Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial

He, Jiayang; Li, Zhengtu; Huang, Wanyi; Guan, Wenda; Ma, Hongxia; Yang, Zi feng; Wang, Xinhua

Objectives 134 There is empirical evidence that treatment with CLD has positive outcomes against influenza virus 135 infection. Yet, few evidence-based clinical trials have been conducted. We seek to gain an in-depth 136 understanding of the efficacy and safety of CLD use in influenza infections in an evidence-based 137 medicine clinical study. 138 In addition, we will investigate whether CLD granules have different therapeutic effects on 139 different TCM syndrome differentiation by comparing the symptoms before and after treatment. In the follow-up period, specific items will be collected (see online supplementary appendix 1). 154 During the remedial period, participants will be required to register a daily record of symptoms. will be referred to the inclusion and exclusion criteria (shown below). Patients will be enrolled if they 164 meet all inclusion criteria and will not be enrolled if they have any one of the exclusion criteria. 165 Patients will be removed from the trial if they meet one of the rejection criteria or termination 166 standards. The enrolled participants will be required to provide written informed consent, to cooperate 167 with the doctor's treatment, to cooperate with the follow-up and provide information that is not beyond 168 the remit of the ethical approval. Patients that do not comply will be removed from the study. In this 169 period, pharyngeal/throat swabs and blood samples will be collected from participants. The participants 170 will also be distinguished according to TCM syndrome differentiation criteria (described below). 171 The study is designed to enrol 318 patients in six units. and (iv) Have signed a written informed consent from. Exclusion criteria are detailed in Table 2 . 193 If the participants meet rejection criteria, they will be removed, and the data will not be included in 194 the final statistical analysis. However, termination standards relate to enrolled patients that may be 195 terminated during the remedial period and data from these patients will be included in the final 196 statistical analysis. The rejection criteria and termination standards are detailed in Table 3 . Table 4 and are 203 based on the detailed symptoms shown in Table 1 . Patients will be divided into two types according to A doctor will confirm if the patient satisfy the participate criteria after consent being given. 208 Subsequently, it will be discussed with the patient by a medical officer of the trial team. Patients will be 209 given sufficient time (in their own opinion) to fully consider trial entry and to ask questions of 210 investigators. The written informed consent form will be signed by the patient who is willing to 211 participate this clinical trial. If the patient is under the age of 18, his/her parents will be also informed 212 of the details of the trial. Only after both of the child and his/her parent sign the informed consent, the 213 child may participate the trial. 214 A materials consent will be obtained to specifically address the collection of biological samples 215 for future use such as serum and plasma specimens. Blinding 227