Edoxaban for Atrial Fibrillation

(ENRICH-AF Trial)

Recruiting at 151 trial locations

Overseen By Amanda Taylor, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Population Health Research Institute

Must not be taking: NSAIDs

Disqualifiers: Recent intracranial hemorrhage, uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

948 Participants Needed

Trial Summary

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

The trial does not specify if you must stop all current medications. However, you cannot participate if you need ongoing oral anticoagulant therapy for conditions other than atrial fibrillation or if you need antiplatelet therapy where edoxaban isn't a suitable substitute. Chronic use of NSAIDs is also not allowed.

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 need ongoing oral anticoagulant or antiplatelet therapy for conditions other than atrial fibrillation. It's best to discuss your current medications with the trial team.

What data supports the idea that Edoxaban for Atrial Fibrillation is an effective drug?

The available research does not provide any data on Edoxaban for Atrial Fibrillation. The studies listed focus on treatments for breast cancer and uterine fibroids, not on Edoxaban or its effectiveness for Atrial Fibrillation. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Edoxaban for atrial fibrillation?

Research shows that Edoxaban is effective in preventing strokes and other blood clot-related events in patients with atrial fibrillation. It has been found to be as effective as warfarin, a commonly used blood thinner, but with a lower risk of major bleeding and death from heart-related causes. ^{6 7 8 9 10}

What safety data is available for Edoxaban in treating atrial fibrillation?

Edoxaban has been evaluated in several studies, including the ENGAGE AF-TIMI 48 trial, where it was found to be non-inferior to warfarin in preventing stroke and systemic embolic events in patients with nonvalvular atrial fibrillation. It showed a significantly lower rate of major bleeding, including intracranial hemorrhage, and cardiovascular death compared to warfarin. The Hokusai-VTE trial also demonstrated its safety in treating thromboembolic diseases. Real-world studies, such as those conducted in Germany and Turkey, continue to confirm its safety and effectiveness in routine clinical practice. ^{6 7 9 11 12}

Is Edoxaban safe for humans?

Edoxaban has been shown to be generally safe in humans, with studies indicating it causes fewer major bleeding events compared to warfarin, a commonly used blood thinner. It is well-tolerated and has a lower risk of causing serious bleeding in the brain and other fatal hemorrhages. ^{6 7 9 11 12}

Is the drug Edoxaban a promising treatment for Atrial Fibrillation?

Yes, Edoxaban is a promising drug for treating Atrial Fibrillation. It effectively prevents strokes and blood clots, has fewer bleeding risks compared to warfarin, and is easy to use with a once-daily pill that doesn't require regular blood tests. ^{6 7 13 14 15}

How is the drug Edoxaban unique for treating atrial fibrillation?

Edoxaban is unique because it is a direct factor Xa inhibitor that offers the convenience of once-daily oral dosing without the need for regular blood monitoring, unlike traditional treatments like warfarin. It also has fewer drug interactions and a lower risk of major bleeding, making it a safer option for many patients. ^{6 7 13 14 15}

What is the purpose of this trial?

This trial is testing if edoxaban, a daily blood-thinning medication, can safely reduce stroke risk in high-risk atrial fibrillation patients who have had previous brain bleeds. The goal is to see if it works better than not using any blood thinners or using simpler treatments. Edoxaban has been shown to be effective in preventing stroke with a lower risk of bleeding.

Research Team

Ashkan Shoamanesh, MD, FRCPC

Principal Investigator

Population Health Research Institute

Eligibility Criteria

This trial is for adults over 45 who've had a non-traumatic brain bleed, have atrial fibrillation with a CHA2DS2-VASc score of at least 2, and are stable. It's not for those with bleeding risks like ulcers, clotting disorders, liver disease, or sensitivity to edoxaban. Pregnant women and those unlikely to follow the study plan are also excluded.

Inclusion Criteria

I have been diagnosed with atrial fibrillation.

CHA2DS2-VASc score ≥2

Written informed consent provided

Exclusion Criteria

I have not had a brain bleed in the last 14 days.

My brain bleed isn't due to cancer, infection, or major blood vessel issues.

I am currently experiencing significant bleeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to receive either edoxaban 60/30 mg daily or non-anticoagulant medical therapy

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Edoxaban
• Non-anticoagulant medical therapy

Trial Overview The ENRICH-AF trial is testing if edoxaban (a blood thinner) is better than standard care without anticoagulants in preventing strokes in patients with atrial fibrillation who previously had a brain hemorrhage.

Participant Groups

Group I: Edoxaban 60/30mg daily Experimental Treatment 1 Intervention

Edoxaban 60/30 mg daily (lower dose depending on clinical criteria)

Group II: Non-anticoagulant medical therapy Active Control 1 Intervention

Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator)

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

Approved in United States as Savaysa for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Prevention of thromboembolism in atrial fibrillation

Approved in European Union as Lixiana for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism

Approved in Japan as Lixiana for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Findings from Research

Ribociclib combined with fulvestrant provides significant health benefits for patients with hormone receptor-positive and HER2-negative advanced breast cancer, resulting in an estimated gain of 0.96 quality-adjusted life-years (QALYs) compared to fulvestrant alone.

The cost-effectiveness analysis shows that ribociclib plus fulvestrant has an incremental cost-effectiveness ratio (ICER) of $157,343 per QALY gained, suggesting it is a potentially cost-effective treatment option for this patient population in Canada.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost Effectiveness of Ribociclib in Combination with Fulvestrant for the Treatment of Postmenopausal Women with HR+/HER2- Advanced Breast Cancer Who Have Received No or Only One Prior Line of Endocrine Therapy: A Canadian Healthcare Perspective. Stellato, D., Thabane, ME., Park, J., et al.[2021]

In a pilot study involving 18 postmenopausal women with advanced breast cancer, Formestane demonstrated a 25% objective response rate and 32% disease stabilization, indicating reasonable efficacy as a treatment option.

The treatment was well tolerated, with only 18% of patients experiencing mild and transient side effects, such as hot flushes and lethargy, and no patients needed to stop the medication due to toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of formestane in postmenopausal women with breast cancer. Joseph, JK., Lim, AK.[2015]

In a study involving 309 women with uterine fibroids, vilaprisan demonstrated significant efficacy in reducing heavy menstrual bleeding, with up to 60% of patients experiencing complete absence of bleeding at the highest dose compared to only 1.7% in the placebo group.

Vilaprisan was well tolerated with no safety concerns, and it led to reductions in fibroid volume of up to 41%, indicating its potential as an effective treatment option for managing symptoms associated with uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vilaprisan in women with uterine fibroids: the randomized phase 2b ASTEROID 1 study. Bradley, LD., Singh, SS., Simon, J., et al.[2019]

Fulvestrant (Faslodex) is now approved for treating advanced or metastatic breast cancer in postmenopausal women, and it is administered intramuscularly by healthcare professionals, typically resulting in minimal pain and infrequent injection-site reactions.

The manuscript includes case histories that illustrate the practical application of fulvestrant in clinical settings, emphasizing its role in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with fulvestrant ('Faslodex'): a nurse's perspective. Owers, R.[2018]

In a study of 409 postmenopausal women with advanced metastatic breast cancer, formestane showed comparable efficacy to tamoxifen, with 33% of patients responding to formestane and 37% to tamoxifen, indicating both treatments are effective options.

While both treatments had excellent tolerability, tamoxifen demonstrated a longer median duration of response (20 months) and better outcomes in terms of time to disease progression compared to formestane (15 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Pérez Carrión, R., Alberola Candel, V., Calabresi, F., et al.[2016]

In the ENGAGE AF-TIMI 48 trial involving patients with nonvalvular atrial fibrillation, edoxaban was found to be noninferior to warfarin in preventing strokes and systemic embolic events over a median treatment duration of 907 days.

Edoxaban demonstrated a significantly lower risk of major bleeding and cardiovascular-related deaths compared to warfarin, making it a safer and effective oral anticoagulant option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edoxaban: a review in nonvalvular atrial fibrillation. McCormack, PL.[2016]

In a study of 21,038 atrial fibrillation patients in Germany, edoxaban was found to be more effective than other oral anticoagulants, showing significantly lower risks of ischemic stroke or systemic embolism compared to apixaban, dabigatran, rivaroxaban, and vitamin K antagonists.

Edoxaban also exhibited a favorable safety profile, with lower risks of major bleeding compared to rivaroxaban and vitamin K antagonists, while showing similar bleeding risks to apixaban and dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study. Marston, XL., Wang, R., Yeh, YC., et al.[2022]

Edoxaban (Lixiana®) has been shown to be non-inferior to warfarin in treating deep venous thrombosis and pulmonary embolism, as well as in preventing systemic and cerebral embolisms in patients with non-valvular atrial fibrillation, based on results from the Hokusai-VTE and ENGAGE AF-TIMI 48 trials.

It demonstrated superior safety compared to warfarin, with a significantly lower incidence of major and clinically relevant bleeding episodes, including a notable reduction in cerebral and fatal hemorrhages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Edoxaban (LIXIANA®) : new oral anticoagulant forthetreatment and secondary prevention of thromboembolic disease]. Scheen, AJ., Lancellotti, P.[2019]

In a study involving 21,105 patients with atrial fibrillation followed for a median of 2.8 years, higher-dose edoxaban significantly reduced the risk of stroke or systemic embolic events in patients who had never used vitamin K antagonists (VKA), while showing similar efficacy to warfarin in those with prior VKA experience.

Both higher-dose and lower-dose edoxaban regimens were associated with a significant reduction in major bleeding risk compared to warfarin, regardless of whether patients had prior VKA exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†. O'Donoghue, ML., Ruff, CT., Giugliano, RP., et al.[2016]

The ETAF-TR study is a national, multicenter, prospective observational study in Turkey involving 858 patients, designed to evaluate the safety and effectiveness of edoxaban in real-life clinical practice for patients with atrial fibrillation over a 1-year follow-up period.

The primary focus of the study is to assess the occurrence of any overt bleeding events, which will help determine the safety profile of edoxaban and compare its effectiveness to previous trials like ENGAGE-AF and ETNA-AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Treatment Safety in Patients with Atrial Fibrillation on Edoxaban Therapy in Real-Life in Turkey Study: Design and Rationale. Önsel Türk, U., Alioğlu, E., Mavioğlu, Z., et al.[2022]

Edoxaban tosylate is being tested as an oral medication to prevent strokes and treat blood clots, with over 21,000 patients participating in the ENGAGE AF TIMI 48 trial comparing it to warfarin over 24 months.

In addition, the HOKUSAI VTE trial involves around 7,500 patients to evaluate edoxaban's effectiveness against warfarin for preventing recurrent blood clots, highlighting its potential as a safer alternative in thromboembolism management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edoxaban tosylate. [2016]

Edoxaban is an effective direct oral anticoagulant that reduces the risk of bleeding compared to warfarin while providing similar protection against thromboembolism, based on large phase III trials.

It is approved for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, with specific dosing considerations for patients with moderate renal impairment and those weighing ≤60 kg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct factor Xa inhibitor edoxaban: from bench to clinical practice. Brekelmans, M., Middeldorp, S., Coppens, M.[2016]

The ELIMINATE-AF trial, involving 632 patients undergoing atrial fibrillation ablation, found that uninterrupted edoxaban therapy resulted in significantly fewer major bleeding events (0.3%) compared to vitamin K antagonists (2.0%), suggesting it may be a safer option during this procedure.

While edoxaban showed a slightly higher rate of the primary endpoint (2.7% vs. 1.7% for VKAs), it still represents a viable alternative to VKAs for stroke prevention in patients undergoing AF ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial. Hohnloser, SH., Camm, J., Cappato, R., et al.[2020]

References

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

Cost Effectiveness of Ribociclib in Combination with Fulvestrant for the Treatment of Postmenopausal Women with HR+/HER2- Advanced Breast Cancer Who Have Received No or Only One Prior Line of Endocrine Therapy: A Canadian Healthcare Perspective. [2021]

2. Malaysia pubmed.ncbi.nlm.nih.gov

Pilot study of formestane in postmenopausal women with breast cancer. [2015]

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

Vilaprisan in women with uterine fibroids: the randomized phase 2b ASTEROID 1 study. [2019]

4. Scotland pubmed.ncbi.nlm.nih.gov

Clinical experience with fulvestrant ('Faslodex'): a nurse's perspective. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. [2016]

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

Edoxaban: a review in nonvalvular atrial fibrillation. [2016]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study. [2022]

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

Edoxaban, a Novel Oral Factor Xa Inhibitor. [2019]

9. Belgium pubmed.ncbi.nlm.nih.gov

[Edoxaban (LIXIANA®) : new oral anticoagulant forthetreatment and secondary prevention of thromboembolic disease]. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Edoxaban therapy increases treatment satisfaction and reduces utilization of healthcare resources: an analysis from the EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of atrial fibrillation (ENSURE-AF) study. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†. [2016]

12. Turkey pubmed.ncbi.nlm.nih.gov

Evaluation of Treatment Safety in Patients with Atrial Fibrillation on Edoxaban Therapy in Real-Life in Turkey Study: Design and Rationale. [2022]

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

Edoxaban tosylate. [2016]

14. England pubmed.ncbi.nlm.nih.gov

Direct factor Xa inhibitor edoxaban: from bench to clinical practice. [2016]

15. England pubmed.ncbi.nlm.nih.gov

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial. [2020]