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Rivaroxaban in Thrombotic Antiphospholipid Syndrome (TRAPS)

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ClinicalTrials.gov Identifier: NCT02157272
Recruitment Status : Terminated (Unbalance in the composite endpoint between arms.)
First Posted : June 5, 2014
Last Update Posted : January 30, 2018
Sponsor:
Information provided by (Responsible Party):
Vittorio Pengo, University of Padova

Tracking Information
First Submitted Date  ICMJE May 31, 2014
First Posted Date  ICMJE June 5, 2014
Last Update Posted Date January 30, 2018
Study Start Date  ICMJE December 2014
Actual Primary Completion Date January 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2014)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2014)
  • • Any single type of thromboembolic event [ Time Frame: up to 4 years ]
  • All-cause mortality [ Time Frame: up to 4 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rivaroxaban in Thrombotic Antiphospholipid Syndrome
Official Title  ICMJE A Prospective, Randomized Clinical Trial Comparing Rivaroxaban vs Warfarin in High Risk Patients With Antiphospholipid Syndrome
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Antiphospholipid Syndrome
Intervention  ICMJE Drug: Experimental: Rivaroxaban
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.
Other Name: Xarelto
Study Arms  ICMJE
  • Experimental: Rivaroxaban
    Rivaroxaban 20mg qd, Rivaroxaban 15mg qd if creatinine clearance between 30-49 ml/min (calculated by Cockroft-Gault equation)
    Intervention: Drug: Experimental: Rivaroxaban
  • Active Comparator: Warfarin
    To Keep an INR between 2.0 and 3.0
    Intervention: Drug: Experimental: Rivaroxaban
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 27, 2018)
121
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2014)
536
Actual Study Completion Date  ICMJE January 25, 2018
Actual Primary Completion Date January 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed and dated informed consent form
  2. Male or female of age 18-75 years
  3. 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.
  4. 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:

  1. Severe hypersensitivity reaction to rivaroxaban
  2. Calculated CLCR <30 mL/min at the screening visit
  3. 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
  4. 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.
  5. 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.
  6. 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
  7. Known liver cirrhosis or ALT above three times the upper normal value.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02157272
Other Study ID Numbers  ICMJE EUDRACT 2013-004575-13
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vittorio Pengo, University of Padova
Study Sponsor  ICMJE University of Padova
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Padova
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP