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 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.

Design:

This is a pilot interventional study to be conducted at 3 Canadian Centres. The Ottawa Hospital, QEII Health Science Centre and University of Alberta 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 po 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. Follow up visits (in person or phone) will occur at Day 30 (+/- 3 days) and Day 90 (+/- 3 days) month and 3 months post enrollment. 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 Overview

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

• Study Type: Interventional
• Enrollment (Actual): 100
• 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
• Genders Eligible for Study: All

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
• Masking: NONE

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
Pilot Feasibility Outcome- Enrolment	Number of Participants recruited per centre per month	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consent rate	Proportion of approached patients who consent to enter study.	6 months
Loss to follow up	During the 90 (+/-3) days of the trial	6 months
Adherence to Therapy	Good adherence defined as 80% or greater study medication taken	6 months
Proportion of screened patients which meet eligibility criteria		6 months

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 23, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2020

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 (NavyGHB)

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 IPD

Drug and device information, study documents

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