Cerebral Venous ThrombosisPhase 2SECRETNCT03178864
Study of Rivaroxaban for CeREbral Venous Thrombosis
A Phase 2 study testing Rivaroxaban in people with Cerebral Venous Thrombosis, run by University of British Columbia at 11 sites in Canada.
Trial summary
SECRET examines the safety of rivaroxaban versus standard-of-care for treatment of symptomatic cerebral venous thrombosis, initiated within 14 days of diagnosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Venous Thrombosis
- What is being tested?
- Rivaroxaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 11 sitesCanada
- Study dates
- 12 Mar 2019to 5 Oct 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Canada11 sites
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Hamilton Health Sciences Centre
Hamilton, Ontario, L8L 2X2
Kelowna General Hospital
Kelowna, British Columbia, V1Y 1T2
London Health Sciences Centre
London, Ontario, N6A 5W9
Centre hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 0A9
The Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Vancouver General Hospital
Vancouver, British Columbia, V5Z1M9
About this study
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
SECRET examines the safety of rivaroxaban versus standard-of-care for treatment of symptomatic cerebral venous thrombosis, initiated within 14 days of diagnosis.
Read the 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.
- Conditions
- Cerebral Venous Thrombosis
- Being tested
- Rivaroxaban, Standard of care
- Keywords
- cerebral venous thrombosis, anticoagulation
- Medical subject headings
- Intracranial Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
Also called Xarelto
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
Also called Heparin, Coumadin, Fragmin, Lovenox, Innohep
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.
| Study group | Role | What they receive |
|---|---|---|
| Rivaroxaban | Experimental | Rivaroxaban Receives: Drug: Rivaroxaban |
| Standard of care | Active comparator | Unfractionated heparin Low-molecular weight heparin (dalteparin, enoxaparin, tinzaparin) Warfarin Receives: Drug: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 180 days
Secondary outcomes (16)
All-cause mortality
Death from any cause
Measured: 180 days
Symptomatic intracranial 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.
Measured: 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.
Measured: 180 days
Recurrent venous thromboembolism
any thrombosis at a new site including cerebral venous thrombosis in a separate localization from index event
Measured: 180 days or end of anticoagulation, whichever is sooner
Major bleeding or clinically relevant non-major bleeding
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)
Measured: 180 days or end of anticoagulation, whichever is sooner
Partial or complete recanalization
Partial or complete recanalization between baseline and last study venogram
Measured: 180 or 365 days
Functional independence
modified Rankin Scale 0-1
Measured: 365 days
Reduced functional dependence
shift of one or more modified Rankin Scale categories to reduced functional dependence
Measured: 365 days
Health care resource utilization
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)
Measured: 365 days
Population Health Questionnaire (PHQ)-9 score
Change in PHQ-9 score between baseline and end of study
Measured: 365 days
EuroQOL 5-Dimensions (EQ-5D) score
Change in EQ-5D score between baseline and end of study
Measured: 365 days
Fatigue Assessment score
Change in fatigue assessment score between baseline and end of study
Measured: 365 days
Headache Impact Test - 6 score
Change in Headache Impact Test - 6 score between baseline and Day 180 (score = 36-78, where a higher score indicates a worse outcome)
Measured: 365 days
Montreal Cognitive Assessment score
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)
Measured: 365 days
National Institutes of Health toolbox - Cognitive battery score
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)
Measured: 365 days
Boston cookie theft picture description task
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.
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2017
- Study start12 Mar 2019
- Primary completion5 Oct 2022
- Study completion5 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cerebral Venous ThrombosisStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thalia Field, University of British Columbia
- Investigators
- Thalia S Field, MD FRCPC, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03178864
- Sponsor's protocol ID
- H17-00440
- Acronym
- SECRET
- Status last verified
- Dec 2022
- First submitted
- 1 Jun 2017
- Last updated
- 14 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon completion of the SECRET Trial, a public use database will be prepared by stripping any and all personal identifiers. The public use database, consisting of several data files, should contain: (1) baseline and demographic characteristics; (2) outcomes assessments; (3) CT/MRI data; (4) concomitant medications and procedures; and (5) adverse events. Each data file is made available as a formatted SAS dataset or other electronic format. The data files are distributed along with the data dictionary and a brief instruction ("Readme") file. These data files will be made available to the public only after all major manuscripts (including secondary analysis papers) of the Trial are accepted for publication in peer-reviewed journals.
Publications
Field TS, Dizonno V, Almekhlafi MA, Bala F, Alhabli I, Wong H, Norena M, Villaluna MK, King-Azote P, Ratnaweera N, Mancini S, Van Gaal SC, Wilson LK, Graham BR, Sposato LA, Blacquiere D, Dewar BM, Boulos MI, Buck BH, Odier C, Perera KS, Pikula A, Tkach A, Medvedev G, Canfield C, Mortenson WB, Nadeau JO, Alshimemeri S, Benavente OR, Demchuk AM, Dowlatshahi D, Lanthier S, Lee AYY, Mandzia J, Suryanarayan D, Weitz JI, Hill MD; SECRET Investigators. Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis. Stroke. 2023 Nov;54(11):2724-2736. doi: 10.1161/STROKEAHA.123.044113. Epub 2023 Sep 7.
PubMed 37675613
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03178864
- Acronym / sponsor ID
- SECRET / H17-00440
- Conditions
- Cerebral Venous Thrombosis
- Keywords
- cerebral venous thrombosis, anticoagulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 12 Mar 2019 (actual)
- Primary completion
- 5 Oct 2022 (actual)
- Study completion
- 5 Oct 2022 (actual)
- First posted
- 7 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban | Experimental | Drug: RivaroxabanRivaroxaban |
| Standard of care | Active comparator | Drug: Standard of careUnfractionated heparin Low-molecular weight heparin (dalteparin, enoxaparin, tinzaparin) Warfarin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivaroxabanAlso: XareltoRivaroxaban 20 mg daily (15 mg daily in participants with a CrCl 30-49 mL/min as per the Cockroft-Gault equation) | Drug | Rivaroxaban |
| Standard of careAlso: Heparin, Coumadin, Fragmin, Lovenox, InnohepAccepted 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. | Drug | Standard of care |
Primary outcome
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.
16 secondary outcomes
All-cause mortality
Time frame: 180 days
Symptomatic intracranial bleeding
Time frame: 180 days
Major extracranial bleeding
Time frame: 180 days
Recurrent venous thromboembolism
Time frame: 180 days or end of anticoagulation, whichever is sooner
Major bleeding or clinically relevant non-major bleeding
Time frame: 180 days or end of anticoagulation, whichever is sooner
Partial or complete recanalization
Time frame: 180 or 365 days
Functional independence
Time frame: 365 days
Reduced functional dependence
Time frame: 365 days
Health care resource utilization
Time frame: 365 days
Population Health Questionnaire (PHQ)-9 score
Time frame: 365 days
EuroQOL 5-Dimensions (EQ-5D) score
Time frame: 365 days
Fatigue Assessment score
Time frame: 365 days
Headache Impact Test - 6 score
Time frame: 365 days
Montreal Cognitive Assessment score
Time frame: 365 days
National Institutes of Health toolbox - Cognitive battery score
Time frame: 365 days
Boston cookie theft picture description task
Time frame: 365 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2022.
- Derived from this study: PubMed 37675613Field TS, Dizonno V, Almekhlafi MA, Bala F, Alhabli I, Wong H, Norena M, Villaluna MK, King-Azote P, Ratnaweera N, Mancini S, Van Gaal SC, Wilson LK, Graham BR, Sposato LA, Blacquiere D, Dewar BM, Boulos MI, Buck BH, Odier C, Perera KS, Pikula A, Tkach A, Medvedev G, Canfield C, Mortenson WB, Nadeau JO, Alshimemeri S, Benavente OR, Demchuk AM, Dowlatshahi D, Lanthier S, Lee AYY, Mandzia J, Suryanarayan D, Weitz JI, Hill MD; SECRET Investigators. Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis. Stroke. 2023 Nov;54(11):2724-2736. doi: 10.1161/STROKEAHA.123.044113. Epub 2023 Sep 7.
- Individual participant dataSharing planned: Yes. Upon completion of the SECRET Trial, a public use database will be prepared by stripping any and all personal identifiers. The public use database, consisting of several data files, should contain: (1) baseline and demographic characteristics; (2) outcomes assessments; (3) CT/MRI data; (4) concomitant medications and procedures; and (5) adverse events. Each data file is made available as a formatted SAS dataset or other electronic format. The data files are distributed along with the data dictionary and a brief instruction ("Readme") file. These data files will be made available to the public only after all major manuscripts (including secondary analysis papers) of the Trial are accepted for publication in peer-reviewed journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thalia S Field, MD FRCPC principal investigator
University of British Columbia
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rivaroxaban in people with Cerebral Venous Thrombosis, run by University of British Columbia at 11 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite rate of all-cause mortality, symptomatic intracranial bleeding, major extracranial bleeding (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03178864, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2022.