title: Thrombolysis or anticoagulation for cerebral venous thrombosis: rationale and design of the TO-ACT trial.
abstract: BACKGROUND
  Endovascular thrombolysis, with or without mechanical clot removal, 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 endovascular thrombolysis is promising but only based on case series and not on controlled trials.
  
  
  OBJECTIVE
  The objective of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) trial is to determine if endovascular thrombolysis improves the functional outcome of patients with a severe form of CVT.
  
  
  METHODS
  The TO-A C T trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial. 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 if the responsible physician is uncertain if endovascular thrombolysis or standard anticoagulant treatment is better. One hundred sixty-four patients (82 in each treatment arm) will be included to detect a 50% relative reduction (from 40% to 20%) of poor outcomes.
  
  
  METHODS
  Patients will be randomized to receive either endovascular thrombolysis or standard therapy (therapeutic doses of heparin). Endovascular thrombolysis is composed of local application of rt-plasminogen activator (PA) or urokinase within the thrombosed sinuses, mechanical thrombosuction, or a combination of both. Patients randomized to endovascular thrombolysis will be treated with heparin before and after the interventional procedure, according to international guidelines.
  
  
  RESULTS
  The primary endpoint is the modified Rankin score (mRS) at 12 months, with a score ≥2 defined as poor outcome. Secondary outcomes are six-months mRS, mortality, and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the 'intention-to-treat' principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires.
authors.affiliation: Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Coutinho
authors.forename: José M
authors.initials: JM
authors.lastname: Ferro
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Zuurbier
authors.forename: Marieke S
authors.initials: MS
authors.lastname: Mink
authors.forename: Patrícia
authors.initials: P
authors.lastname: Canhão
authors.forename: Isabelle
authors.initials: I
authors.lastname: Crassard
authors.forename: Charles B
authors.initials: CB
authors.lastname: Majoie
authors.forename: Jim A
authors.initials: JA
authors.lastname: Reekers
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Houdart
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Haan
authors.forename: Marie-Germaine
authors.initials: MG
authors.lastname: Bousser
authors.forename: Jan
authors.initials: J
authors.lastname: Stam
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012851:Sinus Thrombosis, Intracranial / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006493:Heparin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator