Anticoagulation Strategies for Blood Clots in Cancer Patients

Recruiting at 2 trial locations

Overseen By Jennifer Brinkhurst

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must be taking: Blood thinners

Must not be taking: Anticoagulants

Disqualifiers: Short life expectancy, Low creatinine, 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

Compensation: Varies

Number of Visits: 2

Duration: 14 days

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with cancer are prone to have blood clots, which are usually treated with blood thinners. The main complication of blood thinners is bleeding. This is especially a concern when the number of platelets in the blood is lower than 50,000 per microliter. The role of platelets is to stop bleeding, so when the number of platelets is low, patients are at a higher risk of bleeding. Cancer patients are prone to have lower platelet numbers due to cancer therapies and/or cancer itself. It is not clear what the best treatment is for cancer patients who need blood thinners for a blood clot but have low platelet counts. The investigators plan to do a small study called a pilot study to help plan for a larger study in such patients. In the pilot study, investigators will include 50 patients with cancer, low platelet counts, and a blood clot diagnosed within 4 weeks. Patients will be randomly assigned to one of the two treatment strategies: the full dose of blood thinners along with platelet transfusion or a reduced dose of blood thinners without platelet transfusion. The investigators will follow all patients for 90 days. If this pilot study is successful, it will help lead to a much larger trial, which will provide important information on the best treatment strategy in these patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Dalteparin for treating blood clots in cancer patients?

Research shows that Dalteparin, a type of low-molecular-weight heparin, is more effective and as safe as traditional anticoagulant therapy in preventing blood clot recurrence in cancer patients. It has been shown to be superior to warfarin in preventing VTE recurrence, making it a recommended option for treating blood clots in these patients. ^{1 2 3 4 5}

Is the anticoagulation treatment safe for cancer patients?

Dalteparin, a type of low-molecular-weight heparin, has been shown to be as safe as traditional anticoagulant therapy for cancer patients with blood clots, with no increased risk of bleeding compared to other treatments. ^{1 2 6 7 8}

How is the drug Dalteparin different from other treatments for blood clots in cancer patients?

Dalteparin, a low-molecular-weight heparin, is unique because it can be administered at home and has been shown to significantly reduce the risk of recurrent blood clots in cancer patients without increasing bleeding risk, compared to traditional oral anticoagulants. ^{1 2 8 9 10}

Research Team

Marc Carrier, MD

Principal Investigator

Ottawa Hospital Research Institute

Tzu-Fei Wang, MD

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults over 18 with active cancer and a low platelet count due to cancer or its treatment. They must have had a blood clot within the last two weeks and be able to give consent. People can't join if they've been on blood thinners for more than 72 hours, expect to live less than a month, have severe kidney issues, are allergic to heparin products, have other causes of low platelets, refuse blood products, or where any anticoagulation is unsafe.

Inclusion Criteria

Able to provide written informed consent

I am an adult with cancer diagnosed or treated in the last 6 months, or it's getting worse.

My platelet count is below 50,000 due to cancer or its treatment.

Exclusion Criteria

I have a clot in a vein near the surface of my body.

I have a low platelet count not caused by common blood disorders.

My body has resisted platelet transfusions due to HLA antibodies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either modified dose LMWH without platelet transfusion or higher dose LMWH with platelet transfusion support for 14 days.

14 days

Daily visits for inpatients or at least 2 times a week for outpatients

Transition

After Day 14, patients transition to modified dose LMWH without platelet transfusion.

76 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including clinical outcomes and feasibility measures.

90 days

Treatment Details

Interventions

• Dalteparin
• Enoxaparin
• Tinzaparin

Trial Overview The study tests two strategies in patients with cancer who also have clots and low platelets: one group will receive full-dose blood thinners plus platelet transfusions; the other gets reduced-dose thinners without transfusions. The goal is to find out which method works best without causing excessive bleeding.

Participant Groups

Group I: Modified dose LMWH without platelet transfusion support Experimental Treatment 3 Interventions

Patients will be given modified dose LMWH as below based on the first platelet count of the day (daily in admitted patients or at least 2 times a week in outpatients), without empiric platelet transfusion: I. Platelet count 25-50,000/µL: 50% dose LMWH II. Platelet count \< 25,000/µL: hold anticoagulation

Group II: Higher dose LMWH with platelet transfusion support Active Control 3 Interventions

Patients assigned to higher dose LMWH (see below) will be given transfusion for 14 days when the first platelet count of the day falls below 50,000/uL (daily inpatient or at least 2 times a week in outpatients). Post-transfusion counts will not be routinely obtained unless clinically indicated I. Platelet count 25-50,000/µL: platelet transfusion + 100% dose LMWH II. Platelet count \< 25,000/µL: platelet transfusion + 50% dose LMWH After Day 14, patients will be transitioned to modified dose LMWH as the other arm without platelet transfusion. LMWH can include enoxaparin, dalteparin, or tinzaparin, with 100% as: * Enoxaparin - 1mg/kg subcutaneously twice daily * Dalteparin - 200 IU/kg subcutaneously daily for 1 month then 150 U/kg daily * Tinzaparin - 175 units/kg subcutaneously daily

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

Approved in European Union as Fragmin for:

• Prevention of deep vein thrombosis
• Treatment of deep vein thrombosis
• Prevention of pulmonary embolism
• Treatment of unstable angina and non-Q-wave myocardial infarction

Approved in United States as Fragmin for:

• Prevention of deep vein thrombosis
• Treatment of acute deep vein thrombosis
• Extended treatment of deep vein thrombosis
• Prevention of ischemic complications in unstable angina and non-Q-wave myocardial infarction

Approved in Canada as Fragmin for:

• Prevention of deep vein thrombosis
• Treatment of deep vein thrombosis
• Prevention of pulmonary embolism

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Findings from Research

Cancer significantly increases the risk of developing venous thromboembolism (VTE), making effective treatment crucial for affected patients.

Dalteparin, a low-molecular-weight heparin, has been found to be more effective and as safe as traditional vitamin K antagonists for treating VTE in cancer patients, addressing the challenges of recurrent VTE and bleeding risks associated with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of venous thromboembolism in patients with cancer: role of dalteparin. Linkins, LA.[2021]

In a meta-analysis of four randomized controlled trials involving 2,894 patients, direct oral anticoagulants (DOACs) like apixaban, edoxaban, and rivaroxaban significantly reduced the risk of recurrent venous thromboembolism (VTE) in cancer patients compared to low-molecular-weight heparin (LMWH), with a relative risk of 0.62.

The use of DOACs did not result in a significantly higher risk of major bleeding compared to LMWH, indicating that they are a safe and effective alternative for treating cancer-associated VTE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis. Giustozzi, M., Agnelli, G., Del Toro-Cervera, J., et al.[2021]

In a study of 237 cancer patients with deep venous thrombosis (DVT) and 240 with pulmonary embolism (PE), fondaparinux showed a higher recurrence rate of DVT (12.7%) compared to enoxaparin (5.4%), but a lower recurrence rate for PE (8.9%) compared to unfractionated heparin (17.2%).

Overall, fondaparinux was found to have comparable safety and overall survival rates to standard treatments (enoxaparin and unfractionated heparin) in cancer patients, indicating it may be a viable alternative for initial VTE treatment, although the results should be interpreted cautiously due to study limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. van Doormaal, FF., Raskob, GE., Davidson, BL., et al.[2018]

In a study involving 900 patients with active cancer and acute venous thromboembolism (VTE), tinzaparin showed a lower cumulative incidence of recurrent VTE (7.2%) compared to warfarin (10.5%), although this difference was not statistically significant (P=0.07).

Tinzaparin was associated with a significantly lower rate of clinically relevant nonmajor bleeding compared to warfarin (11% vs 15.3%, P=0.004), while there were no significant differences in major bleeding or overall mortality between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. Lee, AYY., Kamphuisen, PW., Meyer, G., et al.[2022]

In a study of 286 cancer patients with venous thromboembolism, rivaroxaban showed a lower rate of recurrent deep vein thrombosis (DVT) at 6 months (0%) compared to dalteparin (8.2%), indicating it may be more effective for this specific complication.

Rivaroxaban and dalteparin had similar rates of major bleeding (2.8% vs. 1.1%), suggesting that rivaroxaban is as safe as dalteparin for treating VTE in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Rivaroxaban and Dalteparin in the Treatment of Cancer Associated Venous Thrombosis. Chaudhury, A., Balakrishnan, A., Thai, C., et al.[2020]

A study of 7022 hospitalized patients showed that switching from enoxaparin to dalteparin for preventing venous thromboembolism (VTE) resulted in similar effectiveness in VTE rates, in-hospital length of stay, readmittance, and bleeding rates.

The change to dalteparin not only maintained efficacy but also led to significant cost savings of $40,788 over six months, making it a viable alternative for VTE prophylaxis in hospitals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of dalteparin and enoxaparin in a hospital setting. Carson, W., Schilling, B., Simons, WR., et al.[2013]

In a study investigating the effects of low molecular weight heparins (LMWHs) and fondaparinux on thrombin generation in the presence of pancreatic adenocarcinoma cells, it was found that these anticoagulants primarily inhibit the propagation phase of thrombin generation, which is crucial in managing cancer-related blood clotting issues.

Among the LMWHs tested, tinzaparin was identified as the most effective in inhibiting thrombin generation, outperforming other LMWHs like enoxaparin, nadroparin, and dalteparin, suggesting that specific LMWHs may be better suited for optimizing antithrombotic treatment in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. Gerotziafas, GT., Galea, V., Mbemba, E., et al.[2019]

The select-d trial is a pioneering study comparing the effectiveness of rivaroxaban and dalteparin in preventing recurrent venous thromboembolism (VTE) in cancer patients, with 530 participants being recruited to ensure reliable outcome estimates.

Preliminary data shows that most participants have solid tumors, with a significant portion presenting with incidental pulmonary embolism, highlighting the need for targeted treatment strategies in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OC-11 - Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. Young, A., Phillips, J., Hancocks, H., et al.[2016]

A large randomized clinical trial demonstrated that using the low-molecular-weight heparin dalteparin for 6 months significantly reduces the risk of recurrent venous thromboembolism in cancer patients by 50% compared to oral anticoagulants.

Dalteparin treatment does not increase the risk of bleeding, making it a safer alternative for managing thromboembolism in patients with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can we optimise treatment of thrombosis? Levine, MN.[2019]

Cancer patients are at a significantly higher risk of thrombosis, yet many are unaware of this risk, highlighting the need for better education and prompt treatment options.

In a study of 37 cancer patients, most preferred oral anticoagulants like rivaroxaban over injections, suggesting that if safety and efficacy are comparable, tablets could improve patient adherence and satisfaction with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral anticoagulation is preferable to injected, but only if it is safe and effective: An interview study of patient and carer experience of oral and injected anticoagulant therapy for cancer-associated thrombosis in the select-d trial. Hutchinson, A., Rees, S., Young, A., et al.[2021]

References

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

Management of venous thromboembolism in patients with cancer: role of dalteparin. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. [2018]

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

Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. [2022]

5. India pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Rivaroxaban and Dalteparin in the Treatment of Cancer Associated Venous Thrombosis. [2020]

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

Comparative effectiveness of dalteparin and enoxaparin in a hospital setting. [2013]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. [2019]

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

OC-11 - Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. [2016]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Can we optimise treatment of thrombosis? [2019]

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

Oral anticoagulation is preferable to injected, but only if it is safe and effective: An interview study of patient and carer experience of oral and injected anticoagulant therapy for cancer-associated thrombosis in the select-d trial. [2021]