Yang Wang

Background: Despite the widespread use of inhalation therapy, patients with chronic obstructive pulmonary disease (COPD) frequently experience suboptimal disease control due to medication nonadherence, improper inhaler use technique, and inappropriate device selection, which collectively impair health-related quality of life (HRQoL). Pharmacist-led interventions may help address these gaps. Interventions based on the information-motivation-behavioral skills model and supported by digital tools can improve adherence and self-management. This study evaluates the efficacy of a multifaceted pharmaceutical care intervention for COPD delivered through digital tool support. Objective: The primary objective is to compare the change in HRQoL, measured using the St George’s Respiratory Questionnaire, between the intervention and control groups from baseline to 12 months. Secondary objectives are to assess changes in medication adherence (Test of Adherence to Inhalers), quality of life (EQ-5D-5L), COPD-related medical costs, and patient-reported pharmacy service experience. Methods: This 1-year cluster randomized controlled trial evaluates a multifaceted pharmaceutical care intervention in adults with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease, stages 2-4) who have confirmed suboptimal inhaler practice but remain matched to an appropriate inhaler device based on peak inspiratory flow rate measured using a digital tool. In total, 34 hospital-based cough and wheeze pharmaceutical care clinics were recruited and randomized (1:1) to either an intervention or a control group. The target sample size is 15 patients per site. Participants in the intervention group will receive tailored support using electronic adherence monitoring, inhaler use technique assessments, and peak inspiratory flow rate to optimize device selection and self-management. Participants in the control group will receive usual pharmaceutical care. Descriptive statistics will be used to summarize participant characteristics and outcomes. Linear mixed effects models will be used to compare primary and secondary outcomes. Subgroup analyses will explore effects by age, sex, education level, place of residence, and smoking status. Pharmacy service survey data will be analyzed qualitatively. Results: The trial was registered on July 15, 2024. Recruitment started on November 9, 2024, and enrollment was completed by December 31, 2025. As of December 31, 2025, we enrolled 454 participants, of whom 16 (3.5%) had completed the 12-month follow-up. The trial is expected to be completed by December 31, 2026, with results planned for publication in 2027. Conclusions: This multifaceted, pharmacist-led pharmaceutical care intervention may provide a scalable model for improving COPD management and HRQoL. If effective, the digitally supported program, grounded in the information-motivation-behavioral skills model, could be implemented in more than 1000 cough and wheeze pharmaceutical care clinics nationwide. Trial Registration: Chinese Clinical Trial Registry ChiCTR2400086943; https://tinyurl.com/75a9phbw International Registered Report Identifier (IRRID): DERR1-10.2196/82806

BACKGROUND Despite the widespread use of inhalation therapy, patients with chronic obstructive pulmonary disease (COPD) frequently experience suboptimal disease control due to medication nonadherence, improper inhaler use technique, and inappropriate device selection, which collectively impair health-related quality of life (HRQoL). Pharmacist-led interventions may help address these gaps. Interventions based on the information-motivation-behavioral skills model and supported by digital tools can improve adherence and self-management. This study evaluates the efficacy of a multifaceted pharmaceutical care intervention for COPD delivered through digital tool support. OBJECTIVE The primary objective is to compare the change in HRQoL, measured using the St George’s Respiratory Questionnaire, between the intervention and control groups from baseline to 12 months. Secondary objectives are to assess changes in medication adherence (Test of Adherence to Inhalers), quality of life (EQ-5D-5L), COPD-related medical costs, and patient-reported pharmacy service experience. METHODS This 1-year cluster randomized controlled trial evaluates a multifaceted pharmaceutical care intervention in adults with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease, stages 2-4) who have confirmed suboptimal inhaler practice but remain matched to an appropriate inhaler device based on peak inspiratory flow rate measured using a digital tool. In total, 34 hospital-based cough and wheeze pharmaceutical care clinics were recruited and randomized (1:1) to either an intervention or a control group. The target sample size is 15 patients per site. Participants in the intervention group will receive tailored support using electronic adherence monitoring, inhaler use technique assessments, and peak inspiratory flow rate to optimize device selection and self-management. Participants in the control group will receive usual pharmaceutical care. Descriptive statistics will be used to summarize participant characteristics and outcomes. Linear mixed effects models will be used to compare primary and secondary outcomes. Subgroup analyses will explore effects by age, sex, education level, place of residence, and smoking status. Pharmacy service survey data will be analyzed qualitatively. RESULTS The trial was registered on July 15, 2024. Recruitment started on November 9, 2024, and enrollment was completed by December 31, 2025. As of December 31, 2025, we enrolled 454 participants, of whom 16 (3.5%) had completed the 12-month follow-up. The trial is expected to be completed by December 31, 2026, with results planned for publication in 2027. CONCLUSIONS This multifaceted, pharmacist-led pharmaceutical care intervention may provide a scalable model for improving COPD management and HRQoL. If effective, the digitally supported program, grounded in the information-motivation-behavioral skills model, could be implemented in more than 1000 cough and wheeze pharmaceutical care clinics nationwide. CLINICALTRIAL Chinese Clinical Trial Registry ChiCTR2400086943; https://tinyurl.com/75a9phbw INTERNATIONAL REGISTERED REPORT DERR1-10.2196/82806

Introduction: While transcatheter aortic valve replacement (TAVR) has become a well-established standard of care for patients with symptomatic severe aortic stenosis, the optimal antithrombotic strategy post-TAVR remains a subject of debate, particularly in patients without clear indications for anticoagulation or dual antiplatelet therapy. This study aims to investigate the safety and efficacy of rivaroxaban compared with antiplatelet monotherapy in this specific patient population. Methods and analysis: This study is designed as a prospective, multicentre, open-label, randomised controlled trial. A total of 454 patients, who have successfully undergone TAVR and do not have indications for long-term anticoagulation or dual antiplatelet therapy, will be consecutively enrolled from seven centres across China. Participants will be randomly assigned to receive either anticoagulation with rivaroxaban (20/15 mg) or conventional antiplatelet therapy (aspirin or clopidogrel) for 1 month. Follow-up evaluations are scheduled at 1, 3, 6 and 12 months post-procedure. After the initial 1-month antithrombotic therapy, the regimen may be adjusted by the investigator based on the patient’s clinical and imaging follow-up results. The primary endpoint is a hierarchical composite of cardiovascular death, first occurrence of myocardial infarction or stroke, first occurrence of life-threatening, disabling or major bleeding, and grade 3 or higher hypo-attenuated leaflet thickening and reduced leaflet motion at 12 months post-TAVR. The win ratio method will be employed to analyse the primary endpoint. Ethics and dissemination: This trial was approved by the Ethics Committee of the Beijing AnZhen Hospital. All relevant results will be disseminated through publications in peer-reviewed journals and presentations at conferences. Trial registration number: ChiCTR2400087453.

Background: To assess the consequence of different degrees of missing primary endpoint data for randomized controlled trials and to find the influence factors. Methods: PubMed, Cochrane Library, EMBASE and ClinicalTrials.gov were searched up to Nov 30, 2023. We included trials of the drug-coated balloon/drug-eluted stent with angiographic outcomes as the primary endpoint. The tipping-point analysis was used to deal with the missing data for the primary endpoint. The inconsistency rate, tipping-point standardized effect size (SES) and tipping-point ratio were used to assess the result robustness. Results: A total of 101 trials were included, which had 109 trial comparisons. Among them, 89 (81.7%) comparisons had superior/non-inferior conclusions (H₀ rejected); 85 (78.0%) comparisons had a missing rate of ≥ 10%, and 30 (27.5%) comparisons had a missing rate of ≥ 20%. For H₀ rejected comparisons with a missing rate of ≥ 10%, the median of inconsistency rate, tipping-point SES and tipping-point ratio was 32.2% (IQR 19.7%, 45.4%), 0.90 (IQR 0.17, 1.79) and − 1.53 (IQR − 2.43, − 0.39). A higher missing rate and a larger (worse) observed-target SES were associated with a more unreliable result. Conclusion: A high dropout rate and inflated target effect size could cause an unreliable result. We emphasize a robust evaluation of the results for clinical trials with missing data for the primary endpoint. Plain Language Summary: Missing data for the primary outcome has a great impact on the interpretation of clinical trials. This study included 101 randomized controlled trials of the drug-coated balloon or drug-eluted stent with an angiographic primary endpoint and used three indicators to assess the result robustness. This study found that 78.0% trial comparisons had a missing rate of ≥ 10%, and 27.5% comparisons had a missing rate of ≥ 20%; The conclusions of some clinical trials may change after dealing with the missing data; A higher missing rate and an inflated target effect size were associated with a more unreliable result.

Introduction: The prevalence of atrial fibrillation (AF) is increasing globally, and stroke prevention is the key to reduce the morbidity and mortality related to AF. Currently, direct oral anticoagulants (DOACs) are the primary options for stroke prevention, while it increases risk of bleeding. Left atrial appendage (LAA) is suspected as a vital source of cerebral emboli and may lead to ischaemic stroke, and thoracoscopic LAA clipping procedure provides an alternative option for stroke prevention in high-risk patients. However, high-quality evidence comparing LAA clipping to DOACs in terms of stroke prevention is lacking. This trial is designed to assess whether the efficacy of thoracoscopic LAA clipping is superior to DOACs for stroke prevention in AF patients at high risk of thrombosis (CHA₂DS₂-VASc≥2 in men and ≥3 in women)[CHA2DS2-VASc stands for "congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female)”].Methods and analysis: This is a prospective, multicentre, open-labelled, randomised controlled study. This trial will randomly assign 290 patients with non-paroxysmal AF to thoracoscopic LAA clipping group or DOAC therapy group in a 1:1 randomisation. The primary endpoint is defined as a composite endpoint event consisting of stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events at 24 months after randomisation. The secondary endpoints consist of the components of the primary composite endpoint, surgery-related adverse events and minor bleeding events.Ethics and dissemination: The central ethics committee at Fuwai Hospital approved the trial entitled “Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation (LAA-CLIP trial)”. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration number: NCT06021808.

Introduction The strategy for initiating antithrombotic therapy to prevent bioprosthetic valve thrombosis (BPVT) after transcatheter aortic valve replacement (TAVR) remains uncertain. There is still lacking evidence on the efficacy and safety of early 6 months usage of single-antiplatelet therapy (SAPT) or oral anticoagulant (OAC) after TAVR in patients without anticoagulant indications. Methods and analysis This is a multicentre, randomised controlled, open-label trial, and 650 patients undergoing TAVR from 13 top TAVR centres in China will be recruited. Each eligible participant will be randomly assigned to two groups (1:1 ratio) as (1) SAPT (aspirin 75–100 mg for 6 months) group or (2) OAC group (warfarin, therapeutic international normalised ratio at 1.8–2.5 for 6 months), both followed by sequential aspirin 75–100 mg for 6 months. Participants in both groups will be invited for three follow-up visits of 1, 6 and 12 months after discharge. We will use both the net clinical benefit endpoint (composite of all-cause mortality, myocardial infarction, stroke/transient ischaemic attacks, peripheral artery thrombosis, intracardiac thrombosis and major bleeding and disabling or life-threatening bleeding) and the BPVT endpoint evaluated by four-dimensional CT as our primary endpoints. P value of Ethics and dissemination The present study was approved by the Institutional Review Boards at Fuwai Hospital, National Center for Cardiovascular Diseases of China (Approval No. 2023-1947). All patients will be informed of the details of the study and will sign an informed consent prior to inclusion in the study. Results of this study will be published in a peer-reviewed journal. Trial registration number NCT05375474.

Introduction: Dual antiplatelet therapy (DAPT), referred to as the combination of aspirin and P2Y ₁₂ receptor antagonist (clopidogrel or ticagrelor), potentially improves patency of saphenous vein grafts (SVG) after coronary artery bypass grafting (CABG), while it is further proposed that DAPT potentially increases bleeding risk. Compared with DAPT, de-escalated DAPT (De-DAPT) is an effective antiplatelet strategy for acute coronary syndrome treatment, which significantly reduces the risk of bleeding without increasing the incidence of major adverse cardiovascular events. However, insufficient evidence is available to determine the timing of DAPT after CABG. Methods and analysis: The Timing of Platelet Inhibition after Coronary Artery Bypass Grafting (TOP-CABG) is a multicentre, randomized, double-blind, parallel controlled trial, which is conducted in sixteen centres in China. TOP-CABG aims to compare one-year patency rate of SVG between De-DAPT and DAPT and to explore the impact of the two regimens on bleeding events. A total of 2, 300 patients undergoing isolated CABG will be randomized 1:1 to De-DAPT referred to as ticagrelor+aspirin during first three months post-CABG and aspirin+ticagrelor placebo for next nine months or to DAPT group with ticagrelor+aspirin for one year after CABG. Patients, treating physicians and investigators will be blinded to allocation. Patients are evaluated at one, three, six, nine and twelve months post-operatively through an outpatient hospital visit. At one year after CABG, patients are required to take coronary CT angiography (CCTA). The primary efficacy endpoint is occlusion of SVGs and the primary safety endpoint is risk of bleeding episodes (the Bleeding Academic Research Consortium (BARC) classification ≥2) within 1-year after CABG. Secondary outcomes include SVG failure, significant (≥70%) venous or arterial graft stenosis and a series of major adverse cardiovascular events within one year after CABG. Ethics and dissemination: The Ethics Committee in Fuwai hospital approved this study (2022-1774). Fifteen centres agreed to participate the TOP-CABG trial, and the study has been approved in these 15 centres by whose ethics committee. The results of the trial will be submitted for publication in a peer-reviewed journal. Trial registration number: NCT05380063 .