BAY3018250 for Deep Vein Thrombosis

(SIRIUS Trial)

Recruiting at 102 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bayer

Must be taking: Low molecular weight heparins, DOACs

Must not be taking: Antiplatelet therapy, Antifibrinolytics

Disqualifiers: Pulmonary embolism, Active bleeding, Cancer, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

255 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for a better way to treat people who have deep vein thrombosis (DVT). DVT is a condition that occurs when a blood clot forms in a deep vein in the leg. DVT is called 'proximal' when the clot is formed in the veins of the hip, thigh, and knee. DVT can cause serious health problems. The blood clots in the veins can break loose and can then travel through the bloodstream and get stuck in the lungs, blocking blood flow to the lungs. Symptoms of DVT include swelling, pain, and tenderness in the affected leg, as well as redness and warmth in the area. Currently, DVT is usually treated using blood thinners to prevent the clot from getting bigger or breaking off and traveling to the lungs. However, blood thinners may not be able to remove a blood clot quickly and may not be suitable for everyone who has DVT. BAY3018250 is a drug that works by dissolving blood clots. In this study, researchers will compare BAY3018250 with placebo to learn how well it works and how safe it is in participants with proximal DVT. A placebo looks like the study drug but does not have any medicine in it. Using a placebo helps researchers to confirm that the results observed during the study were caused by the study drug and not by other factors. The main purposes of this study are to learn: * How well BAY3018250 works in dissolving blood clots in participants with proximal DVT and * How safe is BAY3018250 as a treatment for participants with proximal DVT? For this, the researchers will use ultrasound tests to measure blood clots in participants before and at various times after study treatment. They call these measurements a clot burden score. They will compare the clot burden score before and after treatment and will calculate a complex measure called AUC. This tells researchers how the clots have changed over time. And researchers will collect the number of bleeding events that require medical attention. The study participants will be randomly (by chance) assigned to one of 3 treatment groups. Dependent on the group, they will receive a single dose of high dose or low dose of BAY3018250 or placebo. Researchers will closely monitor participants for 90 days after receiving the study treatment. During the study, the doctors and their study team will: * take blood samples * do physical examinations * examine heart health using electrocardiogram (ECG) * check vital signs such as blood pressure, heart rate * undergo ultrasound tests to measure the blood clots * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments.

Will I have to stop taking my current medications?

The trial requires participants to be on certain blood thinners (low molecular weight heparins or direct oral anticoagulants) before joining. However, you cannot use antiplatelet therapy (except low-dose aspirin), antifibrinolytic drugs, or therapeutic antibodies during the study.

What data supports the effectiveness of the drug BAY3018250 for treating deep vein thrombosis?

Research shows that oral direct thrombin inhibitors and factor Xa inhibitors, which are types of blood thinners, can reduce major bleeding in deep vein thrombosis patients compared to traditional treatments. This suggests that similar drugs might be effective in managing this condition. ^{1 2 3 4 5}

How does the drug BAY3018250 differ from other treatments for deep vein thrombosis?

BAY3018250 is unique because it acts as a thromboxane A2-receptor antagonist, which means it blocks a specific receptor on platelets to reduce blood clot formation, unlike other treatments that typically target different pathways in the clotting process. ^{2 6 7 8 9}

Eligibility Criteria

This trial is for adults over 18 with recent proximal DVT, involving major leg veins, who are on certain blood thinners and weigh between 50-130 kg. It's not for those with pulmonary embolism, active bleeding risks, recent severe cardiovascular events or surgeries, active cancer treatment (except some skin cancers), or on other excluded medications.

Inclusion Criteria

Signed informed consent

I have a recent deep vein clot confirmed by an ultrasound.

I am on blood thinners like LMWHs or DOACs as prescribed.

Exclusion Criteria

I have a recent blood clot in my lungs causing symptoms.

I am not currently experiencing any active bleeding nor am I at high risk for bleeding.

I have not had a stroke, heart attack, brain bleed, or major surgery in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of high dose or low dose of BAY3018250 or placebo

1 day

1 visit (in-person)

Monitoring

Participants are monitored for safety and effectiveness, including blood samples, physical exams, ECG, vital signs, and ultrasound tests

90 days

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BAY3018250

Trial Overview The study tests BAY3018250's effectiveness in dissolving blood clots against a placebo in people with proximal DVT. Participants will be randomly assigned to receive either a high dose, low dose of the drug or a placebo once and monitored through various medical assessments over 90 days.

Participant Groups

Group I: BAY3018250 Dose 2 Experimental Treatment 1 Intervention

Participants will receive BAY3018250 Dose 2.

Group II: BAY3018250 Dose 1 Experimental Treatment 1 Intervention

Participants will receive BAY3018250 Dose 1.

Group III: Placebo to BAY3018250 Placebo Group 1 Intervention

Participants will receive placebo to BAY3018250.

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

Findings from Research

A systematic review comparing oral direct thrombin inhibitors and oral factor Xa inhibitors to conventional anticoagulants for treating deep vein thrombosis (DVT) was conducted, analyzing multiple studies to assess efficacy and safety.

The review found that both types of newer oral anticoagulants (direct thrombin and factor Xa inhibitors) are effective alternatives to traditional anticoagulants, potentially offering similar or improved outcomes for DVT treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In DVT, oral DTIs and factor Xa inhibitors reduce major bleeding but not recurrent VTE vs. conventional anticoagulants. Benz, AP., Eikelboom, JW.[2023]

In a randomized controlled trial involving patients with symptomatic isolated distal deep vein thrombosis, rivaroxaban treatment for six weeks was found to be effective, suggesting a shorter treatment duration may be sufficient.

The study compared the efficacy and safety of six weeks versus three months of rivaroxaban treatment, providing important insights into optimizing anticoagulant therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In symptomatic isolated DVT, 12 wk vs. 6 wk of rivaroxaban reduced recurrent VTE at 24 mo. DeLoughery, TG.[2023]

The JETi8 peripheral thrombectomy system demonstrated a high technical success rate of 76% in treating acute deep vein thrombosis (DVT) in a study of 18 patients, with an impressive mean thrombus reduction of 92%.

The overall procedural success rate was 100%, indicating that the JETi8 system is a safe and effective option for thrombectomy, with only one adverse event reported (a subsegmental pulmonary embolism).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Thrombectomy with the JETi8 Peripheral Thrombectomy System for the Treatment of Deep Vein Thrombosis. Cournoyer-Rodrigue, J., Bui, TB., Gilbert, P., et al.[2020]

In a long-term follow-up of 124 patients with acute deep-vein thrombosis, 42% had died within 6 to 8 years, with higher mortality rates in older patients and those with cancer or stroke, primarily due to cancer or cardiovascular disease.

While recurrent venous thromboembolism was relatively uncommon (15%), 42% of patients reported ongoing symptoms like pain and swelling in the affected leg, which were linked to poorer health-related quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of deep-vein thrombosis. Beyth, RJ., Cohen, AM., Landefeld, CS.[2006]

In a study of 387 patients with deep vein thrombosis (DVT), the development of post-thrombotic syndrome (PTS) was found to significantly lower quality of life (QOL) scores over a 2-year period, indicating that PTS is a major factor affecting long-term health outcomes.

Patients who developed PTS experienced less improvement in their QOL compared to those who did not, highlighting the importance of preventing and treating PTS to enhance patient well-being after a DVT diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of health-related quality of life during the 2 years following deep vein thrombosis. Kahn, SR., Shbaklo, H., Lamping, DL., et al.[2023]

Bay U3405, a thromboxane A2 receptor antagonist, significantly reduced thrombus formation in a baboon model, showing a 33% decrease in platelet deposition after 2 hours compared to control studies.

The treatment specifically inhibited platelet aggregation in response to collagen without affecting other coagulation tests, indicating its targeted mechanism of action in reducing arterial thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo inhibition of acute platelet-dependent thrombosis in a baboon model by Bay U3405, a thromboxane A2-receptor antagonist. Kotzé, HF., Lamprecht, S., Badenhorst, PN., et al.[2014]

In a study of 621 patients undergoing total knee replacement, the oral factor Xa inhibitor BAY 59-7939 demonstrated potential efficacy in preventing venous thromboembolism (VTE), with 31.7% to 40.4% of patients experiencing the primary efficacy endpoint across different doses, compared to 44.3% in the enoxaparin group.

The safety profile of BAY 59-7939 was acceptable, with major postoperative bleeding increasing with higher doses, but lower doses (2.5-10 mg b.i.d.) showed fewer bleeding events compared to higher doses, indicating a balance between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. Turpie, AG., Fisher, WD., Bauer, KA., et al.[2023]

In a study of 200 patients with deep vein thrombosis (DVT), those treated with novel oral anticoagulants (NOACs) like rivaroxaban and apixaban showed a significantly higher rate of blood vessel recanalization compared to those treated with conventional methods (low molecular weight heparin and vitamin K antagonists) after 180 days.

The average free lumen of blood vessels in the NOAC group was 85%, compared to 73% in the conventional treatment group, indicating that NOACs are a more effective option for treating DVT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recanalization rate of proximal deep venous thrombosis related to therapeutic modality during six months follow-up. Begić, A., Begić, E., Dilić, M., et al.[2022]

In a study of 543 patients with acute deep vein thrombosis, rivaroxaban showed a lower incidence of venous thromboembolic complications (5.4% to 6.6%) compared to standard therapy (9.9%) over 84 days, indicating its efficacy in treating this condition.

Rivaroxaban also demonstrated a favorable safety profile, with major and clinically relevant nonmajor bleeding occurring in 2.2% to 6.0% of patients, compared to 8.8% in those receiving standard therapy, suggesting it may be a safer alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. Buller, HR., Lensing, AW., Prins, MH., et al.[2022]

References

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

In DVT, oral DTIs and factor Xa inhibitors reduce major bleeding but not recurrent VTE vs. conventional anticoagulants. [2023]

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

In symptomatic isolated DVT, 12 wk vs. 6 wk of rivaroxaban reduced recurrent VTE at 24 mo. [2023]

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

Percutaneous Thrombectomy with the JETi8 Peripheral Thrombectomy System for the Treatment of Deep Vein Thrombosis. [2020]

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

Long-term outcomes of deep-vein thrombosis. [2006]

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

Determinants of health-related quality of life during the 2 years following deep vein thrombosis. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

In vivo inhibition of acute platelet-dependent thrombosis in a baboon model by Bay U3405, a thromboxane A2-receptor antagonist. [2014]

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

BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. [2023]

8. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Recanalization rate of proximal deep venous thrombosis related to therapeutic modality during six months follow-up. [2022]

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

A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. [2022]