Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis
NCT ID: NCT01204333
Last Updated: 2017-02-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE2/PHASE3
67 participants
INTERVENTIONAL
2011-09-30
2017-10-31
Brief Summary
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Objective: The main objective of the TO-ACT trial is to determine if ET improves the functional outcome of patients with a severe form of CVT
Study design: The TO-ACT trial will be designed as a multi-centre, prospective, randomized, open-label, blinded endpoint (PROBE) trial.
Study population: Patients are eligible if they have a radiologically proven CVT, a high probability of poor outcome (defined by presence of one or more of the following risk factors: mental status disorder, coma, intracranial hemorrhagic lesion or thrombosis of the deep cerebral venous system) and the responsible physician is uncertain if ET or standard anti-coagulant treatment is better.
Intervention: Patients will be randomized to receive either ET or standard therapy (therapeutic doses of heparin). ET consists of local application of alteplase or urokinase within the thrombosed sinuses, and/or mechanical thrombectomy. Glasgow coma score, NIH stroke scale and relevant laboratory parameters will be assessed at baseline.
Endpoints: The primary endpoint is the modified Rankin scale (mRS) at 12 months. The most important secondary outcomes are the mRS, mortality and recanalization rate at 6 months. Major intra- and extracranial hemorrhagic complications within one week following the intervention are the principal safety outcome. Results will be analyzed according to the "intention-to-treat" principle. Assessment of study endpoints will be carried out according to standardized questionnaires by a blinded neurologist or research nurse who is not involved in the treatment of the patient.
Study size: To detect a 50% relative reduction in mRS≥2 (from 40 to 20%), 164 patients (82 in each treatment arm) have to be included (two-sided alpha, 80% power).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Included patients may benefit directly from ET. Complications of ET, most notably intracranial hemorrhages, constitute the most important risk of the study.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Endovascular thrombolysis
Endovascular thrombolysis
Endovascular thrombolysis consists of local application of alteplase or urokinase within the thrombosed sinuses. Standard endovascular techniques to mechanically remove clot material, such as thrombosuction, are allowed, but not mandatory.
Standard treatment
Heparin
The patients randomized to standard care will receive (or continue) either intravenous adjusted dose unfractionated heparin (aPTT value kept within 1.5 to 2.5 times the normal value), or any type of body-weight adjusted low molecular weight heparin in therapeutic dose, according to local custom and international guidelines
Interventions
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Endovascular thrombolysis
Endovascular thrombolysis consists of local application of alteplase or urokinase within the thrombosed sinuses. Standard endovascular techniques to mechanically remove clot material, such as thrombosuction, are allowed, but not mandatory.
Heparin
The patients randomized to standard care will receive (or continue) either intravenous adjusted dose unfractionated heparin (aPTT value kept within 1.5 to 2.5 times the normal value), or any type of body-weight adjusted low molecular weight heparin in therapeutic dose, according to local custom and international guidelines
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Severe form of CVT 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 CVT
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
* Duration from diagnosis to randomization of more than 10 days
* Recurrent CVT
* Any thrombolytic therapy within last 7 days
* Pregnancy (women in the puerperium may be included)
* Isolated cavernous sinus thrombosis
* Isolated intracranial hypertension (without focal neurological signs, with the exception of papilloedema and 6th cranial nerve palsy)
* Cerebellar venous thrombosis with 4th ventricle compression and hydrocephalus, which requires surgery
* Contraindication for anti-coagulant or thrombolytic treatment
1. documented generalized bleeding disorder
2. concurrent thrombocytopenia (\<100 x 10E9/L)
3. documented severe hepatic or renal dysfunction, that interferes with normal coagulation
4. uncontrolled severe hypertension (diastolic \> 120 mm Hg)
5. known recent (\< 3 months) gastrointestinal tract hemorrhage (not including he¬morrhage from rectal hemorrhoids)
* Any known associated condition (such as terminal cancer) with a poor short term (1 year) prognosis independent of CVT
* Clinical and radiological signs of impending transtentorial herniation due to large space-occupying lesions (e.g. large cerebral venous infarcts or hemorrhages)
* Recent (\< 2 weeks) major surgical procedure (does not include lumbar puncture) or severe cranial trauma
* Known allergy against contrast fluid used during endovascular procedures or the thrombolytic drug used in that particular centre
* Previously legally incompetent prior to CVT
* No informed consent
18 Years
ALL
No
Sponsors
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Dutch Heart Foundation
OTHER
Jan Stam, MD, PhD
OTHER
Responsible Party
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Jan Stam, MD, PhD
Prof. Dr. J. Stam
Principal Investigators
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Jan Stam, MD, PhD
Role: STUDY_CHAIR
University of Amsterdam
Jose M Ferro, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital Santa Maria, Lisbon, Portugal
Marie-Germaine Bousser, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hôpital Lariboisière, Paris, France
Patricia Canhão, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital Santa Maria, Lisbon, Portugal
Isabelle Crassard, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hôpital Lariboisière, Paris, France
Charles BL Majoie, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Amsterdam
Jim A Reekers, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Amsterdam
E Houdart, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hôpital Lariboisière, Paris, France
Rob J de Haan, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Amsterdam
Locations
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Centre hospitalier de l'université de Montréal (CHUM)
Montreal, , Canada
XuanWu Hospital
Beijing, , China
Hôpital Lariboisière
Paris, , France
Academic Medical Centre
Amsterdam, , Netherlands
University Medical Centre Groningen
Groningen, , Netherlands
St. Antonius hospital
Nieuwegein, , Netherlands
Erasmus Medical Centre
Rotterdam, , Netherlands
Haga hospital
The Hague, , Netherlands
Medical Centre Haaglanden
The Hague, , Netherlands
Hospital de Braga
Braga, , Portugal
Hospital da Universidade de Coimbra
Coimbra, , Portugal
Hospital Santa Maria
Lisbon, , Portugal
Hospital Sao Jose hospital
Lisbon, , Portugal
Hospital de Santo António
Porto, , Portugal
Inselspital, University Hospital
Bern, , Switzerland
Countries
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References
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Coutinho JM, Stam J. How to treat cerebral venous and sinus thrombosis. J Thromb Haemost. 2010 May;8(5):877-83. doi: 10.1111/j.1538-7836.2010.03799.x. Epub 2010 Feb 9.
Canhao P, Falcao F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis. 2003;15(3):159-66. doi: 10.1159/000068833.
Ciccone A, Canhao P, Falcao F, Ferro JM, Sterzi R. Thrombolysis for cerebral vein and dural sinus thrombosis. Cochrane Database Syst Rev. 2004;2004(1):CD003693. doi: 10.1002/14651858.CD003693.pub2.
Stam J, Majoie CB, van Delden OM, van Lienden KP, Reekers JA. Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: a prospective study. Stroke. 2008 May;39(5):1487-90. doi: 10.1161/STROKEAHA.107.502658. Epub 2008 Mar 13.
Coutinho JM, Zuurbier SM, Bousser MG, Ji X, Canhao P, Roos YB, Crassard I, Nunes AP, Uyttenboogaart M, Chen J, Emmer BJ, Roosendaal SD, Houdart E, Reekers JA, van den Berg R, de Haan RJ, Majoie CB, Ferro JM, Stam J; TO-ACT investigators. Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial. JAMA Neurol. 2020 Aug 1;77(8):966-973. doi: 10.1001/jamaneurol.2020.1022.
Coutinho JM, Ferro JM, Zuurbier SM, Mink MS, Canhao P, Crassard I, Majoie CB, Reekers JA, Houdart E, de Haan RJ, Bousser MG, Stam J. Thrombolysis or anticoagulation for cerebral venous thrombosis: rationale and design of the TO-ACT trial. Int J Stroke. 2013 Feb;8(2):135-40. doi: 10.1111/j.1747-4949.2011.00753.x. Epub 2012 Feb 20.
Other Identifiers
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TOACT
Identifier Type: -
Identifier Source: org_study_id
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