Thromboprophylaxis With Rivaroxaban In Patients With Malignancy and Central Venous Lines

Phase 3

Completed

Conditions: Central Venous Catheter Thrombosis
Upper Extremity Deep Vein Thrombosis
Cancer

Brief Summary: 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.

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.

Recruitment & Eligibility

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

CVC in place for >72 hours
Patient requires anticoagulation for other indication
Concomitant use of dual antiplatelet therapy
Prior VTE
Major bleeding event in the last 6 weeks
Patient on concomitant medication with known interaction with rivaroxaban (eg. CYP3A4 inhibitor)
Pregnancy (documentation of use of effective contraception if sexually active or negative B-Hcg required)
Known renal failure, based on Creatinine clearance <30 mL/min (Cockcroft-Gault) (in the previous 3 months)
Documented severe liver disease (eg. acute clinical hepatitis, chronic active hepatitis, cirrhosis or ALT >3ULN) ( in the previous 3 months)
Known thrombocytopenia < 50x 109/L (in the previous 3 months)
Allergy to rivaroxaban
Life expectancy <6 months
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
Primary malignancy diagnosis of basal cell or squamous cell carcinoma of the skin or acute leukemia or myelodysplastic syndrome
Geographic inaccessibility
Refused or unable to obtain consent

Arm && Interventions

Group	Intervention	Description
Rivaroxaban Thromboprophylaxis	Rivaroxaban 10 MG	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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