Clinical trial NCT05029063: Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters
Official title: Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Venous Thromboembolism
Cancer
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2021-08-31
Enrollment: 1828
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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:

1. CVC in place for \>72 hours
2. Patient requires anticoagulation for other indications
3. Concomitant use of dual antiplatelet therapy
4. Major bleeding event in the last 4 weeks
5. Patients receiving concomitant systemic treatment with strong inhibitors of both CYP 3A4 and P-gp (such as cobicistat, ketoconazole, itraconazole, posaconazole, or ritonavir).
6. Known pregnancy or plan to become pregnant in next 3 months
7. Severe renal insufficiency (Creatinine clearance \<30 mL/min (defined by Cockcroft-Gault) in the previous 3 months
8. Documented severe liver disease (e.g., acute clinical hepatitis, chronic active hepatitis or cirrhosis) in the previous 3 months
9. Known thrombocytopenia (platelet count \< 50x 109/L) in the previous 3 months
10. Known allergy to rivaroxaban
11. Life expectancy \<3 months
12. History of condition at increased bleeding risk including, but not limited to:

    1. cerebral infarction (hemorrhagic or ischemic), active peptic ulcer disease with recent bleeding, spontaneous or acquired impairment of hemostasis in the past 4 weeks.
    2. Chronic hemorrhagic disorder
13. Primary malignancy diagnosis of basal cell or squamous cell carcinoma of the skin only
14. Refused or unable to obtain consent

Primary outcomes:
measure: Major VTE prevention
timeFrame: 90 days (± 3 days) of randomization
measure: Episodes of Major Bleeding
timeFrame: 90 days (± 3 days) of randomization
Secondary outcomes:
measure: Number of participants with Clinically Relevant Non-Major Bleeding (CRNMB)
timeFrame: 90 days (± 3 days) of randomization
measure: Number of patients who had a fatal VTE
timeFrame: 90 days (± 3 days) of randomization
measure: Number of patients who benefitted from using the experimental intervention
timeFrame: 90 days (± 3 days) of randomization
measure: PE
timeFrame: 90 days (± 3 days) of randomization
measure: Proximal CVC VTE
timeFrame: 90 days (± 3 days) of randomization
measure: Distal CVC VTE
timeFrame: 90 days (± 3 days) of randomization
measure: Proximal Lower extremity DVT
timeFrame: 90 days (± 3 days) of randomization
measure: Distal Lower extremity DVT
timeFrame: 90 days (± 3 days) of randomization
measure: Number of participants with Unusual site thrombosis including: splanchnic vein (portal, splenic, superior mesenteric, inferior mesenteric, hepatic) cerebral vein, renal or gonadal vein thromboses
timeFrame: 90 days (± 3 days) of randomization
measure: Number of participants with Superficial upper or lower extremity vein thrombosis
timeFrame: 90 days (± 3 days) of randomization
measure: Number of participants with an arterial thromboembolic event including: MI, stroke, peripheral arterial disease
timeFrame: 90 days (± 3 days) of randomization
measure: CVC Life-span
timeFrame: 90 days (± 3 days) of randomization
measure: 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.
timeFrame: 90 days (± 3 days) of randomization
measure: 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
timeFrame: 90 days (± 3 days) of randomization
measure: Number of participants who passed away during the trial
timeFrame: 90 days (± 3 days) of randomization
measure: EQ-5D-5L Health-related quality of life
timeFrame: 90 days (± 3 days) of randomization
measure: ICER
timeFrame: 1 Year
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: HHS - Juravinski Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute- The Ottawa Hospital
state: Ontario
city: Sault Ste Marie
country: Canada
facility: Sault Area Hospital
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS Montérégie-Centre HOPITAL CHARLES LEMOYNE
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Dr. Marc Carrier
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ikesaka R, Siegal D, Mallick R, Wang TF, Witham D, Webb C, Carrier M; Canadian Venous Thromboembolism Research Network (CanVECTOR). Thromboprophylaxis with rivaroxaban in patients with malignancy and central venous lines (TRIM-Line): A two-center open-label pilot randomized controlled trial. Res Pract Thromb Haemost. 2021 May 5;5(4):e12517. doi: 10.1002/rth2.12517. eCollection 2021 May.