Sickle Cell Disease, Central Venous Catheter Thrombosis, Venous Thromboembolism
Conditions
Brief summary
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.
Interventions
Rivaroxaban 10mg PO daily as thromboprophylaxis
DRUGPlacebo
matching placebo daily
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult (age 18 or older) 2. Documented SCD 3. New or pre-existing CVC planned for long term use (at least 6 months) 4. Able to provide written consent
Exclusion criteria
1. Contra-indication to prophylactic dose anticoagulation or active bleeding at discretion of treating physician 2. Already on anticoagulation (prophylactic or therapeutic dose) for an indication other than CVC thromboprophylaxis 3. Previous VTE within the past 3 months 4. Pregnant, within 6 weeks post-partum, or active breast feeding 5. Creatinine clearance \<30mL/min (as calculated by Cockcroft-Gault equation\[67\]) 6. Acute hepatitis or chronic active hepatitis 7. Cirrhosis with Child-Pugh score B or C 8. Platelet count \< 50 x109/L 9. Weight \<40kg 10. Uncontrolled HTN (systolic blood pressure \> 170mmhg, or diastolic blood pressure\> 100mmhg) despite antihypertensive treatment 11. On palliative care 12. On dual antiplatelet therapy, or high dose single agent aspirin \> 325mg/day 13. On combined P-glycoprotein and strong cytochrome P450 3A4 inhibitors (including but not limited to ketoconazole and protease inhibitors) 14. On combined P-glycoprotein and strong cytochrome P450 3A4 inducers (including but not limited to rifampin, phenytoin, phenobarbital, carbamazepine, and st. john's wort) 15. Active cancer or treatment for cancer excluding basal cell carcinoma 16. Known allergy to study drug 17. Strong indication for thromboprophylaxis at discretion of treating physician 18. Significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of eligible patients who will enroll into a trial of thromboprophylaxis | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 1 year | 1. Adherence: percentage of administered drugs not returned (by pill counting); 2. Compliance: defined as percentage adherence \>80%. |
| Estimate participants compliance with study procedures, and lost to follow up | 1 year | Defined as proportion of participant lost to follow up or withdrawn from the study prior to completion of 6 months of treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinically relevant non-major bleeding | 1 year | Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria |
| CVC change due to thrombosis or catheter occlusion not amenable to infusion of thrombolytics between study arms | 1 year | Proportion of participants requiring CVC change due to thrombosis or catheter occlusion not amenable to infusion of thrombolytics |
| Event-free survival | 1 year | Defined as free from VTE or major bleeding events |
| Bruising using a Likert scale | 1 year | A one item survey with the question Over the past 3 months, have you noticed any abnormal bruising? with response ranging from 0 (no bruising) to 10 (lots of bruising). |
| Quality of life using the modified Duke Anticoagulation Satisfaction Scale | 1 year | The modified Duke Anticoagulation Satisfaction Scale is a 14 item scale addressing the negative and positive impacts of anticoagulation with participants rating items as strongly agree, agree, neither agree nor disagree, disagree, or strongly disagree |
| Arterial thrombotic events | 1 year | Including myocardial infarction, ischemic stroke, and systemic embolism |
| Venous thromboembolism (VTE) | 1 year | Proportion of participants with VTE (including CRT, right atrial or ventricular thrombus, proximal DVT, segmental PE, unusual site VTE), and unexplained death in which PE could not be ruled out. CRT is defined to include a proximal vein and must be the same limb as the CVC. Proximal veins include both lower and upper limb, and must include the popliteal or more proximal vein if lower limb, or axillary or more proximal. Unusual site VTE is defined to include cerebral vein thrombosis or splanchnic vein thrombosis. VTE must be objectively confirmed with appropriate imaging modalities. |
| Major bleeding or clinically relevant non-major bleeding | 1 year | Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria |
| Major bleeding | 1 year | Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria |
Countries
Canada
Outcome results
None listed