Study of Rivaroxaban for CeREbral Venous Thrombosis

NCT03178864 | Completed Phase 2 DMC

• 1 other identifier: H17-00440
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 11

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.

Conditions

Cerebral Venous Thrombosis

Keywords

cerebral venous thrombosis; anticoagulation

Outcome Measures

Primary Outcomes (1)

• 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.

  180 days

Secondary Outcomes (16)

• All-cause mortality

  180 days

• Symptomatic intracranial bleeding

  180 days

• Major extracranial bleeding

  180 days

• Recurrent venous thromboembolism

  180 days or end of anticoagulation, whichever is sooner

• Major bleeding or clinically relevant non-major bleeding

  180 days or end of anticoagulation, whichever is sooner

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

Rivaroxaban

Drug: Rivaroxaban

Standard of care

ACTIVE COMPARATOR

Unfractionated heparin Low-molecular weight heparin (dalteparin, enoxaparin, tinzaparin) Warfarin

Drug: Standard of care

Interventions

Rivaroxaban DRUG

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

Also known as: Xarelto

Rivaroxaban

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.

Also known as: Heparin, Coumadin, Fragmin, Lovenox, Innohep

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (11)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Kelowna General Hospital

Kelowna, British Columbia, V1Y 1T2, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z1M9, Canada

Location

Hamilton Health Sciences Centre

Hamilton, Ontario, L8L 2X2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

The Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 0A9, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Related Publications (1)

• 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.

  PMID: 37675613 DERIVED

MeSH Terms

Conditions

Intracranial Thrombosis

Interventions

Rivaroxaban; Standard of Care; Heparin; Warfarin; Dalteparin; Enoxaparin; Tinzaparin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Glycosaminoglycans; Polysaccharides; Carbohydrates; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heparin, Low-Molecular-Weight

Study Officials

• Thalia S Field, MD FRCPC

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 7, 2017
• Study Start: March 12, 2019
• Primary Completion: October 5, 2022
• Study Completion: October 5, 2022
• Last Updated: December 14, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share

Locations

CA (11)