Clinical trial NCT05033314: THromboprophylaxis In Sickle Cell Disease With Central Venous Catheters (THIS)
Official title: THromboprophylaxis In Sickle Cell Disease With Central Venous Catheters (THIS): A Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Sickle Cell Disease
Central Venous Catheter Thrombosis
Venous Thromboembolism
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2021-09-02
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of eligible patients who will enroll into a trial of thromboprophylaxis
timeFrame: 1 year
Secondary outcomes:
measure: Document indications for central venous catheter (CVC)
timeFrame: 1 year
measure: Summarize duration of CVC insertion prior to enrollment
timeFrame: 1 year
measure: Estimate adherence to the study drug
timeFrame: 1 year
measure: Estimate participants compliance with study procedures, and lost to follow up
timeFrame: 1 year
Other outcomes:
measure: Venous thromboembolism (VTE)
timeFrame: 1 year
measure: Major bleeding or clinically relevant non-major bleeding
timeFrame: 1 year
measure: Major bleeding
timeFrame: 1 year
measure: Clinically relevant non-major bleeding
timeFrame: 1 year
measure: Event-free survival
timeFrame: 1 year
measure: Arterial thrombotic events
timeFrame: 1 year
measure: CVC change due to thrombosis or catheter occlusion not amenable to infusion of thrombolytics between study arms
timeFrame: 1 year
measure: Quality of life using the modified Duke Anticoagulation Satisfaction Scale
timeFrame: 1 year
measure: Bruising using a Likert scale
timeFrame: 1 year
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
References: