Domestic vagus nerve stimulator for the treatment of pharmaco-resistant epilepsy: a prospective, multicenter,randomized,controlled trial

Abstract

Objective To evaluate the efficacy and safety of domestic vagus nerve stimulator for the treatment of pharmaco-resistant epilepsy (PRE) through a prospective, multicenter, randomized, double-blind, parallel controlled trial. Methods A total of 72 patients with PRE in 5 hospitals were enrolled from August 2014 to December 2014. A domestic vagus nerve stimulator was used to conduct vagus nerve stimulation (VNS). All patients with PRE were divided into either a test group (n=35) or a control group (n=37) according to the principle of central randomization. Two weeks after procedure, the vagus nerve stimulator of the test group was turned on really. The parameters (electric current, pulse width, frequency, duration of stimulation, and time interval) of the stimulus set were optimized; whereas that of the control group was turned on simulatedly. At 4 months after operation, the stimulator was turned on and unblinded. According to the Mchugh classification and the modified Engel classification standards, the effectiveness and safety of using the stimulator to treat PRE were evaluated at 4 and 8 months after procedure in both groups. Results At 4 months after procedure, there were 16, 8, 8, 0, and 3 patients, respectively in the McHugh classification grade Ⅰ, Ⅱ, Ⅲ , Ⅳ and Ⅴ test groups, and 9, 3, 16, 0, and 9 patients in the control group, respectively. There were 8, 4, 12, and 11 patients, respectively in the modified Engel classification grade Ⅰ, Ⅱ, Ⅲ , Ⅳ and Ⅴ test groups, and there were 4, 5, 3, and 25 in the control group, respectively. At 4 months after procedure, the seizures in the test groups were improved obviously compared with before procedure. The improvement of the test groups were significantly better than the control group (the improvement rates of seizures were -63.0% and -34.0%, respectively; P=0.006). The symptoms were improved gradually after turning on the stimulator in the control group. At 8 months after procedure, there were 15, 10, 7, 2, and 1 patient, respectively in the Mchugh classification grade Ⅰ, Ⅱ, Ⅲ , Ⅳ, and Ⅴ test groups, and there were 9, 9, 19, 0, and 0 patients in control group, respectively. There were 7, 2, 19, and 9 patients respectively in the modified Engel classification grade Ⅰ, Ⅱ, Ⅲ and Ⅳ test groups, respectively, and there were 4, 2, 12, and 19 patients in the control group, respectively. The efficacy of the control group was gradually similar to the test groups. Compared with the baseline, the efficacy was improved significantly (P<0.001). At 8 months after procedure, the seizure frequency of 33.3% of patients reduced more than 80%, and that of 59.7% of patients reduced more than 50%. Conclusions Using domestic vagus nerve stimulators can significantly reduce the seizure frequency in patients with PRE. It has higher effectiveness and safety. It is suitable for the treatment of patients with PRE. Key words: Vagus nerve stimulation; Multicenter study; Randomized controlled trial; Clinical trial; Pharmaco-resistant epilepsy