Effects of Qingda granule on patients with grade 1 hypertension at low-medium risk: study protocol for a randomized, controlled, double-blind clinical trial.

BACKGROUND: Numerous pre-clinical studies showed that Qingda granule (QDG) was effective in treating hypertension. This study aims to evaluate the efficacy and safety of QDG in reducing blood pressure among patients with grade 1 hypertension at low-medium risk. METHODS: The study is designed as a randomized, multi-center, double-blinded, non-inferiority clinical trial. Five hundred fifty-two patients with grade 1 hypertension at low-medium risk from 13 hospitals will be recruited and randomly assigned to the QDG group (n = 276, treated with valsartan capsule simulation agent and QDG) or control group (n = 276, treated with valsartan capsule and QDG simulation agent). The treatment period will be 4 weeks and the follow-up period will last 4 weeks after treatment. Primary outcome will be a decreased value of systolic blood pressure and diastolic blood pressure after treatment. And second outcome will include the decreased value of diastolic blood pressure and systolic blood pressure at the end of follow-up, the percentage of participants achieving normal blood pressure at the end of treatment and follow-up, the Hamilton Anxiety Scale and TCM syndrome scores at the end of treatment and follow-up, and levels of hypertensive hormones at end of treatment and follow-up. DISCUSSION: This study will provide initial evidence regarding the clinical efficacy and safety of QDG in treating grade 1 hypertension at low-medium risk. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033890 . Registered on 15 June 2020.

[Evidence mapping of clinical research on traditional Chinese medicine in treatment of diabetic foot].

The present study comprehensively summarized the clinical randomized controlled trials(RCTs) and systematic reviews/Meta-analyses of traditional Chinese medicine(TCM) in the treatment of diabetic foot by evidence mapping and clarified the distribution of evidence in this field.CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for clinical RCTs and systematic reviews on TCM in the treatment of diabetic foot published in the past ten years.The evidence was analyzed and displayed in the form of text combined with figures and tables.AMSTAR was used for the quality evaluation of systematic reviews.A total of 1 037 clinical RCTs and 20 systematic reviews/Meta-analyses were included.The overall publishing trend was stable, and the scale of RCTs was small.TCM interventions for diabetic foot mainly included external application and foot bath.Much attention was paid to the outcome indicators including total effective rate, ankle brachial index(ABI), and TCM syndromes, while less attention to neuropathy scores, emotional psychology, and long-term prognosis.The overall quality of systematic reviews was low, and the majority of studies indicated that TCM had potential efficacy in treating diabetic foot, and there was still a lack of clear clinical evidence of efficacy.TCM has both advantages and problems in the treatment of diabetic foot.At present, there is still a lack of high-quality research, suggesting that more large-sample, multi-center RCTs should be launched in the future, and the quality of related systematic reviews/Meta-analyses should be improved to fully explore and give full play to the advantages of TCM in the treatment of diabetic foot, and promote the development of the clinical and evidence-based medicine of TCM in the treatment of diabetic foot.

The clinical population pharmacokinetics, metabolomics and therapeutic analysis of alkaloids from Alstonia scholaris leaves in acute bronchitis patients.

BACKGROUND: Capsule of alkaloids from leaf of Alstonia scholaris (CALAS) is a new investigational botanical drug (No. 2011L01436) for respiratory disease. Clinical population pharmacokinetics (PK), metabolomics and therapeutic data are essential to guide dosing in patients. Previous research has demonstrated the potential therapeutic effect of CALAS on acute bronchitis. Further clinical trial data are needed to verify its clinical efficacy, pharmacokinetics behavior, and influence of dosage and other factors. PURPOSE: To verify the clinical efficacy and explore the potential biomarkers related to CALAS treatment for acute bronchitis. MATERIALS AND METHODS: Oral CALAS was assessed in a randomized, double-blind, placebo-controlled trial. Fifty-five eligible patients were randomly assigned to four cohorts to receive 20, 40 or 80 mg, of CALAS three times daily for seven days, or placebo. Each CALAS cohort included 15 subjects, and the placebo group included 10 subjects. A population PK model of CALAS was developed using plasma with four major alkaloid components. Metabolomics analysis was performed to identify biomarkers correlated with the therapeutic effect of CALAS, and efficacy and safety were assessed based on clinical symptoms and adverse events. RESULTS: The symptoms of acute bronchitis were alleviated by CALAS treatment without serious adverse events or clinically significant changes in vital signs, electrocardiography or upper abdominal Doppler ultrasonography. Moreover, one compartment model with first-order absorption showed that an increase in aspartate transaminase will reduce the clearance (CL) of scholaricine, and picrinine CL was inversely proportional to body mass index, while 19-epischolaricine and vallesamine CL increased with aging. The serum samples from acute bronchitis patients at different time points were analyzed using UPLC-QTOF in combination with the orthogonal projection to latent structures-discriminant analysis, which indicated higher levels of lysophosphatidylcholines, lysophosphatidylethanolamines and amino acids with CALAS treatment than with placebo. CONCLUSION: This is the first study to evaluate the clinical efficacy and explored the potential biomarkers related to CALAS therapeutic mechanism of acute bronchitis by means of clinical trial combined the metabolomics study. This exploratory study provides a basis for further research on clinical efficacy and optimal dosing regimens based on pharmacokinetics behavior. Additional acute bronchitis patients and CALAS PK samples collected in future studies may be used to improve model performance and maximize its clinical value.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Long-term follow-up of Chinese herbal medicines combined with conventional treatment in patients with acute coronary syndrome after percutaneous coronary intervention: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the prognosis effect of Chinese herbal medicines (CHMs) for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation (treatment group, 351 cases) or conventional treatment alone (control group, 351 cases) for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12th, 18th, 24th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization (PCI or coronary artery bypass grafting); and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events. RESULTS: A total of 621 (88.59%) patients completed 35.4±3.8 months follow-up, while 80 (11.41%) patients withdrew from the trial (41 in the treatment group and 39 in the control group). The incidence of primary endpoint was 5.7% (20 patients) in the treatment group versus 10.86% (38 patients) in the control group [relative risk (RR): 0.53; 95% confidence interval (CI): 0.30, 0.88; P=0.013; absolute risk reduction (ARR):-0.052, 95% CI: -0.06, 0.01]. The incidence of secondary endpoint was 5.98% (21 patients) in the treatment group versus 10.28% (36 patients) in control group (RR: 0.58, 95% CI: 0.33, 0.97, P=0.037; ARR: -0.043, 95% CI: 0.06, 0.01). Most of the primary and secondary endpoints were occurred in 18 months (84.50% in the treatment group versus 78.10% in the control group). CONCLUSION: CHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.

Effect of Xinyue capsules on patients with coronary heart disease after percutaneous coronary intervention: study protocol for a randomized controlled trial.

BACKGROUND: The risk of cardiovascular events remains high in patients with coronary heart disease (CHD) after successful percutaneous coronary intervention (PCI). Panax quinquefolius saponin, a major component of Xinyue capsule, has been used to treat patients with CHD. The aim of this study is to evaluate the efficacy and safety of Xinyue capsules in patients with CHD after PCI. METHODS/DESIGN: This study is a multicenter, placebo-controlled, double-blind, randomized controlled clinical trial. A total of 1100 participants are randomly allocated to two groups: the intervention group and a placebo group. The intervention group receives Xinyue capsules plus conventional treatment, and the placebo group receives placebo capsules plus conventional treatment. The patients receive either Xinyue or placebo capsules three times daily (1.8 g/day) for up to 24 weeks. The primary outcome measure is the time from randomization to the first occurrence of major adverse cardiovascular events. The secondary outcome measure is the time from randomization to the first occurrence of stroke, pulmonary embolism, and peripheral vascular events, as well as death due to any cause. All outcome measures will be assessed at 12, 24, 36, and 48 weeks after randomization. Adverse events will be monitored during the trial. DISCUSSION: The aim of this study is to evaluate the effects of Xinyue capsules on patients with CHD after interventional treatment. The results of this trial will provide critical evidence regarding Chinese herbal medicine treatment for CHD. TRIAL REGISTRATION: Chinese Clinical Trials Registry identifier ChiCTR-IPR-14005475. Registered on 10 November 2014.

Clinical efficacy of traditional chinese medicine on acute myocardial infarction: a prospective cohort study.

OBJECTIVE: To evaluate the clinical effects of Chinese medicine (CM) on acute myocardial infarction (AMI) with a prospective cohort study. METHODS: A total of 334 AMI patients from January 2007 to March 2009 were consecutively enrolled, and were assigned to a treatment group (169 cases) treated with combined therapy (CM for at least one month and Western medicine) and a control group (165 cases) with Western medicine alone. Clinical data including age, gender, smoking, medical history, infarction area, heart functional classification, CM syndrome scores, blood-stasis syndrome score, primary end-point (death, nonfatal myocardial infarction, and revascularization) and secondary end-point (ischemic stroke, rehospitalization due to angina, heart failure and shock), were collected. CM syndrome scores, blood-stasis syndrome score, primary end-point and secondary end-point were collected during the 6-month follow-up. Kaplan-Meier method was used for the survival analysis. The multifactor analysis was analyzed by Cox proportional hazards regression. RESULTS: At the end of 6-month the CM syndrome score and bloodstasis syndrome score in the treatment group were lower than those in the control group (P<0.01), especially the symptoms of chest pain, spontaneous perspiration and insomnia. Rehospitalization rate due to angina during the 6-month follow-up in the treatment group (2.96%) was lower than that in the control group (7.88%, P<0.05). Kaplan- Meier survival curve showed that event-free cumulated survival of rehospitalization due to angina during the 6-month follow-up in the treatment group was higher than that in the control group (Log rank 4.700, P=0.03). Cox regression analysis showed that heart dysfunction [hazard ratio (HR)=1.601, 95% CI=1.084-2.364, P=0.018] and diabetes mellitus (HR=1.755, 95% CI=1.031-2.989, P=0.038) were hazard factors to end-point, whereas CM (HR 0.405, 95% CI=0.231-0.712, P=0.002), percutaneous coronary intervention (PCI, HR=0.352, 95% CI=0.204-0.607, P<0.001) and angiotensin converting enzyme (ACE) inhibitors (HR=0.541, 95% CI=0.313-0.936, P=0.028) were protective factors. CONCLUSIONS: CM therapy could decrease CM syndrome scores and blood-stasis syndrome score, reduce the rehospitalization rate during 6-month follow-up due to angina. Heart dysfunction and diabetes mellitus were hazard factors to end-point, whereas CM, PCI and ACE inhibitors were protective factors.