Rivaroxaban in Thrombotic Antiphospholipid Syndrome (TRAPS)
Primary Purpose
Antiphospholipid Syndrome
Status
Terminated
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Experimental: Rivaroxaban
Sponsored by
About this trial
This is an interventional treatment trial for Antiphospholipid Syndrome focused on measuring Antiphospholipid, Syndrome, Rivaroxaban, Warfarin, Thrombosis, Treatment
Eligibility Criteria
Inclusion Criteria:
- Signed and dated informed consent form
- Male or female of age 18-75 years
Triple aPL-positivity in the last blood sampling defined as:
- aCL IgG/M (≥40 GPL or MPL, medium-to-high titer, and/or greater than the 99th percentile) and
- aB2GPI IgG/M (≥40 U, medium-to-high titer, and/or greater than the 99th percentile) and
- LA test positive based on the International Society of Thrombosis & Hemostasis Recommendations.
- Positivity of aCL and abeta2GPI must be of the same isotype.
- To confirm triple positivity for aPL and to validate the laboratory diagnosis, plasma (at least 2ml prepared by double centrifugation at 2000g) from patients of each Center will be stored at -80°C and later on sent in dry ice and retested in a reference laboratory (Padua Thrombosis Centre). Expenses for shipment will be in charge to the coordinator Center.
- History of thrombosis (objectively proven arterial, venous, and/or biopsy proven microthrombosis) and/or pregnancy morbidity according to Miyaki
Exclusion Criteria:
Subjects meeting any of the following criteria will not be enrolled in the study:
- Severe hypersensitivity reaction to rivaroxaban
- Calculated CLCR <30 mL/min at the screening visit
- Current pregnancy or breast feeding. Pregnancy is highly discouraged in these patients and if programmed patients are excluded from the study. If sexually active, be practicing an effective method of birth control (e.g., intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study
- Concomitant treatment with other anticoagulants, such as unfractionated heparin, low molecular weight heparins (enoxaparin, dalteparin, etc.) heparin derivatives (fondaparinux), other oral anticoagulants (dabigatran etexilate, apixaban) in the case they can not be substituted with the study drugs.
- Patients taking interfering medications: pharmacologic interactions may occur with strong inhibitors of p-glycoprotein and of CYP3A4, e.g., azole-antimycotics, such as ketoconazole, itraconazole, voriconazole, posaconazole, and HIV protease inhibitors; coadministration of rivaroxaban is therefore contraindicated in these cases. Several drugs used in neurological patients, such as phenobarbital, phenytoin, carbamazepine, and st john's wort (hypericum), are p-glycoprotein inducers and should be avoided. Whenever possible, it would be better to use levetiracetam and topiramate as antiepileptic therapy.
Hemorrhage Risk-Related Criteria
- History of or condition associated with increased bleeding risk including, but not limited to:
- Major surgical procedure or trauma within 30 days before the randomization visit
- Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
- History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
- Chronic hemorrhagic disorder
- Known intracranial neoplasm, arteriovenous malformation, or aneurysm
- Planned invasive procedure with potential for uncontrolled bleeding.
- Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg
- Known liver cirrhosis or ALT above three times the upper normal value.
Sites / Locations
- University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Rivaroxaban
Warfarin
Arm Description
Rivaroxaban 20mg qd, Rivaroxaban 15mg qd if creatinine clearance between 30-49 ml/min (calculated by Cockroft-Gault equation)
To Keep an INR between 2.0 and 3.0
Outcomes
Primary Outcome Measures
Cumulative outcome measure will be incident acute thrombosis (arterial or venous) confirmed by appropriate imaging studies, major bleeding, or death.
Secondary Outcome Measures
• Any single type of thromboembolic event
All-cause mortality
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02157272
Brief Title
Rivaroxaban in Thrombotic Antiphospholipid Syndrome
Acronym
TRAPS
Official Title
A Prospective, Randomized Clinical Trial Comparing Rivaroxaban vs Warfarin in High Risk Patients With Antiphospholipid Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
Unbalance in the composite endpoint between arms.
Study Start Date
December 2014 (undefined)
Primary Completion Date
January 25, 2018 (Actual)
Study Completion Date
January 25, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Padova
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary Study Objective(s) The primary objective is to demonstrate the non-inferiority of Rivaroxaban 20 mg (or 15mgqd in case of moderate renal insufficiency) versus warfarin (INR 2.0-3.0) with respect to the occurrence of the cumulative end point of incident acute thrombosis (arterial or venous) confirmed by appropriate imaging studies, major bleedings, and death in triple aPL-positive APS patients.
Study Design A multicentre, interventional, prospective, parallel, randomised, controlled, open-label, Rivaroxaban 20 mg qd (or 15mg qd in patients with moderate renal insufficiency) vs warfarin (INR target 2.5), non-inferiority study, in 535 triple aPL-positive APS patients in approximately 40 Internal Medicine and Thrombosis centres. Each local Institutional Review Board will approve the study.
Study Population Patients of both sexes, of age 18-75, affected by anti-phospholipid syndrome, with a high probability of recurrences as defined by triple aPL-positivity, are eligible for this study.
Primary Outcome variables The primary cumulative outcome measure will be incident acute thrombosis (arterial or venous) confirmed by appropriate imaging studies, major bleeding, or death.
Secondary Outcome variables Separate evaluation of arterial and venous thrombosis and all-cause death.
04.27.2015: An amendment has been made. Enrollment permitted till 75 years of age.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antiphospholipid Syndrome
Keywords
Antiphospholipid, Syndrome, Rivaroxaban, Warfarin, Thrombosis, Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
121 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rivaroxaban
Arm Type
Experimental
Arm Description
Rivaroxaban 20mg qd, Rivaroxaban 15mg qd if creatinine clearance between 30-49 ml/min (calculated by Cockroft-Gault equation)
Arm Title
Warfarin
Arm Type
Active Comparator
Arm Description
To Keep an INR between 2.0 and 3.0
Intervention Type
Drug
Intervention Name(s)
Experimental: Rivaroxaban
Other Intervention Name(s)
Xarelto
Intervention Description
The investigated drug is Rivaroxaban 20mg, a film coated tablet, which is a highly selective direct factor Xa inhibitor. It should be administered orally, every day at any time (always the same), with food. The treatment should be performed for all the treatment period.
Primary Outcome Measure Information:
Title
Cumulative outcome measure will be incident acute thrombosis (arterial or venous) confirmed by appropriate imaging studies, major bleeding, or death.
Time Frame
up to 4 years
Secondary Outcome Measure Information:
Title
• Any single type of thromboembolic event
Time Frame
up to 4 years
Title
All-cause mortality
Time Frame
up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed and dated informed consent form
Male or female of age 18-75 years
Triple aPL-positivity in the last blood sampling defined as:
aCL IgG/M (≥40 GPL or MPL, medium-to-high titer, and/or greater than the 99th percentile) and
aB2GPI IgG/M (≥40 U, medium-to-high titer, and/or greater than the 99th percentile) and
LA test positive based on the International Society of Thrombosis & Hemostasis Recommendations.
Positivity of aCL and abeta2GPI must be of the same isotype.
To confirm triple positivity for aPL and to validate the laboratory diagnosis, plasma (at least 2ml prepared by double centrifugation at 2000g) from patients of each Center will be stored at -80°C and later on sent in dry ice and retested in a reference laboratory (Padua Thrombosis Centre). Expenses for shipment will be in charge to the coordinator Center.
History of thrombosis (objectively proven arterial, venous, and/or biopsy proven microthrombosis) and/or pregnancy morbidity according to Miyaki
Exclusion Criteria:
Subjects meeting any of the following criteria will not be enrolled in the study:
Severe hypersensitivity reaction to rivaroxaban
Calculated CLCR <30 mL/min at the screening visit
Current pregnancy or breast feeding. Pregnancy is highly discouraged in these patients and if programmed patients are excluded from the study. If sexually active, be practicing an effective method of birth control (e.g., intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study
Concomitant treatment with other anticoagulants, such as unfractionated heparin, low molecular weight heparins (enoxaparin, dalteparin, etc.) heparin derivatives (fondaparinux), other oral anticoagulants (dabigatran etexilate, apixaban) in the case they can not be substituted with the study drugs.
Patients taking interfering medications: pharmacologic interactions may occur with strong inhibitors of p-glycoprotein and of CYP3A4, e.g., azole-antimycotics, such as ketoconazole, itraconazole, voriconazole, posaconazole, and HIV protease inhibitors; coadministration of rivaroxaban is therefore contraindicated in these cases. Several drugs used in neurological patients, such as phenobarbital, phenytoin, carbamazepine, and st john's wort (hypericum), are p-glycoprotein inducers and should be avoided. Whenever possible, it would be better to use levetiracetam and topiramate as antiepileptic therapy.
Hemorrhage Risk-Related Criteria
History of or condition associated with increased bleeding risk including, but not limited to:
Major surgical procedure or trauma within 30 days before the randomization visit
Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
Chronic hemorrhagic disorder
Known intracranial neoplasm, arteriovenous malformation, or aneurysm
Planned invasive procedure with potential for uncontrolled bleeding.
Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg
Known liver cirrhosis or ALT above three times the upper normal value.
Facility Information:
Facility Name
University Hospital
City
Padova
ZIP/Postal Code
35128
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
30002145
Citation
Pengo V, Denas G, Zoppellaro G, Jose SP, Hoxha A, Ruffatti A, Andreoli L, Tincani A, Cenci C, Prisco D, Fierro T, Gresele P, Cafolla A, De Micheli V, Ghirarduzzi A, Tosetto A, Falanga A, Martinelli I, Testa S, Barcellona D, Gerosa M, Banzato A. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018 Sep 27;132(13):1365-1371. doi: 10.1182/blood-2018-04-848333. Epub 2018 Jul 12.
Results Reference
derived
Links:
URL
http://www.dctv.unipd.it
Description
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Rivaroxaban in Thrombotic Antiphospholipid Syndrome
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