Thromboprophylaxis With Rivaroxaban In Patients With Malignancy and Central Venous Lines (TRIM-Line)

A Pilot Study Assessing the Feasibility of a Randomized Controlled Trial Investigating Primary Thromboprophylaxis With Rivaroxaban in Patients With Malignancy and Central Venous Catheters

Purpose of the Pilot Trial:

To determine the feasibility of conducting a multicentre randomized open label controlled trial evaluating the use of prophylactic dose rivaroxaban to prevent central venous catheter (CVC) associated venous thromboembolism (VTE) among cancer patients.

Hypothesis: treatment with low dose rivaroxaban (10mg) will reduce the incidence of upper extremity venous thrombosis in a high risk population with cancer and CVC.

Study Overview

• Status: Completed
• Conditions: Cancer; Central Venous Catheter Thrombosis; Upper Extremity Deep Vein Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban 10 MG

Detailed Description

Design:

This is a pilot interventional study to be conducted at 2 Canadian Centres. The Ottawa Hospital and Juravinski Hospital. It is an open label randomized controlled trial.

Consenting participants, meeting eligibility criteria will be randomized at the time of enrollment to one of two groups.

Rivaroxaban 10mg by mouth daily x 90 (+/- 3) days OR Standard of Care

Participants in the treatment arm will have study drug dispensed at Day 1 and take medication for 90 days or until CVC is removed. Follow up visits (in person or phone) will occur at Day 30 (+/- 3 days) and Day 90 (+/- 3 days). Overall, participants will be followed for 3 months. Adverse events will be collected for the first 90 days.

Outcomes The primary feasibility outcome for the pilot study is the number of participants recruited per centre per month. We will obtain baseline details of the patient's type, location and treatment of cancer, comorbidities and medications. Secondary feasibility outcomes of the pilot study will include, consent rates, loss to follow up, adherence to therapy defining 80% or greater medication taken as having good adherence to study drug, proportion of screened patients who meet eligibility criteria.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital General Campus

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1.Patients 18 years of age or older with a new or existing diagnosis of cancer with a CVC inserted within 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. Prior VTE
5. Major bleeding event in the last 6 weeks
6. Patient on concomitant medication with known interaction with rivaroxaban (eg. CYP3A4 inhibitor)
7. Pregnancy (documentation of use of effective contraception if sexually active or negative B-Hcg required)
8. Known renal failure, based on Creatinine clearance <30 mL/min (Cockcroft-Gault) (in the previous 3 months)
9. Documented severe liver disease (eg. acute clinical hepatitis, chronic active hepatitis, cirrhosis or ALT >3ULN) ( in the previous 3 months)
10. Known thrombocytopenia < 50x 109/L (in the previous 3 months)
11. Allergy to rivaroxaban
12. Life expectancy <6 months

13. History of condition at increased bleeding risk including, but not limited to:

    1. Major surgical procedure or trauma within 30 days before the randomization visit
    2. Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
    3. History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
    4. Chronic hemorrhagic disorder
    5. Known intracranial neoplasm, arteriovenous malformation, or aneurysm
    6. Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg
14. Primary malignancy diagnosis of basal cell or squamous cell carcinoma of the skin or acute leukemia or myelodysplastic syndrome
15. Geographic inaccessibility
16. 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban Thromboprophylaxis; Rivaroxaban 10 mg po daily for 90 days(+/- 3 days). After the Day - 90 follow up, the study treatment will be discontinued and subsequent treatment will be at the discretion of the attending physician.	Drug: Rivaroxaban 10 MG; Rivaroxaban 10mg po daily x 90 (+/- 3 days); Other Names: Xarelto 10mg tablet po daily
No Intervention: Standard of care; No rivaroxaban prophylaxis. Management will be at the discretion of the attending physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Feasibility Outcome - Number of Participants Recruited Per Month	A convenience sample size of 100 patients was chosen to allow reporting of the average monthly recruitment.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Feasibility Outcomes - Percentage of Participants With Good Adherence to Therapy	Good adherence defined as 80% or greater study medication taken in patients randomized to receive Rivaroxaban thromboprophylaxis.	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Thrombotic Complication	Thrombotic complication was defined as a combination of major venous thromboembolism (VTE); any symptomatic or incidentally detected proximal deep vein thrombosis (DVT) of the lower or upper limbs, any nonfatal symptomatic or incidental pulmonary embolism (PE), and pulmonary embolism-related death) and any other deep (ie, distal, splanchnic, or cerebral) or superficial venous thrombosis.	90 days
Number of Participants With CVC-Related Complication	Central venous catheter (CVC) occlusion was 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
Number of Participants With Major Bleeding	Defined by the International Society on Thrombosis and Haemostasis (ISTH) as overt bleeding associated with a decrease in the hemoglobin level of ≥2 g/dL, which led to transfusion of two or more units of packed red blood cells, occurred in a critical site, or contributed to death.	90 days
Number of Participants With Clinically Relevant Non-Major Bleed	Clinically relevant non-major bleeding, as per the standardized definition by the ISTH, is any signs or symptoms of hemorrhage not meeting criteria for major bleeding but associated with medical intervention, unscheduled in-person contact with a healthcare professional or need for hospitalization or increased level of care.	90 days

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: University of Alberta; Hamilton Health Sciences Corporation; Queen Elizabeth II Health Sciences Centre
• Investigators: Principal Investigator: Rick T Ikesaka, MD, Ottawa Hospital Research Institute / Division of Hematology- The Ottawa Hospital

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): March 15, 2019
• Primary Completion (Actual): May 14, 2020
• Study Completion (Actual): June 14, 2020

Study Registration Dates

• First Submitted: March 19, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Thromboprophylaxis; Randomized Trial; Upper Extremity Deep Vein Thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Upper Extremity Deep Vein Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 001 (Buy Pharma Ecza Deposu San. Tic. Ltd.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pilot Feasibility Study- no current plan to share individual participant data

Drug and device information, study documents

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