Dataset Information

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

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.

SUBMITTER: Coutinho JM

PROVIDER: S-EPMC7235912 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Cerebral venous sinus thrombosis (CVST) is a rare cause of cerebral infarction. Once patients survive the acute phase, long-term prognosis is generally satisfactory. CVST patients who harbored risk factors known for poor prognosis (e.g., deterioration of consciousness/neurological functions and seizures) were oftentimes unresponsive to systemic heparin treatment. The advantage of combined endovascular mechanical thrombectomy (EMT) and on-site chemical thrombolysis (OCT) plus systemic heparin for CVST over the heparin treatment alone has not been proved. A retrospective study was conducted to analyze consecutive patients with CVST from 2005 to 2015. Patients having clinical improvement or stable disease after heparin treatment were in I/S group; patients having continuous deterioration of consciousness/neurological functions and refractory seizures (despite the use of multiple anti-epileptic drugs) after heparin treatment were in D group. EMT and OCT were indicated for patients in D group. Imaging studies and medical records were reviewed for statistical analysis. Safety issues included new-onset/progression of symptomatic intracerebral hemorrhages (ICH) or procedure-related complications. Total thirty patients were included (I/S group = 16; D group = 14). In D group, the mean time frame from the start of heparin treatment to the endovascular treatment was 3.2 days. Compared with I/S group, all patients in D group had complete stenosis of the sinuses, with higher initial mRS, lower initial GCS, and more seizures (p = 0.006, 0.007, and 0.031, respectively), but no significant differences in the mRS at discharge (p = 0.504). Shorter length of thrombosis and lower initial mRS were associated with better outcomes (p = 0.009 and 0.003, respectively). Thrombosis involving the superior sagittal sinus (SSS) was associated with bad outcomes (p = 0.026). There were two patients (6.7%) with worsening symptomatic ICH, one in each group, managed surgically. The overall mortality of the study was 6.7% (2/30). Combined EMT and OCT after heparin treatment for severe CVST were reasonably safe, which might be considered as a salvage treatment in severe CVST patients who are unresponsive to heparin with heavy clot burden involving SSS in the acute phase. However, further studies are needed to confirm its efficacy and validity.

Project description:ObjectiveTo compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT).MethodsA systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed.ResultsEight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0-2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.39; p < 0.00001). No difference was found for mortality at 90 days and sICH between endovascular therapy and medical management in all analyses and subgroup analyses.ConclusionsThis meta-analysis provides strong evidence that endovascular intervention combined with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO.

Project description:Cerebral venous thrombosis is a rare cause of stroke that poses diagnostic, therapeutic, and prognostic challenges. Mainstay treatment is systemic anticoagulation, but endovascular treatment is increasingly advocated. Our objectives were to describe the epidemiology, treatment, and prognosis of 152 patients with cerebral venous thrombosis. This was a retrospective study of consecutive cerebral venous thrombosis cases from 2006 to 2013 at a comprehensive stroke center through hospital discharge. Predictors of full recovery (modified Rankin Scale scores 0-1) were analyzed with multiple logistic regression and presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs). The population was young (average age: 42 years), majority female (69%), and commonly presenting with cerebral edema (63%), and 72% were transferred in. All patients received systemic anticoagulation; 49% (n=73) required endovascular treatment. Reasons for requiring endovascular treatment included cerebral edema, herniation, or hemorrhagic infarct (n=38); neurologic decline (n=17); rethrombosis, persistent occlusion, or clot propagation (n=10); extensive clot burden (n=7); and persistent headache despite anticoagulation (n=1). There were 7 (10%) procedural complications. Recanalization was successful (61%), partial (30%), and unsuccessful (9%). Overall, 60% fully recovered. Positive predictors of full recovery included hormonal etiology, particularly for patients who were transferred in (AOR: 7.06 [95% CI, 2.27-21.96], interaction P=0.03) and who had migraine history (AOR: 4.87 [95% CI, 1.01-23.50], P=0.05), whereas negative predictors of full recovery were cerebral edema (AOR: 0.11 [95% CI, 0.04-0.34], P<0.001) and motor weakness (AOR: 0.28 [95% CI, 0.09-0.96], P=0.04). As one of the largest cohort studies, our findings suggest that cerebral edema, history of migraine, and hormonal etiology were prognostic and that endovascular treatment might be a safe and effective treatment for cerebral venous thrombosis when conventional management is inadequate.