Anticoagulation Strategies for Blood Clots in Cancer Patients
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen byTzu-Fei Wang, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
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
Prior Safety Data
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.
12345Is 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.
12678How 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.
128910Eligibility 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.
+1 more
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.
+6 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Modified dose LMWH without platelet transfusion supportExperimental Treatment3 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 supportActive Control3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Windsor Regional HospitalWindsor, Canada
The Ottawa HospitalOttawa, Canada
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Who Is Running the Clinical Trial?
Ottawa Hospital Research InstituteLead Sponsor
References
Management of venous thromboembolism in patients with cancer: role of dalteparin. [2021]Cancer is a major risk factor for the development of venous thromboembolism (VTE). Conventional anticoagulant therapy with a vitamin K antagonist is more problematic in cancer patients due to an increased risk of recurrent VTE, and an increased risk of anticoagulant-related bleeding. In recent years, there has been a shift toward treating cancer patients with VTE with extended duration dalteparin. Dalteparin, a low-molecular-weight heparin, has been shown to be more effective, and as safe as conventional anticoagulant therapy, in cancer patients with VTE. This paper will (a) review the relationship between cancer and VTE, and (b) provide an overview of the role of dalteparin in the management of VTE in patients with cancer.
Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis. [2021]International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE.
Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. [2018]In the initial treatment of venous thromboembolism (VTE) fondaparinux, a pentasaccharide, is a good alternative to heparin. Whether this is also true for cancer patients is unknown. We performed two post-hoc analyses of two randomized studies to compare efficacy, safety and overall survival of fondaparinux to standard initial (low-molecular-weight) heparin (LMWH) treatment in cancer patients with venous thromboembolism. Two hundred thirty-seven cancer patients with deep venous thrombosis (DVT) were initially treated with fondaparinux or enoxaparin. Two hundred forty cancer patients with pulmonary embolism (PE) received fondaparinux or unfractionated heparin. The initial treatment was followed by vitamin K antagonists. In DVT patients, the three-month recurrence rate was 5.4% in the enoxaparin recipients compared to 12.7% in those treated with fondaparinux [absolute difference 7.3%, 95% CI 0.1, 14.5]. A recurrence was observed in 8.9% of the PE patients treated with fondaparinux compared to 17.2% in the unfractionated heparin recipients [absolute difference -8.3, 95% CI -16.7, 0.1]. In both studies no difference in bleeding and overall survival was observed. Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients. No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH. Because of study limitations these results should be considered hypothesis-generating.
Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. [2022]Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial.
The Efficacy and Safety of Rivaroxaban and Dalteparin in the Treatment of Cancer Associated Venous Thrombosis. [2020]Venous thromboembolism (VTE) is a complication of malignancy that is associated with significant mortality. The CLOT trial showed superiority of dalteparin in comparison to warfarin in preventing VTE recurrence. Rivaroxaban has been approved for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). In the absence of large randomized trials in the oncology population, the efficacy and safety of rivaroxaban for the treatment of VTE in cancer patients needs to be assessed. A single-center retrospective chart review was conducted to assess the efficacy and safety of rivaroxaban compared with dalteparin in cancer-associated thrombosis. Out of 671 patients identified, 286 patients (107 in the rivaroxaban group and 179 in the dalteparin group) were eligible for analysis. The rivaroxaban group had a rate of VTE recurrence at 6 months of 4.9 versus 11.1% with dalteparin (p = 0.252). The incidence of recurrent DVT at 6 months was lower in patients treated with rivaroxaban (0%) compared with dalteparin (8.2%) at 6 months (p = 0.025). Incidence of recurrent PE in the rivaroxaban group (5%) versus dalteparin group (3.1%) at 6 months was not statistically significant (p = 0.675). No significant difference was identified between the rivaroxaban group and dalteparin group in the rate of major bleeding (2.8 vs. 1.1%, respectively). Rivaroxaban was comparable to dalteparin in prevention of VTE recurrence while having no significant differences with major or minor bleeding.
Comparative effectiveness of dalteparin and enoxaparin in a hospital setting. [2013]This study compared the effectiveness of a change from enoxaparin to dalteparin for the prophylaxis of patients at risk of venous thromboembolism (VTE).
Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. [2019]Low molecular weight heparins (LMWHs) and fondaparinux are widely used for prophylaxis and treatment of venous thromboembolic disease in cancer patients. However, the optimization of the antithrombotic treatment especially in patients with adenocarcinoma of the pancreas is a challenging issue. The understanding of the mechanism of action of the LMWHs and fondaparinux in cancer-induced hypercoagulability might help to optimize antithrombotic treatment. To this aim, we investigated the influence of BXPC3 pancreas adenocarcinoma cells on the antithrombotic activity of LMWHs and fondaparinux. Thrombin generation (TG) in normal platelet poor (PPP) and platelet rich plasma (PRP) spiked with clinically relevant concentrations of dalteparin, enoxaparin, nadroparin tinzaparin and fondaparinux was assessed with the Calibrated Automated Thrombogram assay. BXPC3 (5 cells/μl) were added to plasma. The mean rate index (MRI) of the propagation phase of TG and the endogenous thrombin potential (ETP) were analyzed. The IC50 of the studied compounds were determined and compared on the basis of anti-Xa and anti-IIa equivalent units. We demonstrate that the specific antithrombin (AT)-dependent anti-Xa activity of LMWHs and fondaparinux almost selectively inhibits the propagation phase of TG. The synergy between the anti-Xa and anti-IIa activities of LMWHs rather than the selective inhibition of FXa warrants abrogation of TG. The mean molecular weight and anti-Xa/anti-IIa ratio of the AT-dependent agents cannot predict the alteration of their capacity to inhibit TG. Tinzaparin was the most potent inhibitor of TG than the other LMWHs. Enoxaparin was more potent than nadroparin and dalteparin.
OC-11 - Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. [2016]Venous thromboembolism (VTE) in cancer patients is an increasingly frequent clinical problem. The overall impact of VTE on cancer patients can be considerable. Targeted patient selection by identifying patients with clinically significant recurrent VTE may have wider health economic benefits whilst reducing patient risk through over-treatment. In the UK, dalteparin is one licensed anticoagulant for the extended treatment and prevention of recurrence of VTE in cancer patients. Rivaroxaban is a highly selective direct Factor Xa inhibitor with oral bioavailability.
Can we optimise treatment of thrombosis? [2019]The occurrence of thromboembolism in patients with cancer complicates their management. Patients with cancer who have established venous thrombosis are at increased risk of recurrent venous thromboembolism and anticoagulant-associated bleeding compared with non-cancer patients. Low-molecular-weight heparins have largely replaced unfractionated heparin as the initial treatment for acute thrombosis and have the advantage that they can be administered at home. The use of oral anticoagulant for the long-term secondary prevention of recurrent venous thromboembolism can be problematic in the cancer patient due to unpredictable changes in the dose response because of poor nutrition, infection, concomitant medications and impaired hepatic function. A large randomised clinical trial has shown that 6 months of treatment with the low-molecular-weight heparin dalteparin in place of 6 months of oral anticoagulant therapy significantly reduces the risk of recurrent thrombosis (50% reduction in risk; p = 0.0017) in cancer patients without an increase in bleeding.
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]Cancer patients have a four- to fivefold greater risk of thrombosis than the general population. Recommended treatment for cancer-associated thrombosis is 3-6 months of low-molecular-weight heparin. The 'select-d' trial is an open-label, randomised, multi-centre pilot trial in patients with cancer-associated thrombosis, utilising dalteparin (low-molecular-weight heparin) versus rivaroxaban (a direct oral anticoagulant), to assess effectiveness and safety.