Apixaban vs Aspirin for Stroke Prevention in Atrial Fibrillation After Brain Bleed
(ASPIRE Trial)
Recruiting in Palo Alto (17 mi)
+142 other locations
Overseen byKevin N Sheth, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Yale University
Must not be taking: Anticoagulants, Antiplatelets
Disqualifiers: Active endocarditis, Hepatitis, Anemia, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
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.
12345Is 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.
13678How 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.
13679Eligibility 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.
+3 more
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.
+12 more
Trial 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
Participant Groups
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.
2Treatment groups
Active Control
Placebo Group
Group I: ApixabanActive Control1 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: AspirinPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Jackson Memorial HospitalMiami, FL
UVA Medical CenterCharlottesville, VA
University of California, IrvineOrange, CA
University of Minnesota Medical Center HospitalMinneapolis, MN
More Trial Locations
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)Collaborator
References
Apixaban: A Review in Venous Thromboembolism. [2020]Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is available for use in the treatment and secondary prevention of venous thromboembolism (VTE). Like other direct oral anticoagulants (DOACs), apixaban has generally predictable pharmacological properties and does not require routine anticoagulation monitoring. In large phase III trials, oral apixaban was noninferior to subcutaneous enoxaparin sodium overlapped with and followed by oral warfarin (enoxaparin/warfarin) in the treatment of adults with acute VTE over 6 months with regard to the incidence of recurrent VTE or VTE-related death (AMPLIFY), and was significantly more effective than placebo in the prevention of recurrent VTE or all-cause mortality over 12 months in patients who had completed 6-12 months' anticoagulation treatment for VTE (AMPLIFY-EXT). Apixaban was generally well tolerated in these trials; the risks of major bleeding and the composite endpoint of major or clinically relevant nonmajor (CRNM) bleeding with apixaban were significantly lower than enoxaparin/warfarin in AMPLIFY and not significantly different from that of placebo in AMPLIFY-EXT. Similarly, in Japanese adults with acute VTE (AMPLIFY-J), apixaban was associated with a significantly lower risk of major or CRNM bleeding than unfractionated heparin plus warfarin, and no cases of recurrent VTE or VTE-related death over 24 weeks. Thus, apixaban is useful therapeutic alternative for the management of adults with VTE.
Apixaban in the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. [2017]Conventional anticoagulant therapies can significantly reduce the risk of stroke and related complications in patients with atrial fibrillation (AF). Classic oral anticoagulants based on vitamin K antagonism have shown effectiveness in the prevention of thromboembolic complications in this clinical setting. Unfortunately, vitamin K antagonists that have shown effectiveness in the prevention of thromboembolic complications in patients with nonvalvular AF hold inherent limitations including delayed onset of action, narrow therapeutic index, variability of their response, need for repeated control and numerous interactions with food and other drugs. Since the frequency of stroke related to AF increases with age, guidelines from different scientific societies advise that the risk of bleeding for a patient should be quantified before exposure to anticoagulation and balanced against the risk of stroke with and without anticoagulation. A consequence of assessing this risk/benefit balance is that not all patients with AF at thromboembolic risk receive adequate anticoagulant treatment. Apixaban is a new oral anticoagulant with a direct, specific and reversible inhibitory action on coagulation factor Xa and with demonstrated safety and efficacy in the prophylaxis and treatment of venous thromboembolism in several clinical studies involving thousands of patients subjected to major orthopedic surgery. Results of two large phase III trials have demonstrated the efficacy and safety of apixaban compared with aspirin or warfarin, in the prevention of stroke in patients with AF. Apixaban demonstrated superiority over classic vitamin K antagonists on the previously specified outcomes of stroke, systemic embolism, major bleeding and death. For those patients unsuitable for treatment with vitamin K antagonists because of an excessive bleeding risk, apixaban showed more efficacy than aspirin in stroke prevention with a not statistically significant modest increase of major bleeding.
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]The impact of apixaban versus aspirin on ischemic stroke and major bleeding in relation to the CHADS(2) and CHA(2)DS(2)-VASc stroke risk scores in atrial fibrillation has not been investigated.
Safety and efficacy of apixaban in the treatment of atrial fibrillation. [2021]Atrial fibrillation is a common arrhythmia that increases the risk of stroke and systemic embolism. Warfarin is a highly effective treatment in reducing this risk, but a narrow therapeutic range, drug and food interactions, required monitoring, and bleeding limit its use. We review Apixaban, an oral inhibitor of Factor Xa, which has been shown in large randomized trials to have superior efficacy in stroke reduction without an excess in bleeding events when compared with aspirin in those deemed unsuitable to receive warfarin, and demonstrates superior efficacy in reducing stroke and systemic embolism in addition to a reduction in bleeding events when compared to warfarin.
Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. [2021]The direct factor Xa inhibitor apixaban (Eliquis(®)) has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring. This article reviews the efficacy and tolerability of oral apixaban to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial in patients with AF and at least one additional risk factor for stroke, apixaban recipients were significantly less likely than warfarin recipients to experience stroke or systemic embolism, major bleeding or death; the beneficial effects of treatment with apixaban versus warfarin were generally maintained across various patient subgroups. Apixaban recipients also had a significantly lower risk of intracranial haemorrhage than warfarin recipients. In the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients who have Failed or are Unsuitable for Vitamin K Antagonist Therapy) trial in patients with AF and at least one additional risk factor for stroke for whom vitamin K antagonist therapy was unsuitable, apixaban was associated with a significantly lower risk of stroke or systemic embolism than aspirin, without an increase in the risk of major bleeding. In conclusion, although longer-term efficacy and safety data are needed, apixaban is an important new option for use in patients with nonvalvular AF to reduce the risk of stroke or systemic embolism.
Apixaban: first global approval. [2021]Apixaban (Eliquis™), an oral direct factor Xa inhibitor, is being developed by Bristol-Myers Squibb and Pfizer as a therapy for the prevention and/or treatment of thrombotic disorders. Apixaban has been approved in the EU for the prevention of venous thromboembolism (VTE) after hip or knee replacement. A rolling submission for approval of apixaban for the prevention of stroke in patients with atrial fibrillation has also been initiated in the US. Worldwide phase III development of apixaban is underway for the prevention and treatment of VTE, and prevention of stroke in patients with atrial fibrillation. Development for acute coronary syndromes has been stopped following the discontinuation of the phase III APPRAISE-II trial. This article summarizes the milestones in the development of apixaban leading to this first approval for the prevention of VTE after hip or knee replacement.
Major bleeding with apixaban in atrial fibrillation: patient characteristics, management, and outcomes. [2018]To identify patient characteristics, bleed management, and bleed outcomes in patients experiencing an apixaban major bleeding event and to identify opportunities to improve the safe use of apixaban.
Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. [2021]Label="BACKGROUND">Apixaban (ELIQUIS®) is a direct oral anticoagulant authorised for multiple indications in the European Economic Area (EEA). Additional risk minimisation measures (aRMMs) to address the risk of bleeding include educational materials comprising a Prescriber Guide and Patient Alert Card.
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]Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy. This analysis explores patterns of bleeding and defines bleeding risks based on stroke risk with apixaban and aspirin.