The Role of Factor XIII Activation Peptide and D-dimer Values for the Diagnosis of Cerebral Venous Thrombosis (CVT)

NCT ID: NCT00924859

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 401 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2017-12-31

Brief Summary

The investigators aim to assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test, to exclude CVT in patients with clinical suspicion of CVT.

Detailed Description

Background

Because of the broad clinical spectrum it is often difficult to establish the diagnosis of cerebral venous thrombosis (CVT). Combined MRI/MRV and contrast-enhanced CT are the most accurate methods for diagnosis of CVT. However these methods are often not available on an emergency basis. This stresses the need for additional widely available tests such as coagulation markers to exclude CVT. The diagnostic value of D-dimer levels for the exclusion of CVT is still under debate. Other potential coagulation markers have not been systematically investigated. The investigators aim to assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test, to exclude CVT in patients with clinical suspicion of CVT. Consecutive patients with clinical suspicion of CVT at the emergency department of the University Hospital Bern will be included in this study over a two year period. All included patients will receive standard care applied by the treating physician who will follow international recommendations. Patient involvement in the study shall not influence any treatment decision. On admission patients will undergo a complete diagnostic work-up, including a clinical neurological examination, standard laboratory examination including D-dimer values, and brain contrast CT and/or MRI/MRV. In addition, plasma FXIII-AP will be analyzed. FXIII-AP will be analyzed at the Hemostasis Research Laboratory, Department of Hematology, University of Bern, based on a newly developed highly sensitive and specific ELISA method. The investigators will be blinded for the clinical symptoms and diagnosis of the patient. The study will be conducted according to the guidelines of the STARD (Standards for Reporting Diagnostic Accuracy) initiative.

The following primary evaluation criteria will be analysed:1) The overall diagnostic accuracy of FXIII-AP to exclude CVT in patients with clinical suspicion of CVT; 2) The overall diagnostic accuracy of D-dimer to exclude CVT in patients with clinical suspicion of CVT; 3) Roc curves will be calculated.

Prespecified subgroup analyses will be performed according to the clinical presentation: 1) isolated headache; 2) isolated intracranial hypertension (headache and papilledema); 3) Focal neurological deficits and/or seizures and/or disturbances of consciousness. Furthermore, prespecified subgroup analyses will be performed according to modes of onset: 1) acute (symptoms < 48 hours duration); 2) subacute (symptoms > 48 hours and < 7 days duration); 3) chronic (symptoms > 7 days duration).

The following secondary evaluation criteria will be assessed: 1) The overall frequency of CVT in patients with clinical suspicion of CVT; 2) The overall frequency of other diseases in patients with clinical suspicion of CVT; 3) The site of involved veins and sinus in patients with CVT.

Objective

The investigators aim to assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test, to exclude CVT in patients with clinical suspicion of CVT.

Methods

Consecutive patients with clinical suspicion of CVT at the emergency department of the University Hospital Bern will be included in this study over a two year period. All included patients will receive standard care applied by the treating physician who will follow international recommendations. D-dimer measurement at entry will be performed using a rapid sensitive assay. FXIII-AP will be analyzed at the Hemostasis Research Laboratory, Department of Hematology, University of Bern based on a highly sensitive and specific ELISA method.The investigators will be blinded for the clinical symptoms and diagnosis of the patient.

Conditions

Cerebral Venous Thrombosis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

1

Patients with clinical suspicion of CVT

ELISA Test

Intervention Type: OTHER

assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test

Interventions

ELISA Test

assess the overall accuracy of D-dimer values and FXIII activation peptide (FXIII-AP), using a newly developed ELISA test

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adults with clinical suspicion of CVT
• Isolated unexplained headache of less than 30 days duration
• Headache associated with focal central neurological deficits of less than 30 days duration
• Headache associated with disturbed consciousness of less than 30 days duration
• Headache associated with epileptic seizures of less than 30 days duration
• Unexplained papilledema of less than 30 days duration

Exclusion Criteria

• Deep venous thrombosis within 3 months prior to admission
• Pulmonary embolism within 3 months prior to admission
• Ischemic stroke within 3 months prior to admission
• Myocardial infarction within 3 months prior to admission
• Other vascular disease within 3 months prior to admission
• Headache due to trauma
• Malignant neoplasia
• Treatment with anticoagulants prior to admission

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schweizerische Herzstiftung

OTHER

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Inselspital Bern, Universitiy Hospital

Principal Investigators

Marcel Arnold, MD Prof.

Role: PRINCIPAL_INVESTIGATOR

Dep. of Neurology, Bern University Hospital

Locations

Department of Neurology, Academic Medical Centre, University of Amsterdam

Amsterdam, , Netherlands

Dep. of Neurology, Bern University Hospital

Bern, , Switzerland

Countries

Netherlands; Switzerland

References

Heldner MR, Zuurbier SM, Li B, Von Martial R, Meijers JCM, Zimmermann R, Volbers B, Jung S, El-Koussy M, Fischer U, Kohler HP, Schroeder V, Coutinho JM, Arnold M. Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels. Neurology. 2020 Aug 18;95(7):e898-e909. doi: 10.1212/WNL.0000000000009998. Epub 2020 Jun 23.

Reference Type: DERIVED

PMID: 32576633 (View on PubMed)

Other Identifiers

112/09

Identifier Type: -

Identifier Source: org_study_id