Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters (TRIM-Line)

Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters: a Randomized Controlled 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.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban 10 MG

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.

• Study Type: Interventional
• Enrollment (Estimated): 1828
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bashour Yazji; Phone Number: 73958 613-737-8899; Email: byazji@ohri.ca

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Recruiting
      • Nova Scotia Health
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Recruiting
      • William Osler Health System
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • HHS - Juravinski Hospital
    • Ottawa, Ontario, Canada, K1H8L6
      • Recruiting
      • Ottawa Hospital Research Institute- The Ottawa Hospital
      • Contact: Madeline Hill; Phone Number: 613-737-8899; Email: madhill@ohri.ca
      • Principal Investigator: Marc Carrier, Dr
      • Sub-Investigator: Tzu-Fei Wang, Dr
      • Contact: Amanda Pecarskie; Phone Number: 6137378899; Email: apecarskie@ohri.ca
    • Sault Ste Marie, Ontario, Canada, 750 Great Northern Rd.
      • Recruiting
      • Sault Area Hospital
    • St. Catharines, Ontario, Canada, L2S0A9
      • Recruiting
      • Niagara Health
    • Windsor, Ontario, Canada, N8W 1L9
      • Recruiting
      • Windsor Regional Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Recruiting
      • CISSS Montérégie-Centre HOPITAL CHARLES LEMOYNE
    • Lévis, Quebec, Canada
      • Recruiting
      • Centre integre de sante et de services sociaux de Chaudiere-Appalaches
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
    • Montreal, Quebec, Canada
      • Recruiting
      • McGill University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Rivaroxaban 10mg OD	Drug: Rivaroxaban 10 MG; Identical comparator drug; Other Names: Placebo
Placebo Comparator: Control; Identical Placebo 10mg OD	Drug: Rivaroxaban 10 MG; Identical comparator drug; Other Names: Placebo

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Dr. Marc Carrier, Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Rivaroxaban
• Other Study ID Numbers: TRIM-Line 3698

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No