Clinical trial NCT03178864: Study of Rivaroxaban for CeREbral Venous Thrombosis
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cerebral Venous Thrombosis
Keywords: cerebral venous thrombosis
anticoagulation
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2017-06-07
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite rate of all-cause mortality, symptomatic intracranial bleeding, major extracranial bleeding
timeFrame: 180 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: 180 days
measure: Symptomatic intracranial bleeding
timeFrame: 180 days
measure: Major extracranial bleeding
timeFrame: 180 days
measure: Recurrent venous thromboembolism
timeFrame: 180 days or end of anticoagulation, whichever is sooner
measure: Major bleeding or clinically relevant non-major bleeding
timeFrame: 180 days or end of anticoagulation, whichever is sooner
measure: Partial or complete recanalization
timeFrame: 180 or 365 days
measure: Functional independence
timeFrame: 365 days
measure: Reduced functional dependence
timeFrame: 365 days
measure: Health care resource utilization
timeFrame: 365 days
measure: Population Health Questionnaire (PHQ)-9 score
timeFrame: 365 days
measure: EuroQOL 5-Dimensions (EQ-5D) score
timeFrame: 365 days
measure: Fatigue Assessment score
timeFrame: 365 days
measure: Headache Impact Test - 6 score
timeFrame: 365 days
measure: Montreal Cognitive Assessment score
timeFrame: 365 days
measure: National Institutes of Health toolbox - Cognitive battery score
timeFrame: 365 days
measure: Boston cookie theft picture description task
timeFrame: 365 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: University of British Columbia
name: Thalia S Field, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References: