An Overview of the Randomized Placebo-Controlled Trials of Chinese Herbal Medicine Formula Granules.

OBJECTIVE: To summarize the characteristics and the outcomes of the Randomized Placebo-Controlled Trials of Chinese Herbal Medicine Granules manufactured by China Resources Sanjiu Pharmaceutical Co., Ltd. METHODS: Databases including China National Knowledge Infrastructure, VIP, Wanfang, PubMed, Cochrane Library, and clinicaltrials.gov were searched in March 2018 for relevant randomized controlled trials (RCTs). Two reviewers independently screened for and selected studies, extracted data, and checked data extraction. Methodological quality was evaluated using the Cochrane Risk of Bias tool. For the outcome, the characteristics of the study, the cure rate, the effectiveness rate, and advert events were described with a method of bibliometrics. Also, we performed meta-analysis only if there were ≥2 studies treated by the same intervention and evaluated by the same outcome. RESULTS: A total of 40 placebo-controlled RCTs treated for 17 diseases were included in our analysis involving 4,632 patients. 16 of 19 studies treated by CHM granules only showed positive result in patients with HBV, HCV, fever, depression, nonalcoholic fatty liver disease, AIDS, and asthma while negative result was shown in patients with migraine. 17 of 21 studies treated by combination therapy against conventional therapy showed positive result in patients with HBV, herpes simplex keratitis, COPD, liver cirrhotic ascites, Parkinson's disease, and diabetic peripheral neuropathy while negative result was shown in patients with myasthenia gravis, angina pectoris, and depression. The pooled result cannot demonstrate that the notifying kidney formula granules had the superior effect with placebo on the clearance of serum HBV DNA and HBeAg in HBV carriers with a RR (and the 95% CI) of 2.97 [0.74,11.91] and 1.99 [0.93,4.29], respectively. But, the CHM granules can reduce within-group HBV DNA levels by more than 2 lgIU/ml; the RR (and 95% CI) was 4.64 [2.89,7.45]. Qizhu granules had a significant effect on clearance of HCV RNA with a RR (and 95% CI) of 6.26 [2.16,18.16]. And, the heat-clearing and detoxifying formula granules were superior to placebo in resolution of cold symptom among patients with fever with a RR and 95% CI of 2.58 [1.40,4.74]. Based on the conventional therapy, the pooled result demonstrated that the Regulating liver formula granules were superior to placebo on the clearance of serum HBeAg in chronic hepatitis B patients with a RR (and the 95% CI) of 1.73 [1.30,2.31]. The EeChen decoction granules were superior to placebo in COPD patients with a RR (and the 95% CI) of 1.13 [1.06,1.22]. 28 of the 40 studies reported adverse events. There were 51 adverse events in CHM formula granules group or combination group (n=2,483) and 26 in control group (n=2,122) totally. Most of the adverse symptoms spontaneously resolved after completing the courses of treatment and the other adverse symptoms improved after symptomatic treatment. CONCLUSION: 16 of 19 studies treated by CHM granules only showed positive result in 7 diseases and negative result in 1 disease. 17 of 21 studies treated by combination therapy against conventional therapy showed positive result in 6 diseases and negative result in 3 diseases. However, both the absolute and relative effectiveness of CHM formula granules compared with placebo need to be considered clinically.

Sini powder () decoction alleviates mood disorder of insomnia by regulating cation-chloride cotransporters in hippocampus.

OBJECTIVE: To investigate the mechanism of Sini Powder () decoction (SND) in the treatment of insomnia. METHODS: The rats were randomly divided into four groups: control, model, SND-treated, and Estazolamtreated groups (n=15 in each group). Sleep deprivation (SD) rat model was established using the modifified multiple platform method for 14 h per day for 14 days, and the behavior of the rats were observed. Na-K-Cl-cotransporter (NKCC1) and K+/Cl- cotransporter (KCC2) in the hippocampus were tested by immunohistochemistry, real-time polymerase chain reaction, and western blot. RESULTS: SD rats displayed anxiety-like behavior, which was alleviated by SND. The protein expressions of NKCC1 and KCC2 in the hippocampus were signifificantly decreased in SD rats compared with those in control rats (P<0.05); these proteins were signifificantly increased by SND (P<0.05). The mRNA expression of KCC2 was signifificantly decreased in SD rats (0.62±0.35 vs. 2.29±0.56; P=0.044), while SND showed a tendency to increase the mRNA of KCC2 in SD rats (P>0.05). By contrast, the mRNA expression of NKCC1 was signifificantly increased in the hippocampus of SD rats (6.58±1.54 vs. 2.82±0.32; P=0.011), while SND decreased the mRNA expression of NKCC1 (6.58±1.54 vs. 2.79±0.81; P=0.016). CONCLUSIONS: Chinese medicine SND could alleviate mood disorder of SD rats by regulating cation-chloride cotransporters, such as NKCC1 and KCC2. These fifindings would have major implications in the mechanism of SND to relieve insomnia.

Traditional Chinese medicine for chronic fatigue syndrome: a systematic review of randomized clinical trials.

BACKGROUND: There is no curative treatment for chronic fatigue syndrome (CFS). Traditional Chinese medicine (TCM) is widely used in the treatment of CFS in China. OBJECTIVE: To evaluate the effectiveness and safety of TCM for CFS. METHODS: The protocol of this review is registered at PROSPERO. We searched six main databases for randomized clinical trials (RCTs) on TCM for CFS from their inception to September 2013. The Cochrane risk of bias tool was used to assess the methodological quality. We used RevMan 5.1 to synthesize the results. RESULTS: 23 RCTs involving 1776 participants were identified. The risk of bias of the included studies was high. The types of TCM interventions varied, including Chinese herbal medicine, acupuncture, qigong, moxibustion, and acupoint application. The results of meta-analyses and several individual studies showed that TCM alone or in combination with other interventions significantly alleviated fatigue symptoms as measured by Chalder's fatigue scale, fatigue severity scale, fatigue assessment instrument by Joseph E. Schwartz, Bell's fatigue scale, and guiding principle of clinical research on new drugs of TCM for fatigue symptom. There was no enough evidence that TCM could improve the quality of life for CFS patients. The included studies did not report serious adverse events. CONCLUSIONS: TCM appears to be effective to alleviate the fatigue symptom for people with CFS. However, due to the high risk of bias of the included studies, larger, well-designed studies are needed to confirm the potential benefit in the future.

Prospective registration, bias risk and outcome-reporting bias in randomised clinical trials of traditional Chinese medicine: an empirical methodological study.

BACKGROUND: Clinical trials on Traditional Chinese Medicine (TCM) should be registered in a publicly accessible international trial register and report on all outcomes. We systematically assessed and evaluated TCM trials in registries with their subsequent publications. OBJECTIVE: To describe the characteristics of TCM trials, estimate bias risk and outcome-reporting bias in clinical trials. DATA SOURCES AND STUDY SELECTION: Fifteen trial registries were searched from their inception to July 2012 to identify randomised trials on TCM including Chinese herbs, acupuncture and/or moxibustion, cupping, tuina, qigong, etc. DATA EXTRACTION: We extracted data including TCM specialty and treated disease/conditions from the registries and searched for subsequent publications in PubMed and Chinese databases. We compared information in the registries of completed trials with any publications focusing on study design, sample size, randomisation, bias risk including reporting bias from the register protocol. RESULTS: 1096 registered randomised trials were identified evaluating TCM, of which 505 were completed studies (46.1%). The most frequent conditions were pain (13.3%), musculoskeletal (11.7%), nervous (8.7%), digestive (7.1%), circulatory (6.5%), respiratory (6.3%), mental and behavioural disorders (6.2%) and cancer (6.0%). The trial register data identified parallel, phase II/III randomised trials with sample size estimations and blinding, but limited information about randomisation (sequence generation and allocation concealment). Comparing trial registration data of 115 completed trials (22.8%) with their subsequent 136 publications, inconsistencies were identified in one or more of the following: sample size (11%), outcome assessor blinding (37.5%), primary outcomes (29%) and safety (28%) reporting. CONCLUSIONS: Increasing numbers of clinical trials investigating a variety of TCM interventions have been registered in international trial registries. The study design of registered TCM trials has improved in estimating sample size, use of blinding and placebos. However, selective outcome reporting is widespread and similar to conventional medicine and therefore study conclusions should be interpreted with caution.

Chinese herbal medicine for gout: a systematic review of randomized clinical trials.

Patients with gout referring to Chinese herbal medicine are not rare in China, and a great number of clinical trials on herbal medicine have been published. However, there has not been a systematic review to summarize the evidence of Chinese herbal medicine for gout. The aim of this study is to evaluate the evidence for the effectiveness and safety of Chinese herbal medicine for gout. We searched for randomized clinical trials on Chinese herbal medicine for gout till December 2012. Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.2 was used to synthesize the results. We included 57 trials involving 4,527 gout patients. The quality of trials was generally poor. No trial reported health-related quality of life in patients. There is not enough evidence showing that herbal medicine was statistically more effective than conventional medications in pain relief [mean difference (MD), -0.03; 95% confidence interval (CI), -0.06, 0.00], but herbal medicine combined with conventional medicines may have better effectiveness (MD, -0.33; 95% CI, -0.59, -0.07). Trials that reported function limitation relief found herbal medicine more effective than conventional medications (MD, -0.23; 95% CI, -0.32, -0.15). There was no evidence showing that herbal medicine prevents gout recurrence better. Twenty-five out of 41 trials, involving 23 different herbal prescriptions, found statistical significance in lowering serum uric acid level, and the overall effect from Chinese herbal medicine in inflammation relief is better than conventional therapies in 19 trials with 17 different prescriptions. The current data show that herbal medicine leads to fewer side reactions compared to conventional therapies [risk ratio (RR), 0.11; 95% CI, 0.08 to 0.15]. Chinese herbal medicine may have clinical effectiveness for functional recovery in patients with gout, and lead to a safe control of serum uric acid level and inflammation severity. Due to low quality of trials, trials with higher methodological quality and less heterogeneity are needed in the future.

[Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes].

BACKGROUND: Randomized controlled trial (RCT) is considered as the gold standard for the efficacy assessment of medicines. With the increasing number of Chinese patent drugs for treatment of type 2 diabetes, the methodology of post-marketing RCTs evaluating the efficacy and specific effect has become more important. OBJECTIVE: To investigate post-marketing Chinese patent drugs for treatment of type 2 diabetes, as well as the methodological quality of post-marketing RCTs. SEARCH STRATEGY: Literature was searched from the books of Newly Compiled Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the State Food and Drug Administration and the Ministry of Human Resources and Social Security of the People's Republic of China, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period for searching ran from the commencement of each database to August 2011. INCLUSION CRITERIA: RCTs of post-marketing Chinese patent drugs for treatment of type 2 diabetes with intervention course no less than 3 months. DATA EXTRACTION AND ANALYSIS: Two authors independently evaluated the research quality of the RCTs by the checklist of risk bias assessment and the data collection forms based on the CONSORT Statement. Independent double data-extraction was performed. RESULTS: The authors identified a total of 149 Chinese patent drugs for treatment of type 2 diabetes. According to different indicative syndromes, the Chinese patent drugs can be divided into the following types, namely, yin deficiency and interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41 RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor endpoint outcome reports were found. Risk bias analysis showed that 81% of the included studies reported randomization for grouping without sequence generation, 98% of these studies did not report concealment of random numbers, 5% used placebo, 10% reported outcome attrition bias and no study employed the analysis of intention-to-treat and 98% reported the diagnostic criteria for type 2 diabetes. The participants mainly consisted of outpatients without complications (76%). The minimum and maximum sample size was 40 and 300 (106 ± 60), respectively. CONCLUSION: The inclusion and exclusion criteria and outcome measures did not match the purposes and contents of post-marketing research in the included studies. They also failed to reflect the basic principles of traditional Chinese medicine in the process of diagnosis and treatment. The demographic characteristics of the patients, the indications for medicine and the syndrome differentiation process were not reported sufficiently and transparently. In order to improve the post-marketing research and promote the rational use of Chinese patent drugs, it is recommended that phase IV clinical trials should establish clear research purpose as well as hypothesis first, and choose scientific and evidence-based study design and outcome measures. In addition, guidelines for implementation of post-marketing research should be developed.