Rivaroxaban for Antiphospholipid Antibody Syndrome (RAPS)

Rivaroxaban in Antiphospholipid Syndrome Pilot Study: A Multicenter Feasibility Study of Rivaroxaban for Patients With Antiphospholipid Syndrome and Prior Arterial or Venous Thrombosis

The antiphospholipid antibody syndrome (APS) is a syndrome associated with excessive blood clotting (thrombosis). APS is among the most common cause of heart attack and stroke in patients under the age of 50 and is particularly prevalent in patients with autoimmune conditions. Patients with APS and prior thrombosis require lifelong anticoagulant therapy to prevent recurrent clots; such therapy is currently provided with warfarin. Warfarin requires frequent bloodwork monitoring, and many medications or foods can alter its effect, which can put people either at increased risk for clotting or bleeding. Rivaroxaban is a new mediation that prevents blood clots that does not require bloodwork monitoring and that has fewer interactions. This study is a pilot feasibility study which will: 1) examine our ability to identify 150 eligible APS patients; 2) measure our ability to obtain consent from 135 of these patients; and 3) test our hypothesis that we can obtain 95% compliance with daily rivaroxaban administration. The investigators propose to treat eligible patients with rivaroxaban 20 mg once daily. Patients will be followed for a minimum of one year and their rates of bleeding and thrombosis will be monitored as secondary outcome measures.

Study Overview

• Status: Completed
• Conditions: Antiphospholipid Antibody Syndrome
• Intervention / Treatment: Drug: Rivaroxaban

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2P4
      • University of Alberta Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Prior objectively-confirmed venous thrombosis, irrespective of history of arterial thrombosis
• Two or more prior positive APS serological evaluations at least 12 weeks apart
• Current treatment with warfarin administered to achieve an INR of 2.0 to 3.0, rivaroxaban or dabigatran at any dose currently used for secondary prophylaxis of thrombosis, or short term therapeutic dose LMWH (for example, for the treatment of recently diagnosed deep vein thrombosis). Patients not currently receiving anticoagulation but in whom anticoagulation is mandated, may also be enrolled if a 20 mg rivaroxaban dose would be appropriate

Exclusion Criteria:

• Prior recurrent thrombosis while taking warfarin with a demonstrated INR of 2.0 to 3.0, or prior recurrent thrombosis while receiving dabigatran or rivaroxaban
• History of isolated arterial thrombosis (no history of venous thrombosis) pending CTA approval by Health Canada
• Need for continued treatment with both aspirin (irrespective of dose) AND clopidogrel
• Pregnancy or planned pregnancy during the study period; women who may become pregnant will be required to utilize reliable contraceptive measures while on study drug
• Chronic kidney disease with calculated GFR < 30mL/min
• Geographic inaccessibility
• Age < 18 years
• Inability or failure to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Rivaroxaban 20mg po daily	Drug: Rivaroxaban; Other Names: Xarelto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of identification for enrolment	The investigators define success as the ability to identify 150 eligible patients at 6 clinical centres over 18 months.	18 months
Feasibility of Consent	The investigators define success as a consent rate of 90% (thus, if we identify 150 patients, at least 135 will provide consent).	18 months
Compliance	The investigators define success as a patient missing fewer than 5% of days with pill administrations, as measured by pill counts.	Minimum of one year for all subjects

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding	The investigators will collect and report the rates of minor bleeding (clinically apparent bleeding that does not meet the criteria for major), and major and fatal bleeding. Major bleeding will be defined by International Society of Thrombosis and Hemostasis criteria.	Minimum of one year for all subjects
Thrombosis	The investigators will collect and report the rates of objectively-confirmed venous and arterial thrombosis.	Minimum of one year for all subjects

Collaborators and Investigators

• Sponsor: St. Joseph's Healthcare Hamilton
• Collaborators: Bayer; University of Alberta; The Ottawa Hospital; Hamilton Health Sciences Corporation; Jewish General Hospital; Heart and Stroke Foundation of Canada; Queen Elizabeth II Health Sciences Centre
• Investigators: Principal Investigator: Kimberly J Legault, MD, St. Joseph's Healthcare Hamilton, Hamilton Health Sciences; Principal Investigator: Mark A Crowther, MD, MSc, St. Joseph's Healthcare Hamilton

Publications and helpful links

General Publications

• Legault K, Blostein M, Carrier M, Khan S, Schulman S, Shivakumar S, Wu C, Crowther MA. A single-arm feasibility cohort study of rivaroxaban in antiphospholipid syndrome. Pilot Feasibility Stud. 2020 Apr 25;6:52. doi: 10.1186/s40814-020-00594-1. eCollection 2020. Erratum In: Pilot Feasibility Stud. 2020 May 18;6:67.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): September 30, 2017
• Study Completion (Actual): September 30, 2017

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 14, 2014
• First Posted (Estimate): April 16, 2014

Study Record Updates

• Last Update Posted (Actual): October 18, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Feasibility; Rivaroxaban; Bleeding; Thromboembolism; Antiphospholipid Antibody Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease; Syndrome; Antiphospholipid Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: G-13-0002011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided