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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Venous Thromboembolism; Central Venous Catheter Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban 10 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Briana Layard; Phone Number: 437-929-5158; Email: rbcd.clinicaltrials@uhn.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • University of Alberta Hospital
      • Principal Investigator: Linda Sun, MD, MSc
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Center
      • Principal Investigator: Ziad Solh, MD, MSc
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital
      • Principal Investigator: Jameel Abdulrehman, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; matching placebo daily
Experimental: Rivaroxaban thromboprophylaxis	Drug: Rivaroxaban 10 MG; Rivaroxaban 10mg PO daily as thromboprophylaxis; Other Names: Xarelto 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Major bleeding or clinically relevant non-major bleeding	Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria	1 year
Major bleeding	Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria	1 year
Clinically relevant non-major bleeding	Defined as per International Society on Thrombosis and Haemostasis (ISTH) criteria	1 year
Event-free survival	Defined as free from VTE or major bleeding events	1 year
Arterial thrombotic events	Including myocardial infarction, ischemic stroke, and systemic embolism	1 year
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
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
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

Collaborators and Investigators

• Sponsor: Kevin H.M. Kuo, MD, MSc, FRCPC

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 5, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 30, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Embolism and Thrombosis; Anemia; Venous Thrombosis; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thrombosis; Anemia, Sickle Cell; Thromboembolism; Venous Thromboembolism; Upper Extremity Deep Vein Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 20-5846.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study data will be disclosed after successful conclusion of the definitive phase 3 study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No