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

In the follow-up period, specific items will be collected (see online supplementary appendix 1). 155 During the remedial period, participants will be required to register a daily record of symptoms. The To ensure the safety of patients, blinding of the study design, data quality and adherence to the 186 study protocol, personnel who participate directly in this study will be adequately trained and 187 follow guidelines for good clinical practice (GCP). Table 2 . 197 If the participants meet rejection criteria, they will be removed, and the data will not be included 198 in the final statistical analysis. However, termination standards relate to enrolled patients that may 199 be terminated during the remedial period and data from these patients will be included in the final 200 statistical analysis. The rejection criteria and termination standards are detailed in Table 3 . Table 4 and 207 are based on the detailed symptoms shown in Table 1 . Patients will be divided into two types 208 according to two TCM practitioners 23 . sufficient time (in their own opinion) to fully consider trial entry and to ask questions of 215 investigators. The written informed consent from will be signed by the patient who is willing to 216 participate this clinical trial. Research doctors will obtain written consent from patients willing to 217 participate in the trial. Additional biological samples will be obtained to be stored for use in future 218 studies. A materials consent will be obtained to specifically address the collection such as serum 219 and plasma specimens. 231 Patients in this group will be administered four bags of CLD granules (3g/per bag) half an hour 232 after a meal, three times daily, for 5 days, taken with an analogous oseltamivir capsule, twice daily, 233 for 5 days. test, all drugs, within the trial period, will be packed by Pan-long-yun-hai Pharmaceutical Company. 246 The drugs will be counted and sorted by a third party (Chinese Evidenced-based Medicine Center, 247 West China Hospital, Sichuan University, China.) . All drugs were within the expiration dates. 248 Other treatments may be taken if the participants have the following symptoms: axillary 249 temperature ≥38.5℃ that lasts for 4 h and does not reduce with physical cooling; body 250 temperature >39℃; or headache or myalgia scores of ≥3 points. 251 Symptomatic treatment measures are as follows. A. Fever: acetaminophen; B. severe cough 252 with white phlegm: Bisolvon; C. mild asthmatic symptoms: long-acting theophylline. No other 253 drugs may be used. Detailed information on drug use will be registered in the CRF. 254 The investigator will instruct the participants to record the actual dose in their patient's diary. 255 Based on this diary, the investigator will evaluate the subject's adherence to the interventions to the 256 following four levels, and record the results on the case report form at each follow-up: 1) Take 257 prescribed medications; 2) Basically prescribed medication (80% to 120% of the dose of the Data entry and management is the responsibility of the assigned data manager who will 270 establish the database and the verification procedure. Then, two specialised trained keyboard 271 operators will input and confirm the data. After checking the CRF, identified entry errors will be 272 corrected until the input data is exactly as the same as the CRF. Any queries on the CRF will be 273 communicated to the researchers through the data query form. These data query