Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02913326
Recruitment Status : Completed
First Posted : September 23, 2016
Results First Posted : August 15, 2019
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Thromboembolism Drug: Dabigatran etexilate Drug: Warfarin Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RE-SPECT CVT: a Randomised, Open-label, Exploratory Trial With Blinded Endpoint Adjudication (PROBE), Comparing Efficacy and Safety of Oral Dabigatran Etexilate Versus Oral Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis Over a 24-week Period
Actual Study Start Date : December 13, 2016
Actual Primary Completion Date : June 22, 2018
Actual Study Completion Date : June 22, 2018


Arm Intervention/treatment
Experimental: Dabigatran etexilate Drug: Dabigatran etexilate
Active Comparator: Warfarin Drug: Warfarin



Primary Outcome Measures :
  1. 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. [ Time Frame: 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 :
  1. Percentage of Participants With Recurring Cerebral Venous and Dural Sinus Thrombosis; DVT of Any Limb, PE or Splanchnic Vein Thrombosis in Full Observation Period [ Time Frame: 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.

  2. Cerebral Venous Recanalisation as Measured by the Change in Number of Occluded Cerebral Veins and Sinuses at Week 24 [ Time Frame: 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.


  3. Percentage of Participants With Major Bleeding According to ISTH Criteria in Full Observation Period [ Time Frame: 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 bleed

  4. 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 [ Time Frame: 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.

  5. Percentage of Participants With Clinically Relevant Non-major Bleeding Events in Full Observation Period. [ Time Frame: 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.

  6. 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. ]
    Percentage of participants with major bleeding according to ISTH criteria or CRNMBEs after up to 24 weeks.

  7. Percentage of Participants With Any Bleeding Event After up to 24 Weeks [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Written informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations
  • Confirmed diagnosis of Cerebral Venous or dural sinus thrombosis (CVT), with or without intracranial haemorrhage
  • Completion of anticoagulation therapy for 5-15 days which has been administered until randomisation; anticoagulation must include full-dose low molecular weight heparin or unfractionated heparin
  • Eligibility for treatment with an oral anticoagulant
  • Further inclusion criteria apply

Exclusion criteria:

  • Cerebral Venous or dural sinus thrombosis (CVT) associated with central nervous system infection or due to head trauma
  • Planned surgical treatment for CVT
  • Conditions associated with increased risk of bleeding
  • History of symptomatic non-traumatic intracranial haemorrhage with risk of recurrence according to Investigator judgment
  • Treatment with an antithrombotic regimen for an indication other than CVT and requiring continuation of that treatment for the original diagnosis without change in the regimen
  • Severe renal impairment
  • Active liver disease
  • Pregnancy, nursing or planning to become pregnant while in the trial
  • Further exclusion criteria apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02913326


  Hide Study Locations
Locations
Layout table for location information
France
HOP Pellegrin
Bordeaux, France, 33076
HOP Lariboisière
Paris, France, 75475
Germany
Vivantes Netzwerk für Gesundheit GmbH
Berlin, Germany, 12351
Universitätsklinikum Essen AöR
Essen, Germany, 45147
Asklepios Klinik Wandsbek
Hamburg, Germany, 22043
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
Universitätsklinikum Tübingen
Tübingen, Germany, 72076
India
Mazumdar Shaw Medical centre
Bangalore, India, 560099
Nizam's Institute of Medical Sciences
Hyderabad, India, 500082
Caritas Hospital
Kottayam, India, 686630
Magnum Heart Institute
Nashik, India, 422005
All India Institute of Medical Sciences
New Delhi, India, 110029
Sahyadri Speciality Hospital
Pune, India, 411004
Italy
ASST di Cremona
Cremona, Italy, 26100
Fondazione Centro San Raffaele del Monte Tabor
Milano, Italy, 20132
Nuovo Ospedale Civile S. Agostino-Estense
Modena, Italy, 41126
A.O. San Camillo Forlanini
Roma, Italy, 00152
Umberto I Pol. di Roma-Università di Roma La Sapienza
Roma, Italy, 00161
A. O. Ospedale Circolo Fond. Macchi
Varese, Italy, 21100
Netherlands
Academisch Medisch Centrum (AMC)
Amsterdam, Netherlands, 1105 AZ
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584 CX
Poland
University Clinical Center, Gdansk
Gdansk, Poland, 80211
Copernicus Med.Company.Ltd,Hosp.Nicolaus, Gdansk
Gdansk, Poland, 80803
Independent Public Clin.Hospital No.4,Neurol.Dept,Lublin
Lublin, Poland, 20-954
Psychiatry&Neurol.Instit.Interv.Stroke&Cerebrov.Treatm.Cntr
Warsaw, Poland, 02-957
Portugal
Hospital Fernando Fonseca, EPE
Amadora, Portugal, 2720-276
CHLO, EPE - Hospital Egas Moniz
Lisboa, Portugal, 1349-019
CHULN, EPE - Hospital de Santa Maria
Lisboa, Portugal, 1649-035
Centro Hospitalar São João,EPE
Porto, Portugal, 4202-451
Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
Santa Maria da Feira, Portugal, 4520-211
Russian Federation
Reg.State Budget Hlthcare,City Hosp#5,Neurology Dept,Barnaul
Barnaul, Russian Federation, 656045
Interreg. Clinical & Diagnostic Center, Neurol. Dept., Kazan
Kazan, Russian Federation, 420101
St.Petersb,State Hlthcare Instit. Elisabeth Hosp,Neurol.dept
Saint Petersburg, Russian Federation, 195257
Sverdlovsk Reg.Clin.Hosp.No.1
Yekaterinburg, Russian Federation, 620102
Spain
Hospital Ramón y Cajal
Madrid, Spain, 28034
Hospital La Paz
Madrid, Spain, 28046
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Layout table for investigator information
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Study Protocol  [PDF] February 10, 2017
Statistical Analysis Plan  [PDF] March 5, 2018


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02913326     History of Changes
Other Study ID Numbers: 1160.248
2015-004412-38 ( EudraCT Number )
First Posted: September 23, 2016    Key Record Dates
Results First Posted: August 15, 2019
Last Update Posted: August 15, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Sinus Thrombosis, Intracranial
Thrombosis
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Intracranial Thrombosis
Intracranial Embolism and Thrombosis
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Warfarin
Dabigatran
Anticoagulants
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action