SECRET: Study of Rivaroxaban for CeREbral Venous Thrombosis

• Sponsor: University of British Columbia (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03178864
• Collaborator: (none)
• Enrollment: 50
• Locations: 13
• Arms: 2
• Anticipated Duration (Months): 44.7
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cerebral Venous Thrombosis	Drug: Rivaroxaban; Drug: Standard of care	Phase 2

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

• Study Type: Interventional
• Anticipated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 12, 2019
• Anticipated Primary Completion Date: Oct 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban Rivaroxaban	Drug: Rivaroxaban; 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
Active Comparator: Standard of care Unfractionated heparin Low-molecular weight heparin (dalteparin, enoxaparin, tinzaparin) Warfarin	Drug: Standard of care; 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

Outcome Measures

Primary Outcome Measures

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

1. All-cause mortality [180 days]

   Death from any cause

2. Symptomatic intracranial bleeding [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 [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 [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 [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 [180 or 365 days]

   Partial or complete recanalization between baseline and last study venogram

7. Functional independence [365 days]

   modified Rankin Scale 0-1

8. Reduced functional dependence [365 days]

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

9. Health care resource utilization [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 [365 days]

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

11. EuroQOL 5-Dimensions (EQ-5D) score [365 days]

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

12. Fatigue Assessment score [365 days]

    Change in fatigue assessment score between baseline and end of study

13. Headache Impact Test - 6 score [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 [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Foothills Medical Centre	Calgary	Alberta	Canada	T2N 2T9
2	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
3	Kelowna General Hospital	Kelowna	British Columbia	Canada	V1Y 1T2
4	Royal Columbian Hospital	New Westminster	British Columbia	Canada	V3L 3W7
5	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z1M9
6	Hamilton Health Sciences Centre	Hamilton	Ontario	Canada	L8L 2X2
7	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
8	London Health Sciences Centre	London	Ontario	Canada	N6A 5W9
9	The Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1Y 4E9
10	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
11	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
12	Centre hospitalier de l'Université de Montréal	Montréal	Quebec	Canada
13	Royal University Hospital	Saskatoon	Saskatchewan	Canada	S7N 0W8

Sponsors and Collaborators

• University of British Columbia

Investigators

• Principal Investigator: Thalia S Field, MD FRCPC, University of British Columbia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Thalia Field, Principal Investigator, University of British Columbia
• ClinicalTrials.gov Identifier: NCT03178864
• Other Study ID Numbers: H17-00440
• First Posted: Jun 7, 2017
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Thalia Field, Principal Investigator, University of British Columbia: cerebral venous thrombosis; anticoagulation
• Additional relevant MeSH terms: Thrombosis; Venous Thrombosis; Heparin; Rivaroxaban

Study Results

No Results Posted as of Sep 28, 2021