Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis
Dutch Heart Foundation
Hôpital Lariboisière, Paris, France

      Background: Endovascular thrombolysis, with or without mechanical clot removal (ET), may be
      beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT), who have a
      poor prognosis despite treatment with heparin. Published experience with ET is promising, but
      only based on case series and not on controlled trials.

      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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