A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis (RE-SPECT CVT)
- Registration Number
- NCT02913326
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This is a multi-center, prospective, international, randomized (1:1), open-label study with two parallel groups. This phase III study is planned to investigate the efficacy and safety of dabigatran etexilate versus dose-adjusted warfarin on a net clinical benefit endpoint of major bleeding (ISTH criteria) and new venous thrombotic event (VTE) (primary endpoint) with blinded endpoint adjudication.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dabigatran etexilate Dabigatran etexilate - Warfarin Warfarin -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Composite of Venous Thrombotic Event (VTE) or Major Bleeding Event (MBE) According to International Society on Thrombosis and Haemostasis (ISTH) Criteria in Full Observation Period. From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks. 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
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Clinically Relevant Non-major Bleeding Events in Full Observation Period. From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks. 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.
Percentage of Participants With Major Bleeding According to ISTH Criteria or CRNMBEs After up to 24 Weeks From first administration of trial medication until end of treatment visit, up to 24 weeks. Percentage of participants with major bleeding according to ISTH criteria or CRNMBEs after up to 24 weeks.
Composite Endpoint of Percentage of Participants With New Intracranial Haemorrhage or Worsening of the Haemorrhagic Component of a Previous Lesion After up to 24 Weeks From first administration of trial medication until end of treatment visit, up to 24 weeks. Intracranial haemorrhage (ICH) comprised the subtypes of intracerebral bleeds, subdural bleeds, epidural bleeds and subarachnoid bleeds that were recorded.
Percentage of Participants With Recurring Cerebral Venous and Dural Sinus Thrombosis; DVT of Any Limb, PE or Splanchnic Vein Thrombosis in Full Observation Period From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks. 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.Cerebral Venous Recanalisation as Measured by the Change in Number of Occluded Cerebral Veins and Sinuses at Week 24 Baseline and week 24 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.Percentage of Participants With Major Bleeding According to ISTH Criteria in Full Observation Period From first administration of trial medication until 6 days after last administration of trial medication, up to 25 weeks. 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 bleedPercentage of Participants With Any Bleeding Event After up to 24 Weeks From first administration of trial medication until end of treatment visit, up to 24 weeks. 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.
Trial Locations
- Locations (36)
Caritas Hospital
🇮🇳Kottayam, India
Mazumdar Shaw Medical centre
🇮🇳Bangalore, India
Nizam's Institute of Medical Sciences
🇮🇳Hyderabad, India
Independent Public Clin.Hospital No.4,Neurol.Dept,Lublin
🇵🇱Lublin, Poland
Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
🇵🇹Santa Maria da Feira, Portugal
Magnum Heart Institute
🇮🇳Nashik, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
CHULN, EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
St.Petersb,State Hlthcare Instit. Elisabeth Hosp,Neurol.dept
🇷🇺Saint Petersburg, Russian Federation
Sverdlovsk Reg.Clin.Hosp.No.1
🇷🇺Yekaterinburg, Russian Federation
Reg.State Budget Hlthcare,City Hosp#5,Neurology Dept,Barnaul
🇷🇺Barnaul, Russian Federation
Interreg. Clinical & Diagnostic Center, Neurol. Dept., Kazan
🇷🇺Kazan, Russian Federation
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Nuovo Ospedale Civile S. Agostino-Estense
🇮🇹Modena, Italy
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
HOP Lariboisière
🇫🇷Paris, France
HOP Pellegrin
🇫🇷Bordeaux, France
Asklepios Klinik Wandsbek
🇩🇪Hamburg, Germany
Hospital La Paz
🇪🇸Madrid, Spain
Centro Hospitalar São João,EPE
🇵🇹Porto, Portugal
ASST di Cremona
🇮🇹Cremona, Italy
Vivantes Netzwerk für Gesundheit GmbH
🇩🇪Berlin, Germany
Universitätsklinikum Essen AöR
🇩🇪Essen, Germany
Sahyadri Speciality Hospital
🇮🇳Pune, India
Fondazione Centro San Raffaele del Monte Tabor
🇮🇹Milano, Italy
A. O. Ospedale Circolo Fond. Macchi
🇮🇹Varese, Italy
Umberto I Pol. di Roma-Università di Roma La Sapienza
🇮🇹Roma, Italy
Academisch Medisch Centrum (AMC)
🇳🇱Amsterdam, Netherlands
A.O. San Camillo Forlanini
🇮🇹Roma, Italy
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
University Clinical Center, Gdansk
🇵🇱Gdansk, Poland
Copernicus Med.Company.Ltd,Hosp.Nicolaus, Gdansk
🇵🇱Gdansk, Poland
Psychiatry&Neurol.Instit.Interv.Stroke&Cerebrov.Treatm.Cntr
🇵🇱Warsaw, Poland
Hospital Fernando Fonseca, EPE
🇵🇹Amadora, Portugal
CHLO, EPE - Hospital Egas Moniz
🇵🇹Lisboa, Portugal