A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis (RE-SPECT CVT)

Composite of the percentage of participants with MBE according to ISTH criteria and VTE (recurring cerebral venous thrombosis (CVT); deep venous thrombosis (DVT) of any limb, pulmonary embolism (PE), splanchnic vein thrombosis) in full observation period. All components were adjudicated in a blinded manner. Major bleeds were defined according to the ISTH definition of a major bleed, as follows: * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or * Bleeding associated with a reduction in haemoglobin of at least 2 grams/deciLitre (1.24 millimole/Litre) within 24 h, or leading to transfusion of 2 or more units of blood or packed cells and/or * Fatal bleed

Time frame: From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks.

Population: Full analysis set (FAS): All patients randomised were analysed in the treatment group to which they were randomised regardless of whether they took study medication. This followed the intent-to-treat principle.

Cerebral venous recanalisation was assessed by imaging and was adjudicated. Occlusion of cerebral veins and sinuses was scored as: 1 = full occlusion; 0 = no occlusion/partial occlusion. This score was applied using the below conventions: Superior sagittal, straight, cavernous sinuses, left and right jugular veins each scored individually as either 0 or 1; Right lateral transverse and sigmoid sinus were scored together, Left lateral transverse and sigmoid sinus were scored together, Superior petrous sinus and inferior petrous sinus were scored together; Deep venous system, Superficial cortical veins, Cerebellar veins were scored as systems. For each patient a total score was calculated at baseline and at EOT and the recanalisation score was calculated as EOT - baseline total scores with conventions as 0 = no cerebral veins or sinuses fully occluded and 11 = all cerebral veins and sinuses fully occluded; the lower the score, the better.

Time frame: Baseline and week 24

Population: FAS - Patients with missing/not analysable MRI scan at baseline or end of treatment (EOT) are excluded from the analysis

Intracranial haemorrhage (ICH) comprised the subtypes of intracerebral bleeds, subdural bleeds, epidural bleeds and subarachnoid bleeds that were recorded.

Time frame: From first administration of trial medication until end of treatment visit, up to 24 weeks.

Population: TS - Patients with missing/not analysable MRI scan at baseline or EOT are excluded from the analysis

Percentage of participants with any bleeding event after up to 24 weeks where any bleeding event is the sum of all major and non-major bleeding events.

Time frame: From first administration of trial medication until end of treatment visit, up to 24 weeks.

Population: TS

A clinically relevant non-major bleeding event (CRNMBE) was a clinically overt bleed that did not meet the criteria for a major bleed but prompted a clinical response, in that it led to at least 1 of the following: A hospital admission (i.e. overnight stay in the hospital) for bleeding / A physician guided medical or surgical treatment for bleeding / A physician guided change, interruption or discontinuation of trial medication.

Time frame: From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks.

Population: TS

Major bleeds were defined according to the ISTH definition of a major bleed, as follows: * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or * Bleeding associated with a reduction in haemoglobin of at least 2 grams/deciLitre (1.24 millimole/Litre) within 24 h, or leading to transfusion of 2 or more units of blood or packed cells and/or * Fatal bleed

Time frame: From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks.

Population: TS

Percentage of participants with major bleeding according to ISTH criteria or CRNMBEs after up to 24 weeks.

Time frame: From first administration of trial medication until end of treatment visit, up to 24 weeks.

Population: TS

VTE criterions: * New neurological signs/symptoms or worsening of previous signs/symptoms with new CVT on neuroimaging. * DVT of any limb was documented by: Abnormal compression ultrasonography; An intraluminal filling defect on venography; At autopsy * Splanchnic vein thrombosis: The presence of endoluminal material/absence of flow in the extrahepatic portal veins/mesenteric veins as shown by duplex-Doppler ultrasound/contrast-enhanced CT scan/MRI. * PE was documented by: An intraluminal filling defect in segmental/more proximal branches on spiral CT scan; An intraluminal filling defect/an extension of an existing defect/a sudden cut-off of vessels\>2.5 mm in diameter on the pulmonary angiogram; Perfusion defect of at least 75% of a segment with a local normal ventilation result on ventilation/perfusion lung scan; Inconclusive spiral CT, pulmonary angiography/lung scintigraphy with demonstration of DVT in the lower extremities by compression ultrasonography/venography; At autopsy.

Time frame: From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks.

Population: FAS,~Magnetic resonance imaging (MRI), Computed tomography (CT)