Study of Rivaroxaban for CeREbral Venous Thrombosis

University of British Columbia55 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Cerebral Venous Thrombosis

Interventions

RivaroxabanDRUG

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

Standard of careDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Patients aged 18 and above 2. New diagnosis of symptomatic cerebral venous thrombosis as confirmed on CT venogram or MR venogram 3. Ability to randomize within 14 days of neuroimaging-confirmed diagnosis 4. The treating clinician is of the opinion that the patient is appropriate for oral anticoagulation as per standard of care 5. Patient or legally authorized representative is able to give written informed consent Exclusion criteria: 1. 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 2. Patient is anticipated to require invasive procedure (e.g. lumbar puncture, thrombectomy, hemicraniectomy) prior to initiation of oral anticoagulation\*\* 3. Patient is unable to swallow due to depressed level of consciousness† 4. Impaired renal function (i.e., CrCl \< 30 mL/min using Cockroft-Gault equation) 5. Pregnancy; if a woman is of childbearing potential a urine or serum beta human chorionic gonadotropin (β-hCG) test is positive 6. Breastfeeding at the time of randomization 7. Bleeding diathesis or other contraindication to anticoagulation 8. Any concurrent medical condition requiring mandatory antiplatelet or anticoagulant use 9. Concomitant use of strong CYP3A4 inducers (e.g., ongoing use of dilantin, carbamazepine, HIV protease inhibitors) or CYP3A4 inhibitors (e.g., diltiazem, ketoconazole) 10. 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.

Locations (11)

Foothills Medical Centre

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Kelowna General Hospital

Kelowna, British Columbia, Canada

Outcomes

Primary Outcomes

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

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.

Time frame: 180 days

Secondary Outcomes

All-cause mortality

Death from any cause

Time frame: 180 days

Symptomatic intracranial bleeding

Time frame: 180 days

Major extracranial bleeding

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.

Time frame: 180 days

Recurrent venous thromboembolism

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

Data from ClinicalTrials.gov

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