Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke
Ethem Murat Arsava, Mehmet Akif Topçuoğlu, İlknur Ay, Atilla Özcan Özdemir, İbrahim Levent Güngör, Canan Togay Işıkay, Bijen Nazlıel, Hasan Hüseyin Kozak, Şerefnur Öztürk, İbrahim Arda Yilmaz, Babür Dora, Hakan Ay, Ali Unal, Tugba Ozel, Mine Hayriye Sorgun, Eda Aslanbaba Bahadır, Elif Peker, Ozlem Aykac, Zaur Mehdiyev, Hale Zeynep Batur Caglayan, Asli Akyol Gurses, Mehmet Yasir Pektezel, Ezgi Yilmaz, Dogan Dinc Oge, Safak Parlak, Ahmet Bugrul, Hilal Ozguner, Aysu Cetiner Seker, Gokhan Ozdemir, Gozde Ongun, Sueda Ecem Yilmaz, Cihat Ozguncu, Saziye Melike Turan Isik, Omer Faruk Ildiz, Azer Mammadli, Aydin Talip Yildogan, Candace McClure
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.