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Original Investigation
May 18, 2020

Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial

Author Affiliations
  • 1Department of Neurology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
  • 2Department of Neurology, Hôpital Lariboisière, Paris, France
  • 3Department of Interventional Radiology, XuanWu Hospital, Beijing, China
  • 4Serviço de Neurologia, Instituto de Medicina Molecular, Hospital Santa Maria/Centro Hospitalar Lisboa Norte, Department of Neurosciences and Mental Health, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  • 5Department of Neurology, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
  • 6Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands
  • 7Department of Radiology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
  • 8Department of Neuroradiology, Hôpital Lariboisière, Paris, France
  • 9Clinical Research Unit, Amsterdam University Medical Centers, Amsterdam, the Netherlands
JAMA Neurol. Published online May 18, 2020. doi:10.1001/jamaneurol.2020.1022
Key Points

Question  Does endovascular treatment with guideline-based standard medical care improve the functional outcome of patients with severe cerebral venous thrombosis?

Findings  In this multicenter, open-label, blinded end point randomized clinical trial involving 67 patients with severe cerebral venous thrombosis, no difference in the degree of disability at 12 months was found between patients who underwent endovascular treatment with standard medical care and those who received standard medical care alone.

Meaning  Findings of this study suggest that endovascular treatment may not improve the functional outcome of patients with cerebral venous thrombosis.

Abstract

Importance  To date, only uncontrolled studies have evaluated the efficacy and safety of endovascular treatment (EVT) in patients with cerebral venous thrombosis (CVT), leading to the lack of recommendations on EVT for CVT.

Objective  To evaluate the efficacy and safety of EVT in patients with a severe form of CVT.

Design, Setting, and Participants  TO-ACT (Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis) was a multicenter, open-label, blinded end point, randomized clinical trial conducted in 8 hospitals in 3 countries (the Netherlands, China, and Portugal). Patients were recruited from September 2011 to October 2016, and follow-up began in March 2012 and was completed in December 2017. Adult patients with radiologically confirmed CVT who had at least 1 risk factor for a poor outcome (mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system) were included. Data were analyzed according to the intention-to-treat principle from March 2018 to February 2019. The trial was halted after the first interim analysis for reasons of futility.

Interventions  Patients were randomized to receive either EVT with standard medical care (intervention group) or guideline-based standard medical care only (control group). The EVT consisted of mechanical thrombectomy, local intrasinus application of alteplase or urokinase, or a combination of both strategies. Patients in the intervention group underwent EVT as soon as possible but no later than 24 hours after randomization.

Main Outcomes and Measures  Primary end point was the proportion of patients with a good outcome at 12 months (recovered without a disability; modified Rankin Scale [mRS] score of 0-1). Secondary end points were the proportion of patients with an mRS score of 0 to 1 at 6 months and an mRS score of 0 to 2 at 6 and 12 months, outcome on the mRS across the ordinal continuum at 12 months, recanalization rate, and surgical interventions in relation to CVT. Safety end points included symptomatic intracranial hemorrhage.

Results  Of the 67 patients enrolled and randomized, 33 (49%) were randomized to the intervention group and 34 (51%) were randomized to the control group. Patients in the intervention group vs those in the control group were slightly older (median [interquartile range (IQR)] age, 43 [33-50] years vs 38 [23-48] years) and comprised fewer women (23 women [70%] vs 27 women [79%]). The median (IQR) baseline National Institutes of Health Stroke Scale score was 12 (7-20) in the EVT group and 12 (5-20) in the standard care group. At the 12-month follow-up, 22 intervention patients (67%) had an mRS score of 0 to 1 compared with 23 control patients (68%) (relative risk ratio, 0.99; 95% CI, 0.71-1.38). Mortality was not statistically significantly higher in the EVT group (12% [n = 4] vs 3% [n = 1]; P = .20). The frequency of symptomatic intracerebral hemorrhage was not statistically significantly lower in the intervention group (3% [n = 1] vs 9% [n = 3]; P = .61).

Conclusions and Relevance  The TO-ACT trial showed that EVT with standard medical care did not appear to improve functional outcome of patients with CVT. Given the small sample size, the possibility exists that future studies will demonstrate better recovery rates after EVT for this patient population.

Trial Registration  ClinicalTrials.gov Identifier: NCT01204333.

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