Rivaroxaban for Cancer-related Blood Clot Prevention

(TRIM-Line Trial)

Recruiting at 6 trial locations

Overseen By Amanda Pecarskie

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Dual antiplatelets, CYP 3A4 inhibitors

Disqualifiers: Pregnancy, Renal insufficiency, Liver disease, 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: 90 days

1828 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the full trial is to determine the efficacy and safety of prophylactic dose rivaroxaban to prevent VTE among cancer patients with CVC.

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 are on certain strong medications like cobicistat or ketoconazole, or if you need dual antiplatelet therapy.

What data supports the effectiveness of the drug Rivaroxaban for cancer-related blood clot prevention?

Research shows that Rivaroxaban, a drug used to prevent blood clots, is effective and safe for cancer patients with blood clot issues, similar to other treatments like low-molecular-weight heparins. It has been shown to prevent recurrent blood clots in cancer patients without increasing major bleeding risks. ^{1 2 3 4 5}

Is Rivaroxaban safe for humans?

Rivaroxaban, also known as Xarelto, has been studied in over 24,000 patients for various conditions, including cancer-related blood clots. It is generally considered safe, but bleeding is a known side effect, especially in patients with cancer. It offers benefits like once-daily dosing and fewer drug interactions compared to older treatments. ^{1 2 6 7 8}

How is the drug Rivaroxaban unique for preventing cancer-related blood clots?

Rivaroxaban is unique because it is an oral direct Factor Xa inhibitor that simplifies treatment by not requiring routine blood monitoring, unlike traditional vitamin K antagonists. It offers a convenient once-daily dosing and has fewer food and drug interactions, making it a potentially attractive alternative for preventing blood clots in cancer patients. ^{4 7 9 10 11}

Research Team

Marc Carrier, MD

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults over 18 with any type of cancer who have had a central venous catheter (CVC) placed in the last 72 hours. It's not suitable for those with severe liver disease, low platelets, CVC older than 72 hours, other anticoagulation needs, recent major bleeding, pregnancy plans within three months, certain skin cancers only, life expectancy under three months or known allergies to rivaroxaban.

Inclusion Criteria

I am 18 or older with cancer and had a central venous catheter placed within the last 3 days.

Exclusion Criteria

Your platelet count has been very low in the past 3 months.

You are allergic to rivaroxaban.

You are not expected to live for more than 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rivaroxaban 10mg daily or placebo for the prevention of VTE

90 days

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Rivaroxaban

Trial Overview The trial tests if a blood thinner called Rivaroxaban can prevent blood clots in cancer patients who have a CVC. The goal is to see how effective and safe this medication is at stopping clots from forming without causing too many side effects.

Participant Groups

Group I: Experimental Experimental Treatment 1 Intervention

Rivaroxaban 10mg OD

Group II: Control Placebo Group 1 Intervention

Identical Placebo 10mg OD

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

Approved in United States as Xarelto for:

• Deep vein thrombosis (DVT)
• Venous thromboembolism (VTE)
• Stroke prevention in non-valvular atrial fibrillation
• Prevention of VTE in patients undergoing knee or hip replacement surgery

Approved in European Union as Xarelto for:

• Deep vein thrombosis (DVT)
• Venous thromboembolism (VTE)
• Stroke prevention in non-valvular atrial fibrillation
• Prevention of VTE in patients undergoing knee or hip replacement surgery
• Prevention of atherothrombotic events in patients with acute coronary syndrome

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Findings from Research

In a study of 400 patients with active cancer and venous thromboembolism, rivaroxaban demonstrated a low recurrence rate of 3.25% for symptomatic VTE, indicating its efficacy as an anticoagulant in this population.

The safety profile of rivaroxaban was acceptable, with major bleeding incidents occurring in 5.5% of patients during treatment, suggesting it can be a viable option for managing cancer-associated thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Rivaroxaban for the Treatment of Symptomatic Venous Thromboembolism in 400 Patients With Active Cancer: A Single-Center Experience. Pignataro, BS., Nishinari, K., Cavalcante, RN., et al.[2018]

In a study of 144 adult patients with solid tumor malignancies receiving rivaroxaban, 44% experienced bleeding incidents, indicating a significant risk associated with this anticoagulant therapy.

Specific cancer types, including bladder, breast, melanoma, pancreas, prostate, and renal cell cancers, showed higher incidences of both major and minor bleeding, suggesting that these patients may require closer monitoring while on rivaroxaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of bleeding incidences associated with rivaroxaban therapy in adults with solid tumors. Weddle, KJ., Kiel, PJ., Patel, PJ.[2019]

In a study of 127 oncology patients with venous thromboembolism, oral factor Xa inhibitors (rivaroxaban/apixaban) showed no significant difference in recurrence rates compared to warfarin and enoxaparin after three months, indicating their potential effectiveness in this population.

The study also found that major bleeding was rare, occurring in only one patient on enoxaparin, and mortality rates were lowest in the oral factor Xa inhibitor group, suggesting a favorable safety profile, but further randomized trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study. Alzghari, SK., Seago, SE., Garza, JE., et al.[2018]

This study is investigating the effects of Rivaroxaban, a direct oral anticoagulant, on early breast cancer patients, specifically looking at its potential to inhibit tumor growth and progression in estrogen receptor-negative cases, which are known to have a poorer prognosis.

Eighty-eight treatment-naïve early breast cancer patients will be randomized to receive Rivaroxaban or no treatment for 11 to 17 days before surgery, with the primary goal of measuring changes in tumor proliferation (Ki67) and secondary outcomes related to cancer progression and coagulation markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban compared to no treatment in ER-negative stage I-III early breast cancer patients (the TIP Trial): study protocol for a phase II preoperative window-of-opportunity study design randomised controlled trial. Castle, J., Blower, E., Bundred, NJ., et al.[2021]

Direct oral anticoagulants, particularly rivaroxaban, have been shown to be as effective and safe as traditional vitamin K antagonists for treating and preventing thrombosis in cancer patients, based on recent randomized clinical trials.

Rivaroxaban is now considered a viable alternative to low-molecular-weight heparins for managing cancer-associated venous thromboembolic complications, as supported by significant clinical evidence and guidelines from the International Society on Thrombosis and Hemostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Venous thromboembolic complications in oncological patients: present-day possibilities of effective and safe anticoagulant therapy]. Fokin, AA., Bagaev, KV.[2020]

In a study of 296 patients treated with rivaroxaban for venous thromboembolism, those with active malignancy had similar rates of recurrence (3.3%) compared to those without cancer (2.8%), indicating that rivaroxaban is effective in both groups.

While rivaroxaban showed comparable safety profiles, there were borderline higher rates of major and nonmajor clinically relevant bleeding in patients with cancer, suggesting a need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rivaroxaban in Patients with Venous Thromboembolism and Active Malignancy: A Single-Center Registry. Bott-Kitslaar, DM., Saadiq, RA., McBane, RD., et al.[2022]

Rivaroxaban is a direct factor Xa inhibitor that offers a simplified alternative to traditional vitamin K antagonists like warfarin, allowing for once-daily dosing without the need for frequent monitoring or dose adjustments.

In phase-II and phase-III trials involving over 24,000 patients, rivaroxaban has demonstrated safety and efficacy for preventing and treating venous thromboembolism, and is also being studied for other conditions like pulmonary embolism and stroke prevention in atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral direct factor Xa inhibitors, with special emphasis on rivaroxaban. Mousa, SA.[2015]

In a study of 193 patients with venous thromboembolism (VTE) and active cancer, rivaroxaban demonstrated acceptable effectiveness, with similar rates of VTE recurrence and major bleeding compared to 823 patients without active cancer.

However, patients with active cancer had a significantly higher all-cause mortality rate (23.29% vs. 2.03% per patient-year), indicating that while rivaroxaban is effective, the underlying cancer poses a greater risk to patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study. Hisatake, S., Ikeda, T., Fukuda, I., et al.[2023]

Rivaroxaban, a direct Factor Xa inhibitor, has been evaluated in over 24,000 patients across Phase II and III trials for its safety and efficacy in preventing and treating venous thromboembolism, showing promise as an alternative to traditional vitamin K antagonists like warfarin.

The drug is also being studied for various conditions, including pulmonary embolism and stroke prevention in patients with non-valvular atrial fibrillation, indicating its potential broad application in thrombosis management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban, an oral direct factor Xa inhibitor. Piccini, JP., Patel, MR., Mahaffey, KW., et al.[2019]

Rivaroxaban is an effective oral medication that inhibits Factor Xa, showing significant efficacy in preventing and treating thromboembolic disorders, including venous thromboembolism after major orthopedic surgery.

In phase III studies, rivaroxaban was found to be more effective than enoxaparin for preventing blood clots after knee surgery, with a similar low risk of bleeding, making it a promising alternative to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban. A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. Perzborn, E., Kubitza, D., Misselwitz, F.[2015]

Rivaroxaban is a direct factor Xa inhibitor that is effective in preventing venous thromboembolism in patients undergoing elective knee or hip replacement surgery, with a recommended dose of 10 mg per day.

In patients with non-valvular atrial fibrillation, rivaroxaban (20 mg per day) is approved for stroke prevention, and its low dose (2.5 mg twice daily) has shown promise in reducing cardiovascular events in those with recent acute coronary syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rivaroxaban in the prevention and treatment of thromboembolic disorders]. Helbing, T., Bode, C., Moser, M.[2015]

References

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

Oral Rivaroxaban for the Treatment of Symptomatic Venous Thromboembolism in 400 Patients With Active Cancer: A Single-Center Experience. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Assessment of bleeding incidences associated with rivaroxaban therapy in adults with solid tumors. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Rivaroxaban compared to no treatment in ER-negative stage I-III early breast cancer patients (the TIP Trial): study protocol for a phase II preoperative window-of-opportunity study design randomised controlled trial. [2021]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Venous thromboembolic complications in oncological patients: present-day possibilities of effective and safe anticoagulant therapy]. [2020]

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

Efficacy and Safety of Rivaroxaban in Patients with Venous Thromboembolism and Active Malignancy: A Single-Center Registry. [2022]

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

Oral direct factor Xa inhibitors, with special emphasis on rivaroxaban. [2015]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Rivaroxaban, an oral direct factor Xa inhibitor. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Rivaroxaban. A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

[Rivaroxaban in the prevention and treatment of thromboembolic disorders]. [2015]