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Completed

NCT Number: NCT03178864

Study of Rivaroxaban for CeREbral Venous Thrombosis

SECRET examines the safety of rivaroxaban versus standard-of-care for treatment of symptomatic cerebral venous thrombosis, initiated within 14 days of diagnosis.

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Key information

Conditions

Cerebral Venous Thrombosis Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Embolism and Thrombosis Intracranial Embolism and Thrombosis Intracranial Thrombosis Nervous System Diseases Thromboembolism Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Foothills Medical Centre, Calgary, Alberta, Canada

Loading trial locations.

About this study

SECRET is an open-label, randomized, controlled, phase II study that will assess the safety of rivaroxaban, a non-vitamin K antagonist oral anticoagulant (NOAC), compared with standard-of-care (unfractionated or low-molecular weight heparin with transition to warfarin [INR 2.0-3.0], or continued low molecular-weight heparin) for cerebral venous thrombosis. Recruitment will occur at 17 high-volume stroke research centres across Canada over 3 years. During the pilot phase, 50 adult patients within 14 days of symptomatic cerebral venous thrombosis diagnosis will be randomized to receive rivaroxaban 20 mg daily versus standard of care (warfarin or low-molecular weight heparin). Patients will be followed for 1 year. The feasibility of recruitment will be tested during the pilot phase and outcomes refined for a future Phase III trial.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients aged 18 and above
  • New diagnosis of symptomatic cerebral venous thrombosis as confirmed on CT venogram or MR venogram
  • Ability to randomize within 14 days of neuroimaging-confirmed diagnosis
  • The treating clinician is of the opinion that the patient is appropriate for oral anticoagulation as per standard of care
  • Patient or legally authorized representative is able to give written informed consent

Exclusion criteria

  • Patient has known antiphospholipid antibody syndrome (APLS; lupus anticoagulant, anti-beta 2-glycoprotein I antibodies, and anticardiolipin antibody) by Sapporo-Sydney criteria with a previous history of venous or arterial thrombosis
  • Patient is anticipated to require invasive procedure (e.g. lumbar puncture, thrombectomy, hemicraniectomy) prior to initiation of oral anticoagulation**
  • Patient is unable to swallow due to depressed level of consciousness†
  • Impaired renal function (i.e., CrCl < 30 mL/min using Cockroft-Gault equation)
  • Pregnancy; if a woman is of childbearing potential a urine or serum beta human chorionic gonadotropin (β-hCG) test is positive
  • Breastfeeding at the time of randomization
  • Bleeding diathesis or other contraindication to anticoagulation
  • Any concurrent medical condition requiring mandatory antiplatelet or anticoagulant use
  • Concomitant use of strong CYP3A4 inducers (e.g., ongoing use of dilantin, carbamazepine, HIV protease inhibitors) or CYP3A4 inhibitors (e.g., diltiazem, ketoconazole)
  • Patient has a severe or fatal comorbid illness that will prevent improvement, or cannot complete follow-up due to the same, or cannot complete follow-up due to co-morbid non-fatal illness, non-residence in the city, or for any other known reason for which follow-up would be impossible.

Treatment and study plan

Rivaroxaban

Drug

Rivaroxaban 20 mg daily (15 mg daily in participants with a CrCl 30-49 mL/min as per the Cockroft-Gault equation)

Other names: Xarelto

Standard of care

Drug

Accepted standard of care as per American Heart Association/American Stroke Association Guidelines (initial use of unfractionated heparin or low-molecular weight heparin with transition to an oral vitamin K antagonist or continuation with low-molecular weight heparin) with choice of agent at the treating physician's discretion.

Other names: Heparin, Coumadin, Fragmin, Lovenox, Innohep

Primary outcomes

  1. Composite rate of all-cause mortality, symptomatic intracranial bleeding, major extracranial bleeding

    Time frame: 180 days

    Symptomatic intracranial bleeding is defined as a new symptomatic intracranial hemorrhage OR worsening existing intracranial hemorrhage with a >33% change in hematoma volume, AND either an NIHSS score increase of 4 or more points, or a change in level of consciousness as per NIHSS item 1a, AND the clinical change is thought to be attributable to the hemorrhage.

    Major extracranial bleeding is defined as bleeding in a critical area or organ, including intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a drop in hemoglobin by 20 g/L or more, leading to transfusion of 2 or more units of whole blood or red cells.

Secondary outcomes

  1. All-cause mortality

    Time frame: 180 days

    Death from any cause

  2. Symptomatic intracranial bleeding

    Time frame: 180 days

    Symptomatic intracranial bleeding is defined as a new symptomatic intracranial hemorrhage OR worsening existing intracranial hemorrhage with a >33% change in hematoma volume, AND either an NIHSS score increase of 4 or more points, or a change in level of consciousness as per NIHSS item 1a, AND the clinical change is thought to be attributable to the hemorrhage.

  3. Major extracranial bleeding

    Time frame: 180 days

    Major extracranial bleeding is defined as bleeding in a critical area or organ, including intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a drop in hemoglobin by 20 g/L or more, leading to transfusion of 2 or more units of whole blood or red cells.

  4. Recurrent venous thromboembolism

    Time frame: 180 days or end of anticoagulation, whichever is sooner

    any thrombosis at a new site including cerebral venous thrombosis in a separate localization from index event

  5. Major bleeding or clinically relevant non-major bleeding

    Time frame: 180 days or end of anticoagulation, whichever is sooner

    A clinically relevant minor bleed is an acute or subacute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of: (a) a hospital admission for bleeding, or (b) a physician guided medical or surgical treatment for bleeding, or (c) a change in antithrombotic therapy (including interruption or discontinuation or study drug)

  6. Partial or complete recanalization

    Time frame: 180 or 365 days

    Partial or complete recanalization between baseline and last study venogram

  7. Functional independence

    Time frame: 365 days

    modified Rankin Scale 0-1

  8. Reduced functional dependence

    Time frame: 365 days

    shift of one or more modified Rankin Scale categories to reduced functional dependence

  9. Health care resource utilization

    Time frame: 365 days

    Cost in Canadian dollars of number of hospitalizations (length of stay, critical care unit use), emergency room visits, unscheduled outpatient consultations, postacute care (including home care, rehabilitation stays or long-term care)

  10. Population Health Questionnaire (PHQ)-9 score

    Time frame: 365 days

    Change in PHQ-9 score between baseline and end of study

  11. EuroQOL 5-Dimensions (EQ-5D) score

    Time frame: 365 days

    Change in EQ-5D score between baseline and end of study

  12. Fatigue Assessment score

    Time frame: 365 days

    Change in fatigue assessment score between baseline and end of study

  13. Headache Impact Test - 6 score

    Time frame: 365 days

    Change in Headache Impact Test - 6 score between baseline and Day 180 (score = 36-78, where a higher score indicates a worse outcome)

  14. Montreal Cognitive Assessment score

    Time frame: 365 days

    Change in performance on the Montreal Cognitive Assessment between baseline and end of study (score = 0-30, where a higher score indicates a better outcome)

  15. National Institutes of Health toolbox - Cognitive battery score

    Time frame: 365 days

    Change in performance on the cognitive battery of the National Institutes of Health toolbox between baseline and end of study (where a higher score indicates a better outcome)

  16. Boston cookie theft picture description task

    Time frame: 365 days

    Change in spontaneous speech between baseline and end of study. Components of spontaneous speech include lexical features (part-of-speech, word types and frequencies), syntactic complexity, grammaticality, fluency, vocabulary richness, and acoustic features.

Sponsors and collaborators

Lead sponsor

University of British Columbia

Other

Registry information

Official study title

Multicentre, Prospective Randomized Open Label, Blinded-endpoint (PROBE) Controlled Trial of Early Anticoagulation With Rivaroxaban Versus Standard of Care in Determining Safety at 365 Days in Symptomatic Cerebral Venous Thrombosis

Acronym: SECRET

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Jun 7, 2017
Registry last updated
Dec 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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