Dabigatran Versus Rivaroxaban in Cerebral Venous Thrombosis

Dabigatran Versus Rivaroxaban in Cerebral Venous Thrombosis, a Randomized Controlled Trial

Along with the current clinical trial, the efficacy and safety of a 150 mg Bid dabigatran administered within 24 hours of randomization after having first-ever cerebral venous thrombosis compared to 20 mg rivaroxaban were assessed through rate of recurrent VTE, mRS, rate of venous recanalization, HIT score, MoCA test, and central and peripheral hemorrhagic complications

Study Overview

• Status: Recruiting
• Conditions: Cerebral Venous Sinus Thrombosis
• Intervention / Treatment: Drug: Dabigatran Etexilate 150mg; Drug: Rivaroxaban 20 MG Oral Tablet

Detailed Description

The investigators conducted a single-blinded randomized controlled trial between August 2024 and September 2026 after the ethics committee of the faculty of medicine at Kafr el-Sheik University approved it.

The investigators got written informed consent from all eligible patients or their first order of kin before randomization.

The study will be composed of 2 arms rivaroxaban arm, which consisted of 100 patients who received 150 mg Bid dabigatran for 6 months, and the rivaroxaban arm, consisting of 100 patients who received 20mg rivaroxaban daily for 6 months

Study Procedures:

Every patient in our study will undergo:

Clinical workup: History, clinical assessment, NIHSS, MoCA, HIT-6, and mRS were recorded at baseline and at 30,90,180 days as a follow-up.

Detection of Risk Factors & Profiles:

Echocardiography TTE: in indicated patients ECG Monitoring: daily ECG monitoring will be performed in indicated patients. 3- Carotid Duplex: carotid duplex in indicated patients.

4- ESR & Lipid Profile& liver functions: All will be tested routinely for all patients.

5- Non-contrast CT brain and CTV on admission or MRI and MRV:, at baseline and after 6 months of treatment CT brain: Any patient with unexplained clinical deterioration at any time throughout his/her hospital stay will be urgently imaged by CT.

Primary End Point:

The primary efficacy outcome was the rate of Proportion of subjects with partial or complete venous recanalization by Day 180, and the primary safety outcome was the rate of drug hemorrhagic complications using the PLATO bleeding definition.

• Secondary End Point: The secondary efficacy outcomes were to evaluate the rates of patients who achieved a favorable outcome with (mRS = 0-2) after one week and after 180 days in a face-to-face interview in the outpatient clinic, Proportion of subjects with recurrent venous thromboembolism (any thrombosis at a new site, including cerebral venous thrombosis in a separate location from the index event) at Day 180 or the end of anticoagulation, whichever is sooner, rates of a composite of pulmonary embolism, DVT, myocardial infarction, and death due to vascular events after 180 days of follow-up, the MoCA, HIT-6 by 180 days, while the secondary safety outcome was the rate of treatment-related adverse effects assessed by a follow-up questionnaire

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
• Study Contact Backup: Name: sherihan R. ahmed, MD; Phone Number: 2001113432342; Email: sherihan_rezq@med.kfs.edu.eg

Study Locations

• Egypt
  • Kafr Ash Shaykh, Egypt, 33511
    • Recruiting
    • Kafr Elsheikh University Hospital
    • Contact: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
    • Contact: sherihan R. ahmed, MD; Phone Number: 2001007481842; Email: sherihan_rezq@med.kfs.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1-Patients aged 18 and above 2-New diagnosis of symptomatic cerebral venous thrombosis as confirmed on CT/CT venogram or MRI/MR venogram 3-Ability to randomize within 14 days of neuroimaging-confirmed diagnosis 4-The treating clinician thinks that the patient is appropriate for oral anticoagulation as per the standard of care 5-The patient or legally authorized representative can give written informed consent

Exclusion Criteria:

1. The patient has known antiphospholipid antibody syndrome with a previous history of venous or arterial thrombosis
2. The patient is anticipated to require invasive procedures (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 CockroftGault 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: dabigatran; 100 CVT patients will receive dabigatran 150mg Bid for 6 months.	Drug: Dabigatran Etexilate 150mg; 100 CVT patients will receive dabigatran 150mg Bid for 6 months. We will assess the Proportion of subjects who have partial or complete venous recanalization by Day 180 the rate of drug hemorrhagic complications using the PLATO bleeding definition, and the rates of patients who achieved a favorable outcome with (mRS = 0-2) after one week and after 180 days in a face-to-face interview in the outpatient clinic, Proportion of subjects with recurrent venous thromboembolism (any thrombosis at a new site, including cerebral venous thrombosis in a separate location from the index event) at Day 180 or the end of anticoagulation, whichever is sooner, rates of a composite of pulmonary embolism, DVT, myocardial infarction, and death due to vascular events after 180 days of follow-up, the MoCA, HIT-6 by 180 days, the rate of treatment-related adverse effects assessed by a follow-up questionnaire.; Other Names: group A
Active Comparator: rivaroxaban; 100 CVT patients will receive Rivaroxaban 20mg daily for 6 months.	Drug: Rivaroxaban 20 MG Oral Tablet; 100 CVT patients will receive Rivaroxaban 20mg daily for 6 months. We will assess the Proportion of subjects who have partial or complete venous recanalization by Day 180 the rate of drug hemorrhagic complications using the PLATO bleeding definition, and the rates of patients who achieved a favorable outcome with (mRS = 0-2) after one week and after 180 days in a face-to-face interview in the outpatient clinic, Proportion of subjects with recurrent venous thromboembolism (any thrombosis at a new site, including cerebral venous thrombosis in a separate location from the index event) at Day 180 or the end of anticoagulation, whichever is sooner, rates of a composite of pulmonary embolism, DVT, myocardial infarction, and death due to vascular events after 180 days of follow-up, the MoCA, HIT-6 by 180 days, the rate of treatment-related adverse effects assessed by a follow-up questionnaire.; Other Names: group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects who have partial or complete venous recanalization by Day 180	the investigators will perform magnetic resonance venography for all patients after 6 months to show if there is partial or complete recanalization of the affected venous sinus	180 days
Rate of drug-related hemorrhagic complications	the rate of drug hemorrhagic complications which was evaluated using the PLATO bleeding definition which classified hemorrhagic complications into three types as follows: Major bleeding which had one or more of the following criteria: fatal bleeding, intracranial, intrapericardial, bleeding associated with reduction of hemoglobin > 3-5 g/dl, bleeding required transfusion of two to four units whole blood or PRBCs, bleeding produced hypovolemic shock or severe hypotension that required pressor or surgery; Minor bleeding that required medical intervention to stop or treat bleeding: Minimal bleeding: any bleeding that did not require intervention or treatment such as bruising, bleeding gums, oozing from injection sites.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
value of Modified Rankin Scale (mRS) at six months	mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Its value ranges from 0 to 6; the lower the score, the better the stroke outcome. A favorable stroke outcome is considered with an mRS value equal to two or less.	6 months
value of HIT-6 score in each group after six months of treatment	The investigators assessed the absolute change in HIT6 score, the Headache Impact Test-6 (HIT-6) assessed the burden of headache in each group; the HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress, the patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often," or "always." These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent. It has four impact grades: little-to-no impact (HIT-6 score: 36-49), moderate impact (HIT-6 score: 50-55), substantial impact (HIT-6 score: 56-59), and severe impact (HIT-6 score: 60-78)	6 months
rate of drug adverse effects	Drug adverse effects: all non-hemorrhagic side effects related to the drugs of our study will be reported	6 months
The proportion of participants with recurrent venous thromboembolism	The investigators will assess the proportion of participants with recurrent venous thromboembolism (any thrombosis at a new site, including CVT in a separate location from the index event) during 6 months of treatment	6 months
rate of composite pulmonary embolism, myocardial infarction, and death due to vascular events	The investigators will assess the proportion of participants with pulmonary embolism, myocardial infarction, and death due to vascular events at during 6 months of treatment	6 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Investigators: Principal Investigator: mohamed G. Zeinhom, MD, neurology department kafr el-sheikh university

Publications and helpful links

General Publications

• Meyer DM, Albright KC, Allison TA, Grotta JC. LOAD: a pilot study of the safety of loading of aspirin and clopidogrel in acute ischemic stroke and transient ischemic attack. J Stroke Cerebrovasc Dis. 2008 Jan-Feb;17(1):26-9. doi: 10.1016/j.jstrokecerebrovasdis.2007.09.006.
• Paciaroni M, Ince B, Hu B, Jeng JS, Kutluk K, Liu L, Lou M, Parfenov V, Wong KSL, Zamani B, Paek D, Min Han J, Del Aguila M, Girotra S. Benefits and Risks of Clopidogrel vs. Aspirin Monotherapy after Recent Ischemic Stroke: A Systematic Review and Meta-Analysis. Cardiovasc Ther. 2019 Dec 1;2019:1607181. doi: 10.1155/2019/1607181. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 9, 2024
• First Posted (Actual): August 13, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Egypt; rivaroxaban; dabigatran; cerebral venous thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Embolism and Thrombosis; Intracranial Thrombosis; Intracranial Embolism and Thrombosis; Thromboembolism; Thrombosis; Venous Thrombosis; Sinus Thrombosis, Intracranial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran
• Other Study ID Numbers: 1012019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data supporting this research's findings will be available from the corresponding author, Dr. Mohamed G. Zeinhom, upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes