THromboprophylaxis In Sickle Cell Disease With Central Venous Catheters (THIS)

Study Overview
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Brief Summary
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Research Question: In adult SCD patients with CVC, is it feasible and safe to conduct an adequately powered RCT to evaluate the use of rivaroxaban as thromboprophylaxis in this population? Study Design: The study is a vanguard pilot double blind multi-centre randomized controlled trial. Participants with SCD and CVC will be randomized to either rivaroxaban 10mg PO daily or placebo for the duration of CVC in situ or for up to one year, whichever is less. After screening (day -7 to day -1), patients will be followed at day 1, months 3 (+/- 15 days), 6 (+/- 15 days), 9 (+/- 15 days), and 12 (+/- 15 days). Study Objectives: The primary objective is to estimate the proportion of eligible patients who will enroll into a trial of thromboprophylaxis. Secondary objectives include (a) document indications for central venous catheter (CVC), (b) summarize duration of CVC insertion prior to enrollment, (c) estimate adherence to the study drug, (d) estimate proportions of participants being compliant with study procedures, and lost to follow up. Exploratory objectives will assess thrombotic, bleeding, and quality of life outcomes.

Official Title
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THromboprophylaxis In Sickle Cell Disease With Central Venous Catheters (THIS): A Pilot Study

Conditions
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Sickle Cell Disease, Central Venous Catheter Thrombosis, Venous Thromboembolism

Intervention / Treatment
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* Drug: Rivaroxaban 10 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (age 18 or older) Documented SCD New or pre-existing CVC planned for long term use (at least 6 months) Able to provide written consent Exclusion Criteria: Contra-indication to prophylactic dose anticoagulation or active bleeding at discretion of treating physician Already on anticoagulation (prophylactic or therapeutic dose) for an indication other than CVC thromboprophylaxis Previous VTE within the past 3 months Pregnant, within 6 weeks post-partum, or active breast feeding Creatinine clearance <30mL/min (as calculated by Cockcroft-Gault equation[67]) Acute hepatitis or chronic active hepatitis Cirrhosis with Child-Pugh score B or C Platelet count < 50 x109/L Weight <40kg Uncontrolled HTN (systolic blood pressure > 170mmhg, or diastolic blood pressure> 100mmhg) despite antihypertensive treatment On palliative care On dual antiplatelet therapy, or high dose single agent aspirin > 325mg/day On combined P-glycoprotein and strong cytochrome P450 3A4 inhibitors (including but not limited to ketoconazole and protease inhibitors) On combined P-glycoprotein and strong cytochrome P450 3A4 inducers (including but not limited to rifampin, phenytoin, phenobarbital, carbamazepine, and st. john's wort) Active cancer or treatment for cancer excluding basal cell carcinoma Known allergy to study drug Strong indication for thromboprophylaxis at discretion of treating physician Significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban thromboprophylaxis<br> | Drug: Rivaroxaban 10 MG<br>* Rivaroxaban 10mg PO daily as thromboprophylaxis<br>* Other names: Xarelto 10mg;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* matching placebo daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of eligible patients who will enroll into a trial of thromboprophylaxis |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Document indications for central venous catheter (CVC) |  | 1 year | 
| Summarize duration of CVC insertion prior to enrollment |  | 1 year | 
| Estimate adherence to the study drug | Adherence: percentage of administered drugs not returned (by pill counting); Compliance: defined as percentage adherence >80%. | 1 year | 
| Estimate participants compliance with study procedures, and lost to follow up | Defined as proportion of participant lost to follow up or withdrawn from the study prior to completion of 6 months of treatment | 1 year |