 105 trial locations

Overseen By Ellen Moquete, RN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Dual antiplatelets

Disqualifiers: Permanent AF, Cardiogenic shock, Liver cirrhosis, 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: 270

Duration: 90 days

3200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of adding oral anticoagulants (blood thinners) to antiplatelet therapy (medications to prevent blood clots) for preventing blood clots after heart surgery. It targets individuals who develop new or recurring atrial fibrillation (irregular heartbeat) within a week after coronary artery bypass graft surgery. Those experiencing this irregular heartbeat for more than an hour or on multiple occasions after surgery may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on dual antiplatelet therapy (DAPT) or have a pre-existing need for long-term oral anticoagulation, you may not be eligible to participate.

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

Research has shown that blood thinners like Apixaban (brand name Eliquis) are generally safe. Studies have found that Apixaban outperforms warfarin for individuals with non-valvular atrial fibrillation, a type of irregular heartbeat. This indicates its effectiveness and ease of use for patients. Many studies involving thousands of participants have tested Apixaban's safety. Although it can increase the risk of bleeding, this is a known side effect of blood thinners. Overall, Apixaban maintains a strong safety record when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining anticoagulation and antiplatelet therapy for post-operative atrial fibrillation because it offers a potentially more effective way to prevent blood clots compared to using either treatment alone. While standard options often involve using just an anticoagulant or an antiplatelet agent, this approach aims to leverage the strengths of both. The oral anticoagulant in this study provides a comprehensive clot prevention strategy, possibly reducing the risk of stroke and other complications following surgery. This combination could lead to improved patient outcomes with potentially fewer side effects than higher doses of a single agent.

What evidence suggests that this trial's treatments could be effective for post-operative atrial fibrillation?

Research has shown that oral anticoagulants (OACs), or blood-thinning medications taken by mouth, can reduce the risk of stroke and serious brain issues in people with irregular heartbeats after heart surgery. One study found that newer blood thinners, known as direct oral anticoagulants (DOACs), caused fewer bleeding problems than warfarin, a commonly used blood thinner. In this trial, participants may receive Apixaban, a type of OAC, which demonstrated a much lower risk of causing major bleeding compared to other similar drugs. Another group in this trial will receive an antiplatelet-only strategy, such as aspirin. In people with irregular heartbeats, Apixaban also reduced the risk of stroke or blood clots traveling through the body more effectively than aspirin. These findings suggest that using OACs could benefit those with irregular heartbeats after heart bypass surgery. ^{5 6 7 8 9}

Who Is on the Research Team?

Annetine C Gelijns, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Marc Gillinov, MD

Principal Investigator

The Cleveland Clinic

John Alexander, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults (≥18 years) who develop new, persistent or recurrent atrial fibrillation within 7 days after having a coronary artery bypass graft surgery. It's not for those with valve surgeries, major complications like stroke or bleeding post-surgery, pregnant women, people unable to consent or follow the study plan, those with less than one year life expectancy due to other diseases, prior history of atrial fibrillation, indications for long-term anticoagulation therapy outside of this condition, severe liver disease or recent participation in another drug/device trial.

Inclusion Criteria

I am 18 or older and had bypass surgery for heart disease.

My heart rhythm issue lasted over an hour or happened again within a week after my bypass surgery.

Exclusion Criteria

I am having a procedure to repair my heart valve at the same time as my bypass surgery.

I haven't used any experimental drugs or devices in the last 30 days.

My doctor expects I have less than a year to live due to my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an OAC-based strategy or an antiplatelet-only strategy for 90 days

90 days

Study follow-up visits at 90 days, phone follow-up at 30, 60, and 180 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of thromboembolic and bleeding events

180 days

Phone follow-up at 180 days

Registry and Digital Health Substudy

Participants who decline randomization are enrolled in a registry; up to 500 participants may use a wearable heart rhythm monitor for 30 days post-discharge

30 days for digital health substudy

What Are the Treatments Tested in This Trial?

Interventions

• Antiplatelet-only strategy
• Oral Anticoagulant

Trial Overview

The study tests if adding oral anticoagulants to standard antiplatelet therapy is more effective and safe in preventing blood clots and reducing major bleeding risks in patients who have developed atrial fibrillation after coronary artery bypass surgery. Participants are either given just antiplatelets or a combination of antiplatelets and oral anticoagulants.

How Is the Trial Designed?

Group I: Antiplatelet Therapy Active Control 1 Intervention

Antiplatelet-only strategy

Group II: Oral Anticoagulant Active Control 1 Intervention

OAC-based strategy

Oral Anticoagulant is already approved in European Union, United States for the following indications:

Approved in European Union as Eliquis for:

• Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• Prevention of deep vein thrombosis and pulmonary embolism following hip or knee replacement surgery

Approved in United States as Eliquis for:

• Reduction in the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• Prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, in patients who have undergone hip or knee replacement surgery
• Treatment of deep vein thrombosis and pulmonary embolism

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Apixaban, an oral direct factor Xa inhibitor, has been approved in the EU for preventing venous thromboembolism (VTE) after hip or knee replacement surgeries, demonstrating its efficacy in reducing the risk of blood clots in these patients.

The drug is also undergoing phase III trials for preventing strokes in patients with atrial fibrillation, indicating its potential for broader applications in thrombotic disorders, although development for acute coronary syndromes has been halted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. Watson, J., Whiteside, G., Perry, C.[2021]

Apixaban is an effective oral anticoagulant for treating and preventing venous thromboembolism (VTE), showing noninferiority to the traditional enoxaparin/warfarin treatment in large phase III trials over 6 months.

It has a lower risk of major bleeding compared to enoxaparin/warfarin and is well tolerated, making it a safer alternative for patients with VTE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: A Review in Venous Thromboembolism. Greig, SL., Garnock-Jones, KP.[2020]

A reliable and sensitive method was developed to measure apixaban and its major metabolite in human plasma, which is crucial for clinical testing and monitoring of this anticoagulant drug.

The method showed excellent precision and accuracy, with low limits of quantification, making it effective for supporting clinical studies involving apixaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LC-MS/MS determination of apixaban (BMS-562247) and its major metabolite in human plasma: an application of polarity switching and monolithic HPLC column. Pursley, J., Shen, JX., Schuster, A., et al.[2022]

Apixaban is an effective oral medication for preventing venous thromboembolism (VTE) after knee or hip replacement surgery, showing better efficacy than subcutaneous enoxaparin sodium in phase III trials ADVANCE-2 and -3 without significantly increasing bleeding risk.

While apixaban did not meet noninferiority criteria compared to a specific enoxaparin regimen in the ADVANCE-1 trial, it was associated with fewer bleeding complications, suggesting it may be a safer option for thromboprophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: a review of its use in the prevention of venous thromboembolism after knee or hip replacement surgery. Deeks, ED.[2021]

Oral anticoagulant therapy, including both vitamin K antagonists and novel oral anticoagulants, is essential for preventing thromboembolic events in patients with atrial fibrillation, with a positive net clinical benefit in nearly all cases due to the balance of thrombosis prevention and bleeding risk.

The review highlights the complexities of managing anticoagulant therapy in various clinical situations, such as urgent surgeries or acute strokes, emphasizing the need for clear guidelines on when to modify or resume anticoagulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticoagulation management in nonvalvular atrial fibrillation: current and future directions. Kornej, J., Potpara, T., Lip, GY.[2019]

Healthcare professionals (HCPs) and patients demonstrated satisfactory knowledge of bleeding risks associated with apixaban, with 96.1% of HCPs recognizing symptoms that require immediate attention and 71.2% of patients identifying abnormal bleeding as a significant side effect.

The study found that a significant majority of HCPs (97.8%) who received the Prescriber Guide utilized it in patient discussions, and 90.9% of patients who received the Patient Alert Card read it at least once, indicating effective distribution and utilization of these educational materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. Mayall, S., Kahlon, R., Al-Dakkak, I., et al.[2021]

Apixaban is a new oral anticoagulant that directly inhibits factor Xa, showing superior efficacy and safety in preventing strokes in patients with atrial fibrillation compared to traditional vitamin K antagonists like warfarin.

In large phase III trials, apixaban not only reduced the risk of stroke and systemic embolism but also had a favorable safety profile, making it a better option for patients at high risk of bleeding who cannot use vitamin K antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban in the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Pujadas-Mestres, L., Escolar, G., Arellano-Rodrigo, E., et al.[2017]

Citations

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sciencedirect.com

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Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52–0.65, I2 = 90%), dabigatran (RR ...

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nejm.org

nejm.org/doi/full/10.1056/NEJMoa2310234

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An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is ...

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seeeliquisevidence.com/clinical-outcomes

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An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7584711/

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ELIQUIS U.S. Prescribing Information

The safety of ELIQUIS has been evaluated in 1 Phase II and 3 Phase III studies including 5924 patients exposed to ELIQUIS 2.5 mg twice daily undergoing major ...