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Randomized Controlled Trial
. 2022 Nov-Dec;15(6):1467-1474.
doi: 10.1016/j.brs.2022.10.012. Epub 2022 Nov 7.

Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke

Ethem Murat Arsava  1 , Mehmet Akif Topcuoglu  2 , Ilknur Ay  3 , Atilla Ozcan Ozdemir  4 , Ibrahim Levent Gungor  5 , Canan Togay Isikay  6 , Bijen Nazliel  7 , Hasan Huseyin Kozak  8 , Serefnur Ozturk  9 , İbrahim Arda Yilmaz  10 , Babur Dora  11 , Hakan Ay  3 ; TR-VENUS investigators
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Free article
Randomized Controlled Trial

Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke

Ethem Murat Arsava et al. Brain Stimul. 2022 Nov-Dec.
Free article

Abstract

Background: Non-invasive vagus nerve stimulation (nVNS) using a hand-held stimulator placed on the neck is an FDA-approved treatment for primary headache disorders. The safety of nVNS is unknown in stroke patients.

Objective: To assess the safety and feasibility of nVNS for the acute treatment of stroke.

Methods: TR-VENUS (clinicaltrials.gov identifier NCT03733431) was a randomized, sham-controlled, open-label, multicenter trial conducted in patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH). Patients were randomly assigned to standard-dose nVNS, high-dose nVNS, or sham stimulation. The primary endpoint was a composite safety outcome defined as bradycardia or reduction in mean arterial blood pressure during treatment or progression of neurological or death within 24 h of treatment. The feasibility endpoints were the proportion of eligible subjects receiving nVNS within 6 h of symptom onset and the proportion completing all pre-specified treatment doses. Efficacy assessments included infarct growth from baseline to 24 h after treatment.

Results: Sixty-nine patients (61 IS, 8 ICH) completed the study. The composite safety outcome was achieved in 32.0% in sham and 47.7% in nVNS group (p = 0.203). Treatment was initiated in all but two randomized patients. All dosed subjects received 100% of prespecified stimulations. A non-significant reduction in infarct growth was observed in the high-dose nVNS group (184.2% in sham vs. 63.3% in high-dose nVNS; p = 0.109).

Conclusions: The results of this study suggest that nVNS may be safe and feasible in the setting of acute stroke. These findings support further development of nVNS as a potential treatment for acute ischemic stroke.

Keywords: Acute stroke; Randomized trial; Safety; Stimulation; Vagus nerve.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ethem Murat Arsava Dr Arsava receives honoraria from Fresenius Kabi, Bayer AG, Daiichi-Sankyo, Pfizer, Sanofi, Abbott, and Nutricia. He serves on the advisory boards of Abbott, Daiichi-Sankyo, Bayer AG, Pfizer, Fresenius Kabi, and Nutricia. Mehmet Akif Topcuoglu Dr Topcuoglu receives honoraria from Fresenius Kabi, Daiichi-Sankyo, Sanofi, and Abbott. He serves on the advisory boards for Abbott, Fresenius Kabi, Daiichi-Sankyo, and Pfizer. Hakan Ay Hakan Ay is an employee of Takeda Pharmaceutical Company and holds an academic appointment at the Massachusetts General Hospital, Harvard Medical School. The remaining authors declare no conflict of interest.

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