Rivaroxaban vs. Warfarin in CVT Treatment

NCT04569279 | Completed Phase 3

• 1 other identifier: 3934
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral venous thrombosis (CVT) is an uncommon venous-type of stroke tends to affect younger patients with somewhat different risk factors and much better outcome compared to arterial strokes. Anti-coagulation is the standard of treatment for patients with (CVT) initially with heparins followed by other oral blood thinners for several months. In this study, the investigators are comparing warfarin with another well-known blood thinner, rivaroxaban, which has a fixed once-daily dose with no need for monitoring in terms of clinical outcomes and complications.

Conditions

Cerebral Vein Thrombosis

Keywords

cerebral vein thrombosis; stroke; cerebral vascular accidents; hemorrhagic stroke; intracranial bleeding; intracranial pressure; venous flow; thrombus; oral contraceptives; hormone replacement therapy; pregnancy; puerperium; prothrombotic conditions; headache; seizures; anticoagulation; thrombotic events; unfractionated heparin; low molecular weight heparin; warfarin; rivaroxaban; acetazolamide; RWCVT; CVT; CVA; UFH; LMWH; CSF; ICP; OCP; CT; MRI; INR

Outcome Measures

Primary Outcomes (1)

• Change of sinus venous thrombosis severity scale (SVTSS)

  it was designed by Einhaupl 1991 who performed with his colleagues the first clinical trial of heparin in (CVT) Patients score is given to each of the 4 categories as follows: 1. Headache: (1: slight, 2: moderate, 3: severe) 2. Focal signs: (1: transient or minimum hypesthesia, 2: transient or slight paresis, 3: mild paresis, 4: moderate paresis, 5: severe paresis or plegia) 3. seizures: (3: seizures (no series or status), 4: series or status) 4. consciousness: (5: confused or psychotic, 6: somnolent, 7: stupor, 8: coma, 9: dead). Please refer to appendix 1 for more details

  SVTSS score will be evaluated at the point of admission, and each month after for 6 months later

Secondary Outcomes (1)

• Change of Barthel index

  Barthel index will be evaluated at the point of admission, and each month after for 6 months later

Other Outcomes (4)

• Change of intracranial pressure ICP

  ICP will be evaluated at the point of admission, and each month after for 6 months later

• Development of symptomatic intracranial hemorrhage (ICH)

  Within 6 months of follow up after discharge, patients will be monitored for any new symptom suggesting ICH to be investigated and managed when necessary.

• Development of major extra-cranial bleeding (MECB)

  Within 6 months of follow up after discharge, patients will be monitored for any new symptom suggesting MECB to be investigated and managed when necessary.

Study Arms (2)

Warfarin arm

ACTIVE COMPARATOR

Patients randomly assigned to (W) group will receive an adjusted dose of warfarin with targeted INR of 2.0 to 3.0.

Drug: Warfarin

Rivaroxaban arm

EXPERIMENTAL

Patients randomly assigned to (R) group will receive 20mg rivaroxaban daily if CrCl\>50 mL/min using Cockcroft-Gault equation or 15mg rivaroxaban daily if CrCl 30-50 mL/min.

Drug: Rivaroxaban

Interventions

Rivaroxaban DRUG

Rivaroxaban (Rovaltro®) is a novel oral anticoagulant that acts selectively, reversibly, and potently on activated Factor X (Factor Xa) inhibiting a critical point on the coagulation cascade. Rivaroxaban has excellent bioavailability, rapid onset of peak anticoagulation effect, and predictable pharmacokinetic and pharmacodynamic properties making routine laboratory monitoring and dose adjustments almost unnecessary (11). Rivaroxaban is an extensively studied drug and has received approvals for anticoagulation in several preventive and therapeutic indications (11). Now medical literature has some solid evidence that Rivaroxaban is comparable with other anticoagulants in terms of efficacy. Several studies imply that Rivaroxaban may have a lower risk of major bleeding (11). Several reports and small case-series (12,13) suggest that rivaroxaban may be beneficial as Warfarin in the treatment of cerebral venous thrombosis (CVT) with less or no major complications.

Also known as: Rovaltro®

Rivaroxaban arm

Warfarin DRUG

Warfarin (Orfarin®) is the most popular vitamin K antagonist and is considered the standard of care in many venous and arterial anticoagulation indications with extensive clinical experience regarding its use. This inexpensive and effective drug has a narrow therapeutic window that is affected by diet changing and many drug interactions, making frequent monitoring with prothrombin time (PT)/international normalized ratio (INR) highly important.(14)

Also known as: Orfarin®

Warfarin arm

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• patients aged 14 years or older and weighing more than 50 kg.
• Recent diagnosis of symptomatic cerebral venous thrombosis confirmed by MRI modalities, CT venography, or conventional angiography.

You may not qualify if:

• Any absolute contraindication to anticoagulation.
• Impaired renal function (CrCl \< 30 mL/min using Cockcroft-Gault equation).
• Pregnancy or lactation at randomization.
• mandatory other blood thinners use (e.g. Aspirin).

Sponsors & Collaborators

• Damascus University: lead

Study Sites (1)

Damascus University

Damascus, Damascus Governorate, Syria

Location

Related Publications (19)

• Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Apr;42(4):1158-92. doi: 10.1161/STR.0b013e31820a8364. Epub 2011 Feb 3.

  PMID: 21293023 BACKGROUND

• Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004 Mar;35(3):664-70. doi: 10.1161/01.STR.0000117571.76197.26. Epub 2004 Feb 19.

  PMID: 14976332 BACKGROUND

• Bushnell C, Saposnik G. Evaluation and management of cerebral venous thrombosis. Continuum (Minneap Minn). 2014 Apr;20(2 Cerebrovascular Disease):335-51. doi: 10.1212/01.CON.0000446105.67173.a8.

  PMID: 24699485 BACKGROUND

• Schaller B, Graf R. Cerebral venous infarction: the pathophysiological concept. Cerebrovasc Dis. 2004;18(3):179-88. doi: 10.1159/000079939. Epub 2004 Jul 22.

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• Crassard I, Bousser MG. [Headache in patients with cerebral venous thrombosis]. Rev Neurol (Paris). 2005 Jul;161(6-7):706-8. doi: 10.1016/s0035-3787(05)85124-0. French.

  PMID: 16141966 BACKGROUND

• Coutinho J, de Bruijn SF, Deveber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD002005. doi: 10.1002/14651858.CD002005.pub2.

  PMID: 21833941 BACKGROUND

• Einhaupl KM, Villringer A, Meister W, Mehraein S, Garner C, Pellkofer M, Haberl RL, Pfister HW, Schmiedek P. Heparin treatment in sinus venous thrombosis. Lancet. 1991 Sep 7;338(8767):597-600. doi: 10.1016/0140-6736(91)90607-q.

  PMID: 1679154 BACKGROUND

• Lijfering WM, Brouwer JL, Veeger NJ, Bank I, Coppens M, Middeldorp S, Hamulyak K, Prins MH, Buller HR, van der Meer J. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood. 2009 May 21;113(21):5314-22. doi: 10.1182/blood-2008-10-184879. Epub 2009 Jan 12.

  PMID: 19139080 BACKGROUND

• Martinelli I, Bucciarelli P, Passamonti SM, Battaglioli T, Previtali E, Mannucci PM. Long-term evaluation of the risk of recurrence after cerebral sinus-venous thrombosis. Circulation. 2010 Jun 29;121(25):2740-6. doi: 10.1161/CIRCULATIONAHA.109.927046. Epub 2010 Jun 14.

  PMID: 20547928 BACKGROUND

• Sarich TC, Peters G, Berkowitz SD, Misselwitz F, Nessel CC, Burton P, Cook-Bruns N, Lensing AW, Haskell L, Perzborn E, Kubitza D, Moore KT, Jalota S, Weber J, Pan G, Sun X, Westermeier T, Nadel A, Oppenheimer L, DiBattiste PM. Rivaroxaban: a novel oral anticoagulant for the prevention and treatment of several thrombosis-mediated conditions. Ann N Y Acad Sci. 2013 Jul;1291:42-55. doi: 10.1111/nyas.12136. Epub 2013 May 23.

  PMID: 23701516 BACKGROUND

• Geisbusch C, Richter D, Herweh C, Ringleb PA, Nagel S. Novel factor xa inhibitor for the treatment of cerebral venous and sinus thrombosis: first experience in 7 patients. Stroke. 2014 Aug;45(8):2469-71. doi: 10.1161/STROKEAHA.114.006167. Epub 2014 Jun 24.

  PMID: 25070963 BACKGROUND

• 13. Anticoli S, Pezzella FR, Scifoni G, et al. Treatment of Cerebral Venous Thrombosis with Rivaroxaban. J Biomedical Sci. 2016, 5:3

  BACKGROUND

• Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e44S-e88S. doi: 10.1378/chest.11-2292.

  PMID: 22315269 BACKGROUND

• Gloth FM 3rd, Scheve AA, Stober CV, Chow S, Prosser J. The Functional Pain Scale: reliability, validity, and responsiveness in an elderly population. J Am Med Dir Assoc. 2001 May-Jun;2(3):110-4.

  PMID: 12812581 BACKGROUND

• MAHONEY FI, BARTHEL DW. FUNCTIONAL EVALUATION: THE BARTHEL INDEX. Md State Med J. 1965 Feb;14:61-5. No abstract available.

  PMID: 14258950 BACKGROUND

• Frisen L. Swelling of the optic nerve head: a staging scheme. J Neurol Neurosurg Psychiatry. 1982 Jan;45(1):13-8. doi: 10.1136/jnnp.45.1.13.

  PMID: 7062066 BACKGROUND

• RANKIN J. Cerebral vascular accidents in patients over the age of 60. II. Prognosis. Scott Med J. 1957 May;2(5):200-15. doi: 10.1177/003693305700200504. No abstract available.

  PMID: 13432835 BACKGROUND

• Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.

  PMID: 15842354 BACKGROUND

• Alkhawam A, Okar L, Hanafi I, Murin P, Ibrahim A, Isstaif J, Khashaneh E, Morsi RZ, Kass-Hout T. Rivaroxaban Versus Warfarin for the Treatment of Cerebral Venous Thrombosis (RWCVT): A Randomized Controlled Trial in Resource-Limited Setting. Stroke Res Treat. 2025 May 5;2025:8893742. doi: 10.1155/srat/8893742. eCollection 2025.

  PMID: 40376280 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Intracranial Thrombosis; Stroke; Hemorrhagic Stroke; Intracranial Hemorrhages; Thrombosis; Headache; Seizures

Interventions

Rivaroxaban; Warfarin

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; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: all patients will receive a weight-adjusted dose of low molecular weight heparins (LMWH) immediately after the diagnosis of (CVT) for several days as needed. Subjects will be randomly assigned to one of the two oral anticoagulation treatment groups (Rivaroxaban (R) group and Warfarin (W) group) when they can take oral medications. Subjects will be followed up monthly for 6 months to evaluate primary and secondary outcomes.

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: September 29, 2020
• Study Start: September 1, 2017
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

SY (1)