The Efficacy and Safety of Batroxobin Combined With Anticoagulation in Cerebral Venous Sinus Thrombosis

Our previous clinical case observations showed that batroxobin combined with anticoagulation therapy can improve the sinus recanalization rate in patients with CVST, shorten the hospital stay, and increase the neurological score of patients. Its main mechanism is to inhibit thrombosis after reducing fibrinogen, and to dissolve thrombus.

To further explore the safety of batroxobin combined with anticoagulation therapy for CVST, an open-label, randomized controlled (1: 1), single-center, prospective study was used. Further study on the safety and effectiveness of batroxobin combined with anticoagulation for CVST.

Study Overview

• Status: Unknown
• Conditions: Cerebral Venous Sinus Thrombosis; Batroxobin
• Intervention / Treatment: Drug: Batroxobin combined with low molecular weight heparin

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ran Meng, Ph.D; Phone Number: +861083199280 +86-10-83199280; Email: ranmeng2011@pku.org.cn
• Study Contact Backup: Name: Zhiying Chen, M.S.; Phone Number: +861083199280 +86-10-83199280; Email: chenzhiying@ccmu.edu.cn

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Captial Medical University
    • Contact: Ran Meng, Ph.D; Phone Number: +86-10-83199280; Email: ranmeng2011@pku.org.cn
    • Contact: Zhiying Chen, M.S.; Phone Number: +86-10-83199280; Email: chenzhiying@ccmu.edu.cn
    • Principal Investigator: Zhiying Chen
    • Principal Investigator: Jiayue Ding
    • Principal Investigator: Da Zhou
    • Principal Investigator: Chaobo Bai
    • Principal Investigator: Jingyuan Ya
    • Principal Investigator: Kexin Jin
    • Principal Investigator: Zhongao Wang
    • Principal Investigator: Jingwei Guan
    • Principal Investigator: Jingkun Sun
    • Principal Investigator: Siying Song

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Cerebral venous thrombosis, confirmed by cerebral angiography (with intra-arterial contrast injection), magnetic resonance venography or computed tomographic venography.

2. Severe form of CVST with a high chance of incomplete recovery, as defined by the presence of one or more of the following risk factors

   1. Intracerebral hemorrhagic lesion due to CVST
   2. Mental status disorder
   3. Coma (Glasgow coma scale < 9)
   4. Thrombosis of the deep cerebral venous system
3. Uncertainty by the treating physician if ET or standard heparin therapy is the optimal therapy for the patient.

Exclusion Criteria:

1. Conditions associated with increased risk of bleeding
2. Any thrombolytic therapy within last 7 days
3. Cerebellar venous thrombosis with 4th ventricle compression and hydrocephalus, which requires surgery
4. Contraindication for anti-coagulant or batroxobin treatment 1)documented generalized bleeding disorder 2)concurrent thrombocytopenia (<100 x 10E9/L) 3)Fibrinogen below 100mg /dl 4)documented severe hepatic or renal dysfunction, that interferes with normal coagulation 5)uncontrolled severe hypertension (diastolic > 120 mm Hg) 6)known recent (< 3 months) gastrointestinal tract hemorrhage (not including hemorrhage from rectal hemorrhoids)
5. Any known associated condition (such as terminal cancer) with a poor short term (1 year) prognosis independent of CVST
6. Clinical and radiological signs of impending transtentorial herniation due to large space-occupying lesions (e.g. large cerebral venous infarcts or hemorrhages)
7. Recent (< 2 weeks) major surgical procedure (does not include lumbar puncture) or severe cranial trauma
8. Previously legally incompetent prior to CVST
9. Severe renal impairment
10. Active liver disease
11. Pregnancy, nursing or planning to become pregnant while in the trial
12. Further exclusion criteria apply
13. No informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Batroxobin combined with low molecular weight heparin; Standard treatment of Batroxobin combined with low molecular weight heparin.	Drug: Batroxobin combined with low molecular weight heparin; Standard treatment of Batroxobin combined with low molecular weight heparin
OTHER: Low-molecular-weight heparin therapy; Low-molecular-weight heparin combined with routine drug therapy.	Drug: Batroxobin combined with low molecular weight heparin; Standard treatment of Batroxobin combined with low molecular weight heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Major Bleeding Event (MBE) According to International Society on Thrombosis and Haemostasis (ISTH) Criteria in Full Observation Period	2 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Favorable clinical outcome	modified Rankin score 0-1	3 months after randomization
Recanalization rate of cerebral venous system	DSA or MRV confirms cerebral venous sinus flow	3 months after randomization
Required surgical intervention in relation to CVST		3 months after randomization
All cause mortality		3 months after randomization

Collaborators and Investigators

• Sponsor: Capital Medical University

Publications and helpful links

General Publications

• Ding J, Zhou D, Hu Y, Elmadhoun O, Pan L, Ya J, Geng T, Wang Z, Ding Y, Ji X, Meng R. The efficacy and safety of Batroxobin in combination with anticoagulation on cerebral venous sinus thrombosis. J Thromb Thrombolysis. 2018 Oct;46(3):371-378. doi: 10.1007/s11239-018-1718-y.
• Ding JY, Pan LQ, Hu YY, Rajah GB, Zhou D, Bai CB, Ya JY, Wang ZA, Jin KX, Guan JW, Ding YC, Ji XM, Meng R. Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience. CNS Neurosci Ther. 2019 May;25(5):638-646. doi: 10.1111/cns.13093. Epub 2019 Jan 23.
• Yang Q, Duan J, Fan Z, Qu X, Xie Y, Nguyen C, Du X, Bi X, Li K, Ji X, Li D. Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black-Blood Thrombus Imaging. Stroke. 2016 Feb;47(2):404-9. doi: 10.1161/STROKEAHA.115.011369. Epub 2015 Dec 15. Erratum In: Stroke. 2016 Feb;47(2):e39.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2020
• Primary Completion (ANTICIPATED): March 1, 2021
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (ACTUAL): February 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cerebral Venous Sinus 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; Sinus Thrombosis, Intracranial; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Hemostatics; Coagulants; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Batroxobin
• Other Study ID Numbers: CVST2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No