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

Sickle Cell Disease Clinical Trial

— THIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05033314
• Other study ID #: 20-5846.0
• Status: Recruiting
• Phase: Phase 3
• Start date: June 7, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: September 2023
• Source: University Health Network, Toronto
• Contact: Briana Layard
• Phone: 437-929-5158
• Email: rbcd.clinicaltrials[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Central Venous Catheter Thrombosis
• Sickle Cell Disease
• Thromboembolism
• Thrombosis
• Upper Extremity Deep Vein Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• Rivaroxaban 10 MG
Rivaroxaban 10mg PO daily as thromboprophylaxis
• Placebo
matching placebo daily

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Center	London	Ontario
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Kevin H.M. Kuo, MD, MSc, FRCPC

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Venous thromboembolism (VTE)	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.	1 year
Other	Major bleeding or clinically relevant non-major bleeding	Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria	1 year
Other	Major bleeding	Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria	1 year
Other	Clinically relevant non-major bleeding	Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria	1 year
Other	Event-free survival	Defined as free from VTE or major bleeding events	1 year
Other	Arterial thrombotic events	Including myocardial infarction, ischemic stroke, and systemic embolism	1 year
Other	CVC change due to thrombosis or catheter occlusion not amenable to infusion of thrombolytics between study arms	Proportion of participants requiring CVC change due to thrombosis or catheter occlusion not amenable to infusion of thrombolytics	1 year
Other	Quality of life using the modified Duke Anticoagulation Satisfaction Scale	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"	1 year
Other	Bruising using a Likert scale	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).	1 year
Primary	The proportion of eligible patients who will enroll into a trial of thromboprophylaxis		1 year
Secondary	Document indications for central venous catheter (CVC)		1 year
Secondary	Summarize duration of CVC insertion prior to enrollment		1 year
Secondary	Estimate adherence to the study drug	Adherence: percentage of administered drugs not returned (by pill counting); Compliance: defined as percentage adherence >80%.	1 year
Secondary	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