Core outcome sets for myocardial infarction in clinical trials of traditional Chinese medicine and Western medicine.

BACKGROUND: Clinical trials of traditional Chinese medicine (TCM) and Western medicine showed there was heterogeneity of outcome reporting in myocardial infarction (MI). Developing a core outcome set (COS) might improve the consistency of outcome reporting in future clinical trials. METHODS: A list of outcomes was developed based on a systematic review of randomized controlled trials (RCTs) of MI and semistructured interviews with MI patients. Two rounds of Delphi survey for clinicians, researchers, journal editors, and methodologists were conducted. An online questionnaire sent to nurses. After an online consensus meeting, a COS for MI RCTs was developed. RESULTS: After extracted data from clinical trials and discussed, 216 outcomes were included in round 1 of the Delphi survey. Seventy-four participants completed round 1 of the Delphi survey. Sixty-five participants completed round 2 of the Delphi survey. Twenty-two nurses completed the online questionnaire. Fifteen participants attended the online consensus meeting, and 14 of them voted and determined the final COS. For all types of MI, it was recommended that left ventricular ejection fraction and quality of life be measured and reported. For acute MI, the participants in the consensus meeting recommended the following core outcomes: death from cardio-cerebrovascular disease, cardiogenic shock, heart failure, troponin I, troponin T, creatine kinase isoenzyme, Killip class, target vessel revascularization, and emergency CABG. For previous MI, recurrent MI, recurrent angina pectoris, and heart failure readmission were recommended. CONCLUSIONS: The COS for MI in RCTs provides recommendations for clinical trials that seek to improve outcomes for patients with MI.

Developing a core outcome set for assessing clinical safety outcomes of cardiovascular diseases in clinical trials of integrated traditional Chinese medicine and Western medicine: study protocol.

BACKGROUND: Integrative medicine is commonly used in China. Researchers prefer to report efficacy outcomes rather than safety outcomes in clinical trials; thus, evidence regarding safety in integrative medicine is unclear. Developing a core outcome set (COS) for safety outcomes is necessary. In this study, a representative example of the methodology for developing COS to assess safety outcomes of cardiovascular diseases in clinical trials investigating integrated medicine will be developed. METHODS AND ANALYSIS: Safety information will be extracted from package inserts and through systematic reviews of treatments for cardiovascular diseases (including angina pectoris, myocardial infarction, heart failure, arrhythmia, and hypertension) to develop an extensive list of safety outcomes, which will then be categorized according to whether subjective or objective outcomes. Questionnaires for clinician-reported safety outcomes and patient-reported safety outcomes will be developed. Two rounds of the Delphi survey will then be conducted for different stakeholders (traditional Chinese medicine clinicians and researchers in cardiovascular diseases, Western medicine clinicians and researchers in cardiovascular diseases, integrated medicine clinicians and researchers of cardiovascular diseases, pharmacologists, methodologists of evidence-based medicine, and patients). After round 2 of the Delphi analysis, a face-to-face consensus meeting will be held to determine the final COS for assessing safety outcomes in cardiovascular diseases. DISCUSSION: A COS for safety outcomes in cardiovascular diseases may improve the consistency of reporting results and will help identify potential bias of selective reporting in the future. TRIAL REGISTRATION: This study was registered in the Core Outcome Measures in Effectiveness Trials database as study 1564 .

Development of a Core Outcome Set for the Benefits and Adverse Events of Acute Heart Failure in Clinical Trials of Traditional Chinese Medicine and Western Medicine: A Study Protocol.

Aims: To identify a minimum set of efficacy and adverse events for patients with acute heart failure (AHF) among different stakeholders in clinical trials of traditional Chinese medicine and Western medicine. Methods and Analysis: First, we will develop a preliminary long list of outcomes that includes efficacy and adverse events/reactions via three steps: (i) systematic reviews of efficacy and safety outcomes for clinical trials of AHF; (ii) drugs included in the National Medical Insurance Catalog, the National Essential Medicines Catalog, and the WHO Essential Medicines List will be collected and safety outcomes extracted from the package inserts; and (iii) patients' or caregivers' semi-structured interviews will be carried out to add new viewpoints to the list. Second, after merging outcomes and grouping them under different outcome domains, questionnaires for health professionals and patients will be separately developed. Further, two rounds of Delphi survey for health professionals and a survey for patients and the public will be carried out. Third, different stakeholders will discuss and determine the final core outcome set (COS) for AHF in a consensus meeting. Ethics and Dissemination: The entire project has been approved by the Ethics Committee of the main institution. After the final COS is developed, it will be published and discussed widely in conferences. Clinical Trial Registration: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1566 (available at: https://www.cometinitiative.org/Studies/Details/1566).

[Meta-analysis of effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention].

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.

Evidence-based traditional Chinese medicine research: Two decades of development, its impact, and breakthrough.

It has been over 20 years since the introduction of evidence-based medicine (EBM) into the research of traditional Chinese medicine (TCM). The development of evidence-based TCM research has profoundly influenced the process of clinical research and decision-making, impelling researchers to pay attention to raise evidence quality, accumulate data, and explore appropriate evaluation methods adaptive to TCM original theories and knowledge. In this paper, the authors aim to summarize and review the existing work and seek promising research interests in this field, expecting to inspire more thoughts leading to breakthroughs in the near future.

Core Outcome Set for Clinical Trials of COVID-19 Based on Traditional Chinese and Western Medicine.

BACKGROUND: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. METHODS: A preliminary list of outcomes was developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses, and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Then different stakeholders participated in a consensus meeting by video conference to vote. RESULTS: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS included clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), and symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instruments/definitions were also recommended. CONCLUSION: Though there are some limitations for the research, such as insufficient patients and the public involvement, and the unbalanced stakeholders' region, the COS for COVID-19 may improve consistency of outcome reporting in clinical trials. It also should be updated with research progression.

The Application of Traditional Chinese Medicine Injection on Patients with Acute Coronary Syndrome during the Perioperative Period of Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: TCMI with the effect of Liqihuoxue and Yiqihuoxue has been applied as complementary therapies during the perioperative period of PCI for patients with ACS, while the recommended time points and plans of TCMI are still short of the support of evidence-based medicine. METHODS: A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of TCMI on patients with ACS during the perioperative period of PCI. RCTs were searched based on standardized searching rules in seven medical databases from the inception up to August 2019. Two reviewers conducted the study selection, data extraction, and quality analysis independently. Data were analysed with the support of software RevMan and Stata. RESULTS: A total of 68 articles with 6,043 patients were enrolled. The result of meta-analysis showed that the TCMI combined with western medicine was superior to the western medicine alone on clinical efficiency (before the PCI, before and after the PCI, or overall, P < 0.05), the occurrence of MACE (myocardial infarction and stenocardia: before the PCI, before and after the PCI, or overall, P < 0.05; arrhythmia: before and after the PCI, P < 0.05), and the level of inflammatory factors (hs-CRP: before the PCI, before and after the PCI, or overall, P < 0.05; IL-6: after the PCI, P < 0.05). The TCMI with the effect of Liqihuoxue obtained more support compared with Yiqihuoxue based on the result of meta-analysis. CONCLUSIONS: TCMI with the effect of Liqihuoxue or Yiqihuoxue combined with western medicine generally showed the potential advantage on the treatment of ACS during the perioperative period of PCI. However, the optimal time point of intervention and recommended plan based on the effect still needs more clinical evidence. We consider that the research of precise and standardized application of TCMI will be a promising direction for TCM in the future.

Rationale and design of the AUGUST-AHF Study.

AIMS: We aim to assess the effect of a lyophilized herbal injection on 90 day mortality and readmission rates in patients with acute heart failure (AHF). METHODS AND RESULTS: The AUGUST-AHF study is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 1270 hospitalized patients for AHF. Patients are randomized to receive YiqiFumai lyophilized injection (5.2 g/day) or placebo for 10 days, in addition to standard therapy, using a 1:1 ratio via an interactive web response system. The primary endpoint is the 90 day all-cause mortality or AHF readmission rates. Secondary endpoints include 180 day all-cause mortality or heart failure readmission rates, length of hospital stay for the indexed AHF, 90 day cardiac-specific mortality rate, occurrence of worsening heart failure through Day 10, changes in the Minnesota Living with Heart Failure Quality of Life scale score through Day 180, and 90 day major adverse cardiac events. Additional secondary endpoints include change in dyspnoea via visual analogue scale (VAS) and Likert 7-point comparator scale, N terminal pro-B-type natriuretic peptide value and New York Heart Association functional class, and the total amount of diuretics for the indexed AHF hospitalization. Study recruitment is expected to be completed by March 2021, and follow-up will end in September 2021. In an optional sub-study, patients will be followed up for 3 years. CONCLUSIONS: To our best knowledge, AUGUST-AHF is the first study assessing the efficacy of a Chinese herbal injection in patients with AHF. The results will be valuable to guide clinicians in using YiqiFumai lyophilized injection, which was included in the latest Chinese Health Insurance Catalog.

Risk factors associated with the severity of adverse drug reactions by Xiyanping injection: A propensity score-matched analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiyanping injection (XYP), extraction of Andrographis paniculate (Andrographis paniculata (Burm. f.) Nees, chuan xin lian), is a Chinese patent medicine approved to treat bronchitis in China. In 2017, safety incidents associated with treatment of XYP began to emerge throughout China. However, the risk factors of severity of adverse reactions by XYP remain uncertain. AIM OF THE STUDY: To determine risk factors for the severity of XYP-associated adverse drug reactions (ADRs). MATERIALS AND METHODS: We analyzed a total of 26,317 cases of ADRs linked to the use of XYP injection in the China National Adverse Drug Reaction Monitoring Information System from 2004 to 2017. Data were analyzed with respect to age, gender, ethnicity, previous ADRs, family history of ADRs, dosage specification, medication frequency specification, body weight, route of administration, herb-drug interactions (ribavirin, cefatriaxone, penicillin sodium, ambroxol hydrochloride, clindamycin, cefoxitin sodium, azithromycin, ceftazidime, amoxicillin sodium and clavulanate potassium, levofloxacin, cefazolin sodium pentahydrate, acyclovir) by univariate analysis and multivariate analysis. Propensity score matching was used to compare severity of (general or serious) ADRs. RESULTS: We included 24,911 cases of general ADRs and 1406 cases of serious ADRs. Univariate analysis identified age (p â€‹< â€‹0.001), body weight (p â€‹< â€‹0.001), route of administration (p â€‹= â€‹0.008), co-administration of XYP with ribavirin (p â€‹= â€‹0.031) as risk factors of severity of ADRs. Multivariate analysis identified XYP â€‹+ â€‹ribavirin combination (p â€‹= â€‹0.048) and age (p â€‹< â€‹0.001) as the independent risk factors. Upon propensity score matching, the variables were relatively balanced amongst the two groups of patients with general or severe ADRs, and the level of severity in patients who received treatment of XYP â€‹+ â€‹ribavirin increased (p â€‹= â€‹0.020). CONCLUSIONS: Age and co-administration of ribavirin may be potential risk factors for the severity of XYP-associated ADRs. This reminds us to pay more attention to the safety of elderly medication. Minimizing the herb-drug-interaction effects of XYP and ribavirin is a viable treatment target for healthcare professionals in managing serious ADRs amongst patients receiving XYP injection.

Development of a core outcome set for myocardial infarction in clinical trials of traditional Chinese medicine: a study protocol.

INTRODUCTION: Myocardial infarction (MI) is the most dangerous complication in patients with coronary heart disease. In China, there is an increasing number of randomised controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating MI. However, the inconsistency of outcome reporting means that a large number of clinical trials cannot be included in systematic reviews to provide the best evidence for clinical practice. The aim of this study is to develop a core outcome set (COS) for future TCM clinical trials of MI, which may improve the consistency of outcome reporting and facilitate the synthesis of data across studies in systematic reviews. METHODS AND ANALYSIS: We will conduct a systematic review of MI clinical trials with any intervention. Semistructured interviews will be conducted to obtain the perspectives of patients with MI. The outcomes from the systematic review and semistructured interviews will be grouped and used to develop a questionnaire. The questionnaire will be developed as a supplement for the TCM syndromes of MI and will be constructed from the results of a systematic review, existing medical records and a cross-sectional study. Then two rounds of the Delphi survey will be conducted with different stakeholders (TCM experts and Western medicine experts in cardiovascular disease, methodologists, magazine editors and patients) to determine the importance of the outcomes. Only the TCM experts will need to response to the questionnaire for core TCM syndromes. A face-to-face consensus meeting will be conducted to create a final COS and recommend measurement time for each outcome. ETHICS AND DISSEMINATION: This project has been approved by the Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine. The final COS will be published and freely available. TRIAL REGISTRATION NUMBER: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1243 (available at: http://www.comet-initiative.org/studies/details/1243).

Outcome reporting from clinical trials of non-valvular atrial fibrillation treated with traditional Chinese medicine or Western medicine: a systematic review.

OBJECTIVES: To examine variation in outcomes, outcome measurement instruments (OMIs) and measurement times in clinical trials of non-valvular atrial fibrillation (NVAF) and to identify outcomes for prioritisation in developing a core outcome set (COS) in this field. DESIGN: This study was a systematic review. DATA SOURCES: Clinical trials published between January 2015 and March 2019 were obtained from PubMed, the Cochrane Library, Web of Science, Wanfang Database, the China National Knowledge Infrastructure and SinoMed. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and observational studies were considered. Interventions included traditional Chinese medicine and Western medicine. The required treatment duration or follow-up time was ≥4 weeks. The required sample size was ≥30 and≥50 in each group in RCTs and observational studies, respectively. We excluded trials that aimed to investigate the outcome of complications of NVAF, to assess the mechanisms or pharmacokinetics, or for which full text could not be acquired. DATA EXTRACTION AND SYNTHESIS: The general information and outcomes, OMIs and measurement times were extracted. The methodological and outcome reporting quality were assessed. The results were analysed by descriptive analysis. RESULTS: A total of 218 articles were included from 25 255 articles. For clinical trials of antiarrhythmic therapy, 69 outcomes from 16 outcome domains were reported, and 28 (31.82%, 28/88) outcomes were reported only once; the most frequently reported outcome was ultrasonic cardiogram. Thirty-one outcomes (44.93%, 31/69) were provided definitions or OMIs; the outcome measurement times ranged from 1 to 20 with a median of 3. For clinical trials of anticoagulation therapy, 82 outcomes from 18 outcome domains were reported; 38 (29.23%, 38/130) outcomes were reported only once. The most frequently reported outcome was ischaemic stroke. Forty (48.78%, 40/82) outcomes were provided OMIs or definitions; and the outcome measurement times ranged from 1 to 27 with a median of 8. CONCLUSION: Outcome reporting in NVAF is inconsistent. Thus, developing a COS that can be used in clinical trials is necessary.