Asundexian for Stroke Prevention

(OCEANIC-STROKE Trial)

No longer recruiting at 1387 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bayer

Must be taking: Antiplatelets

Must not be taking: Anticoagulants

Disqualifiers: Atrial fibrillation, Mechanical valve, 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

Compensation: Varies

Number of Visits: 3

Duration: 3 to 31 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called asundexian (BAY2433334) to determine if it can better prevent strokes in individuals who recently experienced a non-cardioembolic ischemic stroke or a high-risk mini-stroke (TIA). These strokes occur when a blood clot blocks blood flow to the brain. Participants will receive either asundexian or a placebo (a pill with no active ingredients) alongside their usual treatment to assess whether asundexian reduces the risk of future strokes without increasing bleeding problems. Ideal participants are those who had a stroke due to a clot outside the heart within the last 72 hours and are already receiving standard care. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking stroke prevention treatment.

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. However, it mentions that participants will receive asundexian or placebo in addition to standard antiplatelet therapy, suggesting you may continue your current antiplatelet medications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it mentions that participants will receive the study treatment in addition to standard antiplatelet therapy, so you may continue taking antiplatelet medications.

Is there any evidence suggesting that asundexian is likely to be safe for humans?

Research has shown that asundexian, a new blood thinner, has been tested for safety in people at risk of strokes. In one study, about 8-10% of participants taking asundexian experienced significant safety issues like bleeding, similar to the placebo group. This suggests that asundexian does not increase the risk of bleeding more than a non-active treatment.

Another study compared asundexian to apixaban, another blood thinner, in people with atrial fibrillation (a heart condition with irregular heartbeats). The study found that asundexian had a similar safety level, meaning it did not cause more bleeding than apixaban. This is important because bleeding is a major concern with blood thinners.

Overall, the studies suggest that asundexian is generally well-tolerated, with a similar risk of side effects as other treatments or placebos. However, like any treatment, some risk remains, and discussing possible side effects with the study team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke prevention?

Unlike the standard blood thinners used for stroke prevention, such as warfarin or direct oral anticoagulants like apixaban, Asundexian stands out because it specifically targets Factor XIa in the blood clotting process. This different mechanism of action aims to reduce the risk of strokes without significantly increasing the risk of bleeding, which is a common side effect of current treatments. Researchers are excited about Asundexian's potential to offer a safer alternative for patients who are at high risk for bleeding complications with existing therapies.

What evidence suggests that asundexian might be an effective treatment for preventing ischemic strokes?

In this trial, participants will receive either asundexian or a placebo. Research has shown that asundexian, a new blood thinner, aims to prevent strokes by targeting a specific part of the blood clotting process. Studies suggest that asundexian might prevent strokes with a lower risk of bleeding than other blood thinners. However, the PACIFIC-Stroke trial did not find a significant reduction in strokes compared to a placebo. Current evidence indicates that while asundexian shows promise for stroke prevention, its effectiveness compared to existing treatments remains under study. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults who've recently had a non-cardioembolic ischemic stroke or high-risk TIA/mini-stroke and are receiving standard antiplatelet therapy. It's not for those with strokes from rare causes, atrial fibrillation/flutter, heart-related blood clots, or mechanical valves needing anticoagulation.

Inclusion Criteria

I recently had a stroke that wasn't caused by a heart issue.

I have had a stroke or have artery problems in my brain or body.

Exclusion Criteria

I have a heart condition that requires blood thinners.

I had a stroke caused by a blood clot less than a week ago.

My stroke was caused by a procedure or a rare condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either asundexian or placebo once a day in addition to standard antiplatelet therapy

3 to 31 months

Approximately every 3 months, alternating between phone calls and in-person visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 visits after treatment period

What Are the Treatments Tested in This Trial?

Interventions

• Asundexian (BAY2433334)
• Placebo

Trial Overview The study tests if Asundexian, a new anticoagulant tablet taken daily for 3 to 31 months alongside standard therapy, is more effective than a placebo at preventing further ischemic strokes without increasing bleeding risks.

How Is the Trial Designed?

Group I: Asundexian Experimental Treatment 1 Intervention

Participants will receive asundexian.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo.

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

In a study involving 372 asymptomatic patients with carotid stenosis, aspirin did not significantly reduce the risk of ischemic events compared to a placebo over a median follow-up of 2.3 years.

The annual rate of ischemic events was similar between the aspirin group (11.0%) and the placebo group (12.3%), indicating that aspirin does not provide a long-term protective effect in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group. Côté, R., Battista, RN., Abrahamowicz, M., et al.[2021]

The Prostate Cancer Prevention Trial demonstrated that finasteride reduced the prevalence of prostate cancer by 25% over 7 years in men over 55, indicating its potential as a chemopreventive agent.

While finasteride showed a reduction in overall prostate cancer rates, there was an increase in higher-grade cancers, suggesting the need for careful consideration of trial design biases and the clinical significance of the cancers prevented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should finasteride be used to prevent prostate cancer? Fleshner, N., Kulkarni, G.[2022]

In a study involving 5028 patients with acute ischemic stroke, NXY-059 did not show any significant benefit in reducing disability compared to placebo, with similar outcomes on the modified Rankin scale after 90 days.

NXY-059 also failed to reduce the incidence of intracranial hemorrhages associated with the use of alteplase, indicating it is ineffective for treating acute ischemic stroke within 6 hours of symptom onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II Trials. Diener, HC., Lees, KR., Lyden, P., et al.[2016]

No neuroprotective drug has proven effective for treating acute ischaemic stroke in clinical settings, despite success in animal studies, highlighting a significant gap in translating research to human treatment.

Following newly established guidelines for drug development, such as thorough dose-response evaluations and functional testing, may improve the chances of success for compounds like NXY-059, which is currently in clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why do neuroprotective drugs that are so promising in animals fail in the clinic? An industry perspective. Green, AR.[2019]

In a study of 101 patients with benign prostatic hyperplasia (BPH), a 16-week placebo treatment resulted in a significant 24% decrease in symptom scores and a 14% increase in peak flow rate, highlighting the substantial impact of placebo effects in BPH management.

The maximal placebo effect, which can lead to about a 40% reduction in symptoms, typically occurs within the first four to six months, suggesting that the timing of treatment initiation is crucial for evaluating the efficacy of new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia. The ALFECH Study Group. Hansen, BJ., Meyhoff, HH., Nordling, J., et al.[2019]

Dutasteride significantly improves urinary symptoms and reduces prostate volume in men with benign prostatic hyperplasia (BPH), outperforming placebo in clinical trials involving nine studies with men aged 40 and over.

While dutasteride is effective, it is associated with a higher rate of drug-related adverse events; however, combining it with tamsulosin leads to even greater symptom relief compared to tamsulosin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dutasteride for the treatment of symptomatic benign prostatic hyperplasia (BPH): a systematic review and meta-analysis. Park, T., Choi, JY.[2022]

In a study of 205 patients with Benign Prostatic Hyperplasia (BPH) over 12 weeks, alfuzosin significantly reduced symptoms and improved urinary flow compared to placebo.

Alfuzosin was found to be safe, with no significant differences in adverse events or withdrawals between the alfuzosin and placebo groups, indicating it has a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alfuzosin in the treatment of benign prostatic hyperplasia: effects on symptom scores, urinary flow rates and residual volume. A multicentre, double-blind, placebo-controlled trial. ALFECH Study Group. Hansen, BJ., Nordling, J., Mensink, HJ., et al.[2013]

In a randomized, double-blind clinical trial involving 125 patients with referred shoulder pain, applying a force to the C5 vertebra using a mechanically assisted instrument (MAI) significantly improved internal rotation strength after 6 months (P = 0.04).

While the treatment cohort experienced a reduction in the frequency of extreme shoulder pain (from weekly to monthly), there was no significant change in the severity of pain or other functional outcomes compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Applying a Force to C5 by a Mechanically Assisted Instrument on Referred Pain to the Shoulder. Hardas, GM., Murrell, GAC.[2021]

Aspirin is effective for the treatment and prevention of ischemic stroke, but the required dosage varies based on the specific indication, with higher doses (160-325 mg) needed for acute ischemic stroke and atrial fibrillation (325 mg).

Low-dose aspirin (50-81 mg daily) may not be sufficient for some patients at risk of ischemic stroke, highlighting the need for individualized dosing based on clinical guidelines and patient conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin dosing for the prevention and treatment of ischemic stroke: an indication-specific review of the literature. Ansara, AJ., Nisly, SA., Arif, SA., et al.[2013]

In a study of 19 patients with mild to moderate essential hypertension and intermittent claudication, once-daily doxazosin significantly reduced both systolic and diastolic blood pressure after 14 weeks, with mean blood pressures decreasing from 170/100 mm Hg to 161/93 mm Hg.

Doxazosin was effective in normalizing blood pressure in 75% of patients and improved the severity of hypertension in 81.3% of patients, with only mild side effects reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter study of doxazosin in the treatment of patients with mild or moderate essential hypertension and concomitant intermittent claudication. Catalano, M., Libretti, A.[2019]

Current guidelines recommend oral anticoagulants for patients with cardioembolic strokes and antiplatelet agents, like aspirin, for those with ischemic strokes due to atherothrombosis, highlighting the importance of tailored long-term treatment.

Meta-analyses suggest that the effectiveness of aspirin in preventing vascular events is consistent across various doses, leading to a recommendation for lower doses (50-325 mg daily) due to their better safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet therapy: new foundations for optimal treatment decisions. Albers, GW., Tijssen, JG.[2007]

In a study involving 24 rabbits undergoing spine fusion, daily subcutaneous injections of abaloparatide resulted in a 100% fusion rate compared to only 45% in the control group, indicating its strong efficacy in promoting spinal fusion.

Radiographic analysis showed that abaloparatide significantly increased bone formation and quality, with higher bone volume and improved trabecular structure, suggesting it enhances the biological processes necessary for successful spinal fusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abaloparatide Enhances Fusion and Bone Formation in a Rabbit Spinal Arthrodesis Model. Morse, KW., Moore, H., Kumagai, H., et al.[2023]

The use of an ESP block during minimally invasive spinal surgery significantly reduced opioid consumption by 37.7% in the first 48 hours post-surgery, indicating its efficacy in pain management.

Patients receiving the ESP block reported lower pain levels (measured by VAS) and improved short-term outcomes (PROST scores) compared to the placebo group, although there were no significant differences in blood loss or wound healing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Erector Spinae Plane Block Decrease Analgesia Requirements After Minimal-Invasive Posterior Transpedicular Stabilization in Patients With Vertebral Body Fracture? A Prospective, Randomized, Double-Blind Controlled Study. Holas, M., Hlásny, J., Gajdoš, R., et al.[2023]

In a study involving 100 patients undergoing lumbar spine fusion surgeries, batroxobin and its combination with tranexamic acid significantly reduced both intraoperative and postoperative blood loss compared to a placebo.

The mean intraoperative blood loss was lowest in the batroxobin group (268.32 mL) and the combination group (256.96 mL), indicating their effectiveness, while no significant differences were found in blood transfusion needs or complications like deep vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery. Nagabhushan, RM., Shetty, AP., Dumpa, SR., et al.[2021]

In a clinical trial with 73 participants suffering from rotator cuff related shoulder pain, omega-3 polyunsaturated fatty acids (PUFAs) showed a modest improvement in pain and disability outcomes, particularly noted in the Shoulder Pain and Disability Index (SPADI) at 3 months.

However, there was no significant difference in the primary outcome, the Oxford Shoulder Score (OSS), between the omega-3 group and the placebo group at the 2-month mark, indicating that while there may be some benefits, they are not robust.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled trial of long-chain omega-3 polyunsaturated fatty acids in the management of rotator cuff related shoulder pain. Sandford, FM., Sanders, TA., Wilson, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12314250/

Evaluating the Safety and Efficacy of Asundexian in ... Outcomes included all-cause mortality, cardiovascular death, ischemic stroke, stroke or systemic embolism, major/clinically relevant non-major ...

2. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2407105

Asundexian versus Apixaban in Patients with Atrial ... Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.

3. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.043198

Effect of the Factor XIa Inhibitor Asundexian According to ... These exploratory, unconfirmed results suggest that asundexian may prevent new embolic infarcts but not small artery occlusion. The hypothesis ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05686070

NCT05686070 | A Study to Test Asundexian for Preventing ... The main purpose of this study is to learn whether asundexian works better than placebo at reducing ischemic strokes in participants who recently had a non- ...

5. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2022/08/27/04/10/PACIFIC-STROKE

AntiCoagulation via Inhibition of FXIa by the Oral ... The PACIFIC-Stroke trial showed that asundexian did not reduce the composite of covert brain infarction or ischemic stroke compared with placebo.

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061612

A Multicenter, Phase 2, Randomized, Placebo-Controlled ... Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 ...