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

Primary Purpose

Venous Thromboembolism, Cancer

Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Rivaroxaban 10 MG
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Venous Thromboembolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 indication
  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

Sites / Locations

  • HHS - Juravinski HospitalRecruiting
  • Ottawa Hospital Research Institute- The Ottawa HospitalRecruiting
  • Sault Area HospitalRecruiting
  • Niagara HealthRecruiting
  • Windsor Regional HospitalRecruiting
  • CISSS Montérégie-Centre HOPITAL CHARLES LEMOYNERecruiting
  • Jewish General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental

Control

Arm Description

Rivaroxaban 10mg OD

Identical Placebo 10mg OD

Outcomes

Primary Outcome Measures

Major VTE prevention
Number of Major VTE's in patient population
Episodes of Major Bleeding
Number of participants who had a major bleed

Secondary Outcome Measures

Number of participants with Clinically Relevant Non-Major Bleeding (CRNMB)
As defined by ISTH
Number of patients who had a fatal VTE
Fatal VTE
Number of patients who benefitted from using the experimental intervention
Composite of major VTE and major bleeding
PE
Incidental and Symptomatic
Proximal CVC VTE
Incidental and symptomatic proximal (axillary vein or more proximal) upper extremity CVC-related DVT
Distal CVC VTE
Incidental and symptomatic distal (brachial vein) or proximal (axillary vein or more proximal) upper extremity CVC-related DVT
Proximal Lower extremity DVT
Incidental and symptomatic proximal (popliteal vein or more proximal) lower extremity DVT
Distal Lower extremity DVT
Incidental and symptomatic distal or proximal (popliteal vein or more proximal) lower extremity DVT
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
Number of participants with Superficial upper or lower extremity vein thrombosis
Superficial upper or lower extremity vein thrombosis
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
CVC Life-span
Life span of inserted CVC
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.
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
Number of participants who passed away during the trial
Overall mortality
EQ-5D-5L Health-related quality of life
Health-related quality of life
ICER
Incremental cost-effectiveness ratio (ICER) at one year

Full Information

First Posted
June 30, 2021
Last Updated
September 27, 2023
Sponsor
Ottawa Hospital Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05029063
Brief Title
Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters
Acronym
TRIM-Line
Official Title
Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2022 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double Blind Randomized Control Trial
Allocation
Randomized
Enrollment
1828 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Experimental
Arm Description
Rivaroxaban 10mg OD
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Identical Placebo 10mg OD
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 10 MG
Other Intervention Name(s)
Placebo
Intervention Description
Identical comparator drug
Primary Outcome Measure Information:
Title
Major VTE prevention
Description
Number of Major VTE's in patient population
Time Frame
90 days (± 3 days) of randomization
Title
Episodes of Major Bleeding
Description
Number of participants who had a major bleed
Time Frame
90 days (± 3 days) of randomization
Secondary Outcome Measure Information:
Title
Number of participants with Clinically Relevant Non-Major Bleeding (CRNMB)
Description
As defined by ISTH
Time Frame
90 days (± 3 days) of randomization
Title
Number of patients who had a fatal VTE
Description
Fatal VTE
Time Frame
90 days (± 3 days) of randomization
Title
Number of patients who benefitted from using the experimental intervention
Description
Composite of major VTE and major bleeding
Time Frame
90 days (± 3 days) of randomization
Title
PE
Description
Incidental and Symptomatic
Time Frame
90 days (± 3 days) of randomization
Title
Proximal CVC VTE
Description
Incidental and symptomatic proximal (axillary vein or more proximal) upper extremity CVC-related DVT
Time Frame
90 days (± 3 days) of randomization
Title
Distal CVC VTE
Description
Incidental and symptomatic distal (brachial vein) or proximal (axillary vein or more proximal) upper extremity CVC-related DVT
Time Frame
90 days (± 3 days) of randomization
Title
Proximal Lower extremity DVT
Description
Incidental and symptomatic proximal (popliteal vein or more proximal) lower extremity DVT
Time Frame
90 days (± 3 days) of randomization
Title
Distal Lower extremity DVT
Description
Incidental and symptomatic distal or proximal (popliteal vein or more proximal) lower extremity DVT
Time Frame
90 days (± 3 days) of randomization
Title
Number of participants with Unusual site thrombosis including: splanchnic vein (portal, splenic, superior mesenteric, inferior mesenteric, hepatic) cerebral vein, renal or gonadal vein thromboses
Description
Unusual site thrombosis including: splanchnic vein (portal, splenic, superior mesenteric, inferior mesenteric, hepatic) cerebral vein, renal or gonadal vein thromboses
Time Frame
90 days (± 3 days) of randomization
Title
Number of participants with Superficial upper or lower extremity vein thrombosis
Description
Superficial upper or lower extremity vein thrombosis
Time Frame
90 days (± 3 days) of randomization
Title
Number of participants with an arterial thromboembolic event including: MI, stroke, peripheral arterial disease
Description
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
Time Frame
90 days (± 3 days) of randomization
Title
CVC Life-span
Description
Life span of inserted CVC
Time Frame
90 days (± 3 days) of randomization
Title
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.
Description
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.
Time Frame
90 days (± 3 days) of randomization
Title
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
Description
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
Time Frame
90 days (± 3 days) of randomization
Title
Number of participants who passed away during the trial
Description
Overall mortality
Time Frame
90 days (± 3 days) of randomization
Title
EQ-5D-5L Health-related quality of life
Description
Health-related quality of life
Time Frame
90 days (± 3 days) of randomization
Title
ICER
Description
Incremental cost-effectiveness ratio (ICER) at one year
Time Frame
1 Year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Pecarskie
Phone
613-737-8899
Email
apecarskie@ohri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Marc Carrier
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
HHS - Juravinski Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Individual Site Status
Recruiting
Facility Name
Ottawa Hospital Research Institute- The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Pecarskie
Phone
6137378899
Email
apecarskie@ohri.ca
First Name & Middle Initial & Last Name & Degree
Madeline Hill
Phone
613-737-8899
Email
madhill@ohri.ca
First Name & Middle Initial & Last Name & Degree
Marc Carrier, Dr
First Name & Middle Initial & Last Name & Degree
Tzu-Fei Wang, Dr
Facility Name
Sault Area Hospital
City
Sault Ste Marie
State/Province
Ontario
ZIP/Postal Code
750 Great Northern Rd.
Country
Canada
Individual Site Status
Recruiting
Facility Name
Niagara Health
City
St. Catharines
State/Province
Ontario
ZIP/Postal Code
L2S0A9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Windsor Regional Hospital
City
Windsor
State/Province
Ontario
ZIP/Postal Code
N8W 1L9
Country
Canada
Individual Site Status
Recruiting
Facility Name
CISSS Montérégie-Centre HOPITAL CHARLES LEMOYNE
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Individual Site Status
Recruiting
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34027291
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.
Results Reference
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Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters

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