Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters

Study Overview
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Brief Summary
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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.

Detailed Description
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TRIM-Line is a double blind randomized controlled trial comparing rivaroxaban 10mg po daily vs placebo in patients with active cancer and indwelling CVC. This will involve 9 centers across Canada.

Official Title
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Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters: a Randomized Controlled Trial

Conditions
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Venous Thromboembolism, Cancer

Intervention / Treatment
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* Drug: Rivaroxaban 10 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older with a new or existing diagnosis of cancer and a CVC inserted in the last 72 hours. Exclusion criteria: CVC in place for >72 hours Patient requires anticoagulation for other indications Concomitant use of dual antiplatelet therapy Major bleeding event in the last 4 weeks Patients receiving concomitant systemic treatment with strong inhibitors of both CYP 3A4 and P-gp (such as cobicistat, ketoconazole, itraconazole, posaconazole, or ritonavir). Known pregnancy or plan to become pregnant in next 3 months Severe renal insufficiency (Creatinine clearance <30 mL/min (defined by Cockcroft-Gault) in the previous 3 months Documented severe liver disease (e.g., acute clinical hepatitis, chronic active hepatitis or cirrhosis) in the previous 3 months Known thrombocytopenia (platelet count < 50x 109/L) in the previous 3 months Known allergy to rivaroxaban Life expectancy <3 months History of condition at increased bleeding risk including, but not limited to: cerebral infarction (hemorrhagic or ischemic), active peptic ulcer disease with recent bleeding, spontaneous or acquired impairment of hemostasis in the past 4 weeks. Chronic hemorrhagic disorder Primary malignancy diagnosis of basal cell or squamous cell carcinoma of the skin only Refused or unable to obtain consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Rivaroxaban 10mg OD | Drug: Rivaroxaban 10 MG<br>* Identical comparator drug<br>* Other names: Placebo;|
| Placebo Comparator: Control<br>Identical Placebo 10mg OD | Drug: Rivaroxaban 10 MG<br>* Identical comparator drug<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major VTE prevention | Number of Major VTE's in patient population | 90 days (± 3 days) of randomization | 
| Episodes of Major Bleeding | Number of participants who had a major bleed | 90 days (± 3 days) of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Clinically Relevant Non-Major Bleeding (CRNMB) | As defined by ISTH | 90 days (± 3 days) of randomization | 
| Number of patients who had a fatal VTE | Fatal VTE | 90 days (± 3 days) of randomization | 
| Number of patients who benefitted from using the experimental intervention | Composite of major VTE and major bleeding | 90 days (± 3 days) of randomization | 
| PE | Incidental and Symptomatic | 90 days (± 3 days) of randomization | 
| Proximal CVC VTE | Incidental and symptomatic proximal (axillary vein or more proximal) upper extremity CVC-related DVT | 90 days (± 3 days) of randomization | 
| Distal CVC VTE | Incidental and symptomatic distal (brachial vein) or proximal (axillary vein or more proximal) upper extremity CVC-related DVT | 90 days (± 3 days) of randomization | 
| Proximal Lower extremity DVT | Incidental and symptomatic proximal (popliteal vein or more proximal) lower extremity DVT | 90 days (± 3 days) of randomization | 
| Distal Lower extremity DVT | Incidental and symptomatic distal or proximal (popliteal vein or more proximal) lower extremity DVT | 90 days (± 3 days) of randomization | 
| Number of participants with Unusual site thrombosis including: splanchnic vein (portal, splenic, superior mesenteric, inferior mesenteric, hepatic) cerebral vein, renal or gonadal vein thromboses | Unusual site thrombosis including: splanchnic vein (portal, splenic, superior mesenteric, inferior mesenteric, hepatic) cerebral vein, renal or gonadal vein thromboses | 90 days (± 3 days) of randomization | 
| Number of participants with Superficial upper or lower extremity vein thrombosis | Superficial upper or lower extremity vein thrombosis | 90 days (± 3 days) of randomization | 
| Number of participants with an arterial thromboembolic event including: MI, stroke, peripheral arterial disease | Arterial thromboembolic events defined as a diagnostically confirmed final clinical diagnosis of myocardial infarction, stroke or peripheral arterial disease involving the following arterial vascular beds: carotid, upper or lower extremity, gastrointestinal tract, liver, spleen, or kidney | 90 days (± 3 days) of randomization | 
| CVC Life-span | Life span of inserted CVC | 90 days (± 3 days) of randomization | 
| Number of patients with CVC occlusion occurring after the start of therapy, defined as an obstruction of the CVC lumen that prevents or limits the ability to flush, withdraw blood and/or administer solutions or medications. | CVC occlusion occurring after the start of therapy, defined as an obstruction of the CVC lumen that prevents or limits the ability to flush, withdraw blood and/or administer solutions or medications. | 90 days (± 3 days) of randomization | 
| Number of patients with CVC-related blood stream infection defined as the presence of bacteremia originating from the CVC according to the definition from the Centers for Disease Control and Prevention | CVC-related blood stream infection defined as the presence of bacteremia originating from the CVC according to the definition from the Centers for Disease Control and Prevention | 90 days (± 3 days) of randomization | 
| Number of participants who passed away during the trial | Overall mortality | 90 days (± 3 days) of randomization | 
| EQ-5D-5L Health-related quality of life | Health-related quality of life | 90 days (± 3 days) of randomization | 
| ICER | Incremental cost-effectiveness ratio (ICER) at one year | 1 Year |