LandmarkRCT

TO-ACT

Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis

JAMA Neurology, 2020 · Multicenter, open-label, blinded-end-point randomized trial at 8 hospitals in 3 countries; stopped after the first interim analysis for futility.

Clinical question

Does adding endovascular treatment to standard medical care improve functional outcome in severe cerebral venous thrombosis?

Population: 67 adults with radiologically confirmed CVT and at least one risk factor for a poor outcome: mental status disorder, coma, intracerebral hemorrhage, or thrombosis of the deep venous system.
Inclusion criteria: Radiologically confirmed cerebral venous thrombosis.
At least one poor-prognosis risk factor: mental status disorder, coma, intracerebral hemorrhage or deep venous system thrombosis.
Intervention: Endovascular treatment (mechanical thrombectomy, local intrasinus alteplase or urokinase, or both) within 24 hours of randomization, plus standard medical care (33 patients).
Comparator: Guideline-based standard medical care alone (34 patients).
Primary outcome: Proportion of patients with a good outcome (modified Rankin Scale 0 to 1) at 12 months.
Secondary outcomes: mRS 0 to 1 at 6 months and mRS 0 to 2 at 6 and 12 months.
Ordinal mRS at 12 months, recanalization rate and surgical interventions.
Symptomatic intracranial hemorrhage.
Result: Endovascular treatment did not improve 12-month functional outcome compared with standard care. (mRS 0 to 1 at 12 months 67% vs 68% (relative risk 0.99; 95% CI 0.71–1.38); mortality 12% vs 3% (p = 0.20); symptomatic intracerebral hemorrhage 3% vs 9% (p = 0.61).)

What the trial found

At 12 months, 22 of 33 patients (67%) in the endovascular group and 23 of 34 (68%) in the standard-care group had an mRS of 0 to 1. Mortality was 12% vs 3% and symptomatic intracerebral hemorrhage 3% vs 9%, neither statistically significant.

Current guideline position

The 2024 AHA scientific statement discusses the evidence for endovascular therapy and provides an algorithm for patients who deteriorate or have thrombus propagation despite maximal medical therapy.

Clinical interpretation

TO-ACT does not support routine endovascular treatment in severe CVT; anticoagulation-based care remains the foundation. Because the trial was small and stopped for futility, a benefit in a highly selected group cannot be excluded.

Limitations

Small sample (67 patients) and stopped early for futility.
Open-label design, with blinded end-point assessment.
The trial population was severe CVT; results do not apply to milder disease.

Low certainty

Clinical Context & Relevant Topics (2)

Disease Reference

Acute Ischemic Stroke

Core vs penumbra dynamics, ASPECTS & CT perfusion, Tenecteplase/Alteplase thrombolysis, DAWN/DEFUSE 3 extended thrombectomy, BP targets, and malignant MCA hemicraniectomy.

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Intracranial Hemorrhage: ICH & SAH

Spontaneous ICH vs Aneurysmal SAH, INTERACT-2/ATACH-2 blood pressure targets, emergency anticoagulant reversal, ENRICH minimally invasive evacuation, ISAT coiling, and Nimodipine for delayed cerebral ischemia.

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