Apixaban vs Aspirin for Stroke Prevention in Atrial Fibrillation After Brain Bleed

(ASPIRE Trial)

Recruiting at 142 trial locations

Overseen By Neha Dangayach, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Yale University

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Active endocarditis, Hepatitis, Anemia, others

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: Unknown

Duration: 12-36 months

700 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary Aim: To determine if apixaban is superior to aspirin for prevention of the composite outcome of any stroke (hemorrhagic or ischemic) or death from any cause in patients with recent ICH and atrial fibrillation (AF). Secondary Aim: To determine if apixaban, compared with aspirin, results in better functional outcomes as measured by the modified Rankin Scale.

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 have a clear need for certain blood thinners or antiplatelet drugs like aspirin or clopidogrel.

What data supports the effectiveness of the drug Apixaban for stroke prevention in atrial fibrillation?

Research shows that Apixaban is more effective than aspirin in reducing the risk of stroke in patients with atrial fibrillation, without significantly increasing the risk of major bleeding. It has also been shown to be superior to warfarin in reducing stroke and systemic embolism, with a lower risk of bleeding. ^{1 2 3 4 5}

Is Apixaban safe for use in humans?

Apixaban (Eliquis) is generally well tolerated in humans, with studies showing a lower risk of major bleeding compared to some other treatments for blood clots. It is used for conditions like venous thromboembolism (VTE) and atrial fibrillation, and safety measures include educational materials to minimize bleeding risks. ^{1 3 6 7 8}

How does the drug apixaban differ from other treatments for preventing stroke in atrial fibrillation after a brain bleed?

Apixaban is unique because it is an oral medication that directly inhibits factor Xa, a key protein in the blood clotting process, and it does not require routine blood monitoring like some other anticoagulants. It offers a balance of reducing stroke risk with a comparable bleeding risk to aspirin, making it a suitable option for patients who cannot use traditional blood thinners like warfarin. ^{1 3 6 7 9}

Research Team

Kevin N Sheth, MD

Principal Investigator

Yale University

Hooman Kamel, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults who've had a recent brain bleed (ICH) and atrial fibrillation but no ICH in the past year, no severe kidney or liver issues, not pregnant/breastfeeding, and without certain blood conditions. They must be able to start the trial within 14-180 days after their ICH.

Inclusion Criteria

I have a type of irregular heartbeat not caused by a heart valve issue.

Provision of signed and dated informed consent form by patient or legally authorized representative

You have had bleeding inside your brain confirmed by a brain CT or MRI.

Exclusion Criteria

Concomitant participation in a competing trial

I have had or will have a procedure to close off a part of my heart.

I have an ongoing heart infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either apixaban or aspirin for stroke prevention and recovery

12-36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Apixaban
• Aspirin

Trial Overview The study aims to see if apixaban is better than aspirin at preventing strokes or death in people with atrial fibrillation who recently had an ICH. It also looks at whether apixaban leads to better recovery outcomes using a disability scale.

Participant Groups

Group I: Apixaban Active Control 1 Intervention

Apixaban dosing will be 5 mg tablet in morning and 5 mg tablet in evening. A reduced dose of 2.5 mg tablet in morning and 2.5 mg tablet in evening will be used if: (1) ≥2 of the following are present: age ≥80 years, body weight ≤60 kg, or serum creatinine 1.5-2.4 mg/dL, or (2) Patient is taking a strong CYP3A4/pGP inhibitor (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin).

Group II: Aspirin Placebo Group 1 Intervention

Aspirin dose will be 81 mg tablet once daily.

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

Approved in European Union as Eliquis for:

• Deep vein thrombosis
• Pulmonary embolism
• Nonvalvular atrial fibrillation

Approved in United States as Eliquis for:

• Deep vein thrombosis
• Pulmonary embolism
• Nonvalvular atrial fibrillation
• Stroke prevention

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

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]

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]

In patients with atrial fibrillation, apixaban was found to be more effective than aspirin in preventing ischemic strokes, particularly benefiting those in high-risk groups as determined by the CHADS(2) and CHA(2)DS(2)-VASc scores.

Both apixaban and aspirin showed similar rates of major bleeding, indicating that apixaban provides a safer option for stroke prevention without increasing bleeding risk compared to aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modification of outcomes with aspirin or apixaban in relation to CHADS(2) and CHA(2)DS(2)-VASc scores in patients with atrial fibrillation: a secondary analysis of the AVERROES study. Lip, GY., Connolly, S., Yusuf, S., et al.[2013]

Apixaban is an oral Factor Xa inhibitor that has been shown to effectively reduce the risk of stroke and systemic embolism in patients with atrial fibrillation, outperforming aspirin in those who cannot take warfarin.

In large randomized trials, Apixaban not only demonstrated superior efficacy in stroke reduction compared to warfarin but also resulted in fewer bleeding events, making it a safer alternative for patients at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of apixaban in the treatment of atrial fibrillation. Martin, A., Stewart, R.[2021]

In the ARISTOTLE trial, apixaban significantly reduced the risk of stroke, systemic embolism, major bleeding, and death compared to warfarin in patients with nonvalvular atrial fibrillation, showing consistent benefits across various patient subgroups.

The AVERROES trial demonstrated that apixaban was more effective than aspirin in preventing stroke or systemic embolism in patients unsuitable for vitamin K antagonist therapy, without increasing the risk of major bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Keating, GM.[2021]

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]

In a study of 49 elderly patients (average age 79) who experienced major bleeding while on apixaban, 94% had a history of hypertension and 68% were using antiplatelet therapy, indicating a high risk profile for bleeding events.

Despite the majority of patients receiving packed red blood cell transfusions for management, there were concerns about the appropriateness of concurrent antiplatelet therapy, as 64.7% of those on aspirin had no clear indication for its use, highlighting opportunities to improve the safe use of apixaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major bleeding with apixaban in atrial fibrillation: patient characteristics, management, and outcomes. Eisho, S., Salem, NM., Hoffman, JL., et al.[2018]

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]

In the AVERROES trial involving 5599 patients with atrial fibrillation, apixaban was associated with a slightly higher annual bleeding rate (4.5%) compared to aspirin (3.8%), but this difference was not statistically significant, indicating comparable safety profiles.

Both apixaban and aspirin showed similar patterns of bleeding risks, with higher CHADS2 scores correlating with increased rates of both bleeding and stroke, but apixaban provided a reduced relative risk of stroke compared to aspirin, suggesting a favorable risk-benefit balance for apixaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bleeding during treatment with aspirin versus apixaban in patients with atrial fibrillation unsuitable for warfarin: the apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment (AVERROES) trial. Flaker, GC., Eikelboom, JW., Shestakovska, O., et al.[2022]

References

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

Apixaban: A Review in Venous Thromboembolism. [2020]

2. Spain pubmed.ncbi.nlm.nih.gov

Apixaban in the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. [2017]

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

Modification of outcomes with aspirin or apixaban in relation to CHADS(2) and CHA(2)DS(2)-VASc scores in patients with atrial fibrillation: a secondary analysis of the AVERROES study. [2013]

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

Safety and efficacy of apixaban in the treatment of atrial fibrillation. [2021]

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

Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. [2021]

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

Apixaban: first global approval. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Major bleeding with apixaban in atrial fibrillation: patient characteristics, management, and outcomes. [2018]

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

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. [2021]

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

Bleeding during treatment with aspirin versus apixaban in patients with atrial fibrillation unsuitable for warfarin: the apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment (AVERROES) trial. [2022]