Clinical Trial: Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TOACT)

Brief Summary:

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 &quo

Detailed Summary:
Sponsor: Jan Stam, MD, PhD

Current Primary Outcome: Favorable clinical outcome (modified Rankin score 0-1) [ Time Frame: 12 months after randomization ]

Outcome on the modified Rankin Scale (mortality included) at 12 months after randomization is considered the primary study outcome to determine the efficacy of thrombolytic treatment. For the primary endpoint the mRS will be dichotomized between 1 and 2 (i.e. incomplete recovery is defined as a score of 2 or higher, including death).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Favorable clinical outcome (modified Rankin score 0-1) [ Time Frame: 6 months after randomization ]
  • Recanalization rate of cerebral venous system [ Time Frame: 6 months ]
  • All cause mortality [ Time Frame: 6 months ]
  • Required surgical intervention in relation to CVT [ Time Frame: 6 months ]
    The proportion of surgical intervention that are required in relation to cerebral venous thrombosis (e.g. ventricular shunting procedures or craniotomy)
  • Major extracranial and symptomatic intracranial hemorrhagic complications [ Time Frame: 1 week after randomization ]
    Extracranial hemorrhage is classified as major if clinically overt and associated with fall in hemoglobin of 1.2 mmol/l (2 gram/dl) or more within 48 hours, if it is retroperitoneal, intracranial or intraocular, or requires a transfusion of two or more units of packed cells. Any bleeding requiring operation or leading to death is regarded as major. Symptomatic intracranial hemorrhage is defined as any apparently extravascular blood in the brain associated with an increase of 4 points or more on the NIHSS score, or leading to death.
  • Dead or dependency (modified Rankin score 3-6) [ Time Frame: 6 and 12 months ]
  • Modified Rankin Scale at 1 month after randomization [ Time Frame: 1 month after randomization ]


Original Secondary Outcome:

  • Favorable clinical outcome (modified Rankin score 0-1) [ Time Frame: 6 months after randomization ]
  • Recanalization rate of cerebral venous system [ Time Frame: 6 months ]
  • All cause mortality [ Time Frame: 6 months ]
  • Required surgical intervention in relation to CVT [ Time Frame: 6 months ]
    The proportion of surgical intervention that are required in relation to cerebral venous thrombosis (e.g. ventricular shunting procedures or craniotomy)
  • Major extracranial and symptomatic intracranial hemorrhagic complications [ Time Frame: 1 week after randomization ]
    Extracranial hemorrhage is classified as major if clinically overt and associated with fall in hemoglobin of 1.2 mmol/l (2 gram/dl) or more within 48 hours, if it is retroperitoneal, intracranial or intraocular, or requires a transfusion of two or more units of packed cells. Any bleeding requiring operation or leading to death is regarded as major. Symptomatic intracranial hemorrhage is defined as any apparently extravascular blood in the brain associated with an increase of 4 points or more on the NIHSS score, or leading to death.
  • Dead or dependency (modified Rankin score 3-6) [ Time Frame: 6 and 12 months ]


Information By: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Dates:
Date Received: September 15, 2010
Date Started: September 2011
Date Completion: October 2017
Last Updated: February 11, 2017
Last Verified: November 2016