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

• Published in: Brain stimulation Vol. 15; no. 6; pp. 1467 - 1474
• Main Authors: Arsava, Ethem Murat, Topcuoglu, Mehmet Akif, Ay, Ilknur, Ozdemir, Atilla Ozcan, Gungor, Ibrahim Levent, Togay Isikay, Canan, Nazliel, Bijen, Kozak, Hasan Huseyin, Ozturk, Serefnur, Yilmaz, İbrahim Arda, Dora, Babur, Ay, Hakan, Unal, Ali, Ozel, Tugba, Sorgun, Mine Hayriye, Bahadır, Eda Aslanbaba, Peker, Elif, Aykac, Ozlem, Mehdiyev, Zaur, Caglayan, Hale Zeynep Batur, Gurses, Asli Akyol, Pektezel, Mehmet Yasir, Yilmaz, Ezgi, Oge, Dogan Dinc, Parlak, Safak, Bugrul, Ahmet, Ozguner, Hilal, Seker, Aysu Cetiner, Ozdemir, Gokhan, Ongun, Gozde, Yilmaz, Sueda Ecem, Ozguncu, Cihat, Turan Isik, Saziye Melike, Ildiz, Omer Faruk, Mammadli, Azer, Yildogan, Aydin Talip, McClure, Candace
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022; Elsevier
• Subjects: Acute stroke; Cerebral Hemorrhage; Double-Blind Method; Feasibility Studies; Humans; Infarction; Ischemic Stroke; Randomized trial; Safety; Stimulation; Stroke - therapy; Treatment Outcome; Vagus nerve; Vagus Nerve Stimulation - adverse effects; Vagus Nerve Stimulation - methods; Stimulation; Randomized trial; Vagus nerve; Safety; Acute stroke
• ISSN: 1935-861X; 1876-4754
• DOI: 10.1016/j.brs.2022.10.012

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. To assess the safety and feasibility of nVNS for the acute treatment of stroke. 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. 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). 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. •TR-VENUS trial assessed the safety and feasibility of nVNS in patients with acute stroke.•nVNS was not associated with an increased risk of adverse events or unfavorable clinical outcomes.•All participants in whom nVNS was initiated were able to receive all prespecified stimulations.•A non-significant reduction in infarct growth was observed with high-dose nVNS.