Comparison of the Efficacy of Rivroxaban to Coumadin( Warfarin ) in Cerebral Venous Thrombosis (CVT)

In past few years new anticoagulants have been developed which directly inhibit thrombin or factor X.factor x inhibitor is available in Pakistan. The superior efficacy of Rivroxaban has been shown in Deep Venous Thrombosis in EINSTEIN study (3).Its definite superiority in prevention of embolic stroke in nonvalvular atrial fibrillation is evidenced by the study ROCKET AF (4). With Rivroxaban no monitoring is required, and also there are no drug interactions .There are few pilot studies of using Rivroxaban in cerebral venous thrombosis. This study is therefore required to find its efficacy in CVT patients as well as its comparison with Coumadin

Study Overview

• Status: Unknown
• Conditions: Cerebral Venous Thrombosis
• Intervention / Treatment: Drug: Coumadin; Drug: Rivoroxaban

Detailed Description

Cerebral venous thrombosis is rare form of stroke, accounting .5 to 1% only (1)Exact estimate for Pakistani population is not known Mubarak et al described 6- year imaging incidence and prevalence of CVST to be 10.22% and 11.055% respectively(2) .Majority of cerebral venous stroke patients are females in reproductive age. Coumadin is one of the notorious drugs to be used in pregnancy categorized as X. it also has many drug interactions .and there are diet restrictions too being on Coumadin. It also requires maintanence of prothrombin time in certain range which means patient has to go under phlebotomy at least twice a month. Moreover not all laboratories are well equipped resulting in poor test sensitivity. and at times clinicians keep patients on suboptimum doses for fear of bleeding ending with poor efficacy.

In past few years new anticoagulants have been developed which directly inhibit thrombin or factor X.factor x inhibitor is available in Pakistan.

The superior efficacy of Rivroxaban has been shown in Deep Venous Thrombosis in EINSTEIN study (3).Its definite superiority in prevention of embolic stroke in nonvalvular atrial fibrillation is evidenced by the study ROCKET AF (4). With Rivroxaban no monitoring is required, and also there are no drug interactions .There are few pilot studies of using Rivroxaban in cerebral venous thrombosis. This study is therefore required to find its efficacy in CVT patients as well as its comparison with Coumadin .

OBJECTIVE To Compare the efficacy of Rivroxaban to Warfarin in Cerebral Venous Thrombosis MATERIAL AND METHODS STUDY DESIGN: Quasi Experimental; Descriptive cross sectional

DURATION OF STUDY:

6 months to 1 year

SAMLE SIZE :

50 patients SAMPLING TECHNIQUE : Consecutive (non probability) sampling.

INCLUSION CRITERIA:

Patients of either gender Age between 13 years and 50 years Patients with proven CVT on neuro imaging (CTV, o MRV)

EXCLUSION CRITERIA:

Patients suffering from Chronic Liver disesase Patients having contraindications for oral anticoagulation Patients suffering from hematological or brain malignancy Patients whose MRV and CTV do not support CVT

DATA COLLECTION PROCEDURE After taking permission from hospital ethical review committee , All patients with confirmed CVT based on established criteria using any NOAC or WARFARIN presenting to PIMS or FFH hospitals will be enrolled. Data will be obtained by retrospective manner if they are using anticoagulants for more than 6 months. If patients are using anticoagulants for less than 6 months, they will be enrolled and followed up for six months.

DATA ANALYSIS The data will be analyzed using SPSS version 16.0. Descriptive analysis will be done and reported as mean ± SD for continuous variables like age whereas frequencies and percentages will be calculated for categorical variables such as gender, individual risk factors.

P-value ≤ 0.05 will be significant. Results will be presented in tabulated or graphical forms.

Outcome measures Outcome measures will include any hemorrhage or recurrent CVT based on repeat MRI.

MRs Scale Secondary Outcome Comparison of cost of two treatment groups.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saira Saad, MBBS,MRCP,FCPS(Neurology); Phone Number: +92 334 9555 456; Email: sairaiqbl@hotmail.com
• Study Contact Backup: Name: Haris Majid, MBBS,FCPS(Neurology); Phone Number: +92 333 516 3322; Email: harismajid@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients of either gender Age between 13 years and 50 years Patients with proven CVT on neuro imaging (CTV, o MRV) -

Exclusion Criteria:

Patients suffering from Chronic Liver disesase Patients having contraindications for oral anticoagulation Patients suffering from hematological or brain malignancy Patients whose MRV and CTV do not support CVT

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Coumadin Group; Patients in Coumadin Group would be administered Coumadin with overlap of heparin for first two days followed by Coumadin given orally ,dose being adjusted according to INR .The INR range would be between 2-3.it would be given once a day.The total duration OFf coumadin would be six months.	Drug: Coumadin; Patients in Coumadin Group would be administered Coumadin with overlap of heparin for first two days followed by Coumadin given orally ,dose being adjusted according to INR .The INR range would be between 2-3.it would be given once a day. The total duration Of coumadin would be six months.
Active Comparator: Rivoroxaban Group; The dose protocol would be similar to the one used in Deep Venous Thrombosis. 15 mg PO q12hr for 21 days with food, THEN 20 mg PO qDay for 6 months.	Drug: Rivoroxaban; The dose protocol would be similar to the one used in Deep Venous Thrombosis. 15 mg PO q12hr for 21 days with food, Then 20 mg PO qDay for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemorrhage or Recurrent CVT based on repeat MRI.	Outcome measures will include any hemorrhage or recurrent CVT based on repeat MRI.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost	Comparison of cost of two treatment groups.	6 months

Collaborators and Investigators

• Sponsor: Foundation University Islamabad
• Collaborators: Shaheed Zulfiqar Ali Bhutto Medical University

Publications and helpful links

General Publications

• Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
• Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005 Apr 28;352(17):1791-8. doi: 10.1056/NEJMra042354. No abstract available.
• F. Mubarak, A. Muhammad, Cerebral venous sinus thrombosis: Incidence, prevalence and patterns of neurological involvement: a retrospective study from Pakistani population European society of Radiology .
• EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. doi: 10.1056/NEJMoa1007903. Epub 2010 Dec 3.
• Anticoli S, Pezzella FR, Scifoni G, et al. Treatment of Cerebral Venous Thrombosis with Rivaroxaban. J Biomedical Sci.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2017
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: June 15, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): June 19, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Anticoagulants; Warfarin
• Other Study ID Numbers: FUI/CTR/2017/2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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