Zhengtian Capsule versus flunarizine in patients with migraine: a multi-center, double-blind, double-dummy, randomized controlled, non-inferior clinical trial.
BACKGROUND
The primary objective of this study was to assess whether Zhengtian Capsule was non-inferior to flunarizine in efficacy and safety profile for prevention of migraine in adults.


METHODS
This was a double-dummy, double-blind, multicenter, positive drug (flunarizine), parallel randomized controlled, non-inferior clinical trial. Patients (n = 360) were randomized in a 1:1 to receive either Zhengtian Capsule or flunarizine, including 12 weeks' intervention and 4 weeks' follow-up. The primary outcome measure was responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period). The secondary outcome measures included migraine attack frequency, the number of migraine days, pain evaluated by visual analogue scale (VAS) score, duration of migraine attacks, the times of using analgesics, patient-reported outcome (PRO) measure of migraine and the scores of short-form 36 Health Survey Scale (SF-36). Weight variation in both groups was also evaluated. Adverse events were monitored throughout the trial.


RESULTS
Zhengtian Capsule was non-inferior to flunarizine in responder rate at week 12 and follow-up period (P = 0.002, P < 0.001). There was fewer migraine days in Zhengtian Capsule group at follow-up period compared with flunarizine (P = 0.001). For the total duration of migraine attacks, there was significant group difference at week 4 which favored the control group (P = 0.009). For the total score of PRO scale, there was statistical difference between the two groups at follow-up period (P = 0.021). There were also group differences between the two groups in the dimensions of somatization symptoms at week 4 (P = 0.022) and functional status at week 12 and follow-up period (P < 0.001, P < 0.001). However, there were no significant differences between the two groups in migraine attack frequency, VAS scores reduction, consumption of acute pain drugs and the dimension scores of SF-36 at any time interval of the treatment period (P > 0.05). No severe adverse events occurred in the trial. Flunarizine was found associated with a weight gain.


CONCLUSIONS
Zhengtian Capsule was non-inferior to flunarizine with regard to the primary endpoint. In addition, it could reduce migraine days and improve the functional status and somatization symptoms of migraine patients with good safety profile.


BACKGROUND
This trial was registered at Chinese Clinical Trial Register (ChiCTR), ChiCTR-TRC-13004412.
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyun Cang, Dong Cheng District, Beijing, China.
Kegang
K
Cao
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyun Cang, Dong Cheng District, Beijing, China.
Fang
F
Han
Department of Neurology, Xiamen Hospital of Traditional Chinese Medicine, No.1739 Xianyue Road, Xiamen, China.
Anji
A
Lin
Department of Neurology, The First Subsidiary Hospital of Anhui College of Traditional Chinese Medicine, No.117 Meishan Road, Hefei, China.
Wenming
W
Yang
Department of Neurology, The Affiliated Hospital to Changchun University of Chinese Medicine, No.1478 Gongnong Avenue, Chaoyang District, Changchun, China.
Jianjun
J
Zhao
Department of Traditional Chinese Medicine, the Central Hospital of Xuhui District, No.966 Huaihai Road, Shanghai, China.
Hui
H
Zhang
Department of Neurology, Hubei Hospital of Traditional Chinese Medicine, No.4 Huayuan Shan, Wu Chang District, Wuhan, China.
Yanbing
Y
Ding
Department of Traditional Chinese Medicine, Nanfang Hospital of Southern Medical University, No.1838 Guangzhou Road north, Guangzhou, China.
Wei
W
Xie
Department of Acupuncture, Beijing Pinggu District Hospital of Traditional Chinese Medicine, No.6 Pingxiang Road, Pinggu district, Beijing, China.
Yinping
Y
Xu
Department of Neurology, the Second Hospital of Jilin University, No.218 Ziqiang Street, Nanguan District, Changchun, China.
Tingmin
T
Yu
Department of Neurology, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, No.19 Renmin Road, Zhengzhou, China.
Xinzhi
X
Wang
Department of Neurology, the Xiangya Hospital Central South University, No.87 Xiangya Road, Changsha, Hunan Province, China.
Xiaosu
X
Yang
Department of Neurology, the First Affiliated Hospital of Chongqing University of Traditional Chinese Medicine, No.1 Youyi Road, Yuanjia Gang, Yuzhong District, Chongqing, China.
Jiying
J
Zhou
Department of Neurology, Zhejiang Hospital of Traditional Chinese Medicine, No.54 Youdian Road, Hangzhou, China.
Qun
Q
Hou
Department of Emergency Medicine, the Third Hospital affiliated with Beijing University of Traditional Chinese Medicine, Beijing, China.
Lihua
L
Yu
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyun Cang, Dong Cheng District, Beijing, China. gaoying973@126.com.
Ying
Y
Gao
D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005444:Flunarizine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D010147:Pain Measurement
D000700:Analgesics; D004365:Drugs, Chinese Herbal; D005444:Flunarizine
Flunarizine; Migraine; Non-inferior; Randomized controlled trial; Zhengtian Capsule