Contemporary Clinical Trials Communications

BackgroundNearly half of the world population is infected by Helicobacter pylori (H. pylori). Bismuth-containing quadruple therapy (BQT) has shown favorable outcomes. This study compares 10-day and 14-day BQT regimens to evaluate their efficacy, safety, and compliance rates. MethodsWe searched electronic databases from their inception until May 2024 to retrieve all randomized controlled trials (RCTs) that compared 10-day and 14-day BQT regimens for H. pylori eradication. Meta-analysis was performed using Review Manager 5.4. Dichotomous outcomes were compared using risk ratio (RR). ResultsSeven RCTs and a total of 2,424 patients were included in the meta-analysis. There was no significant difference in the intention-to-treat eradication rate (RR 0.97; 95% CI 0.94, 1.01) and the per-protocol eradication rate (RR 0.96; 95% CI 0.93, 1.00) between the 10-day BQT and 14-day BQT groups. Commonly reported adverse events in both groups were epigastric pain and discomfort, nausea, and vomiting. There was no significant difference in the risk of adverse events between the two groups (RR 0.80; 95% CI 0.63, 1.02). There was no significant difference in the compliance rate between the two groups (RR 1.02; 95% CI 1.00, 1.04). ConclusionThe eradication rates, risk of adverse events, and compliance rates were comparable between the two groups. Future research comparing similar drug doses with larger sample sizes and longer patient follow-ups can improve the quality of results. HighlightsO_LIOur meta-analysis comprising 2424 patients showed that patients receiving 10-day bismuth-containing quadruple therapy had comparable eradication rates to those receiving 14-day bismuth-containing quadruple therapy for Helicobacter pylori. C_LIO_LIAdditionally, there was no significant difference between the two groups for compliance and risk of adverse events. C_LIO_LIAntibiotic resistance was associated with lower eradication rates in both treatment groups. C_LI

BackgroundIrregular bowel habits including constipation are common gastrointestinal issues, significantly impacting quality of life. While conventional pharmacological treatments exist, they often come with side effects and offer limited long-term relief, driving interest towards safer, effective herbal alternatives. Cassia fistula (C. fistula) has long been recognized for its laxative properties and has been reported to be a safer alternative to Senna (Cassia angustifolia). PurposeThis study aimed to evaluate the efficacy and safety of a standardized extract of C. fistula compared to Senna extract in healthy individuals experiencing irregular bowel habits. MethodsA two-arm, open-label, randomized, multicentric, interventional, prospective clinical study was conducted in India with 70 participants (35 per group). One group received the standardized C. fistula extract and the other group received Senna extract for 14 days, followed by a 7-day post-consumption follow-up. Primary outcomes included changes in bowel movement frequency. Secondary outcomes assessed stool consistency (Bristol Stool Form Scale), straining, bowel satisfaction after defecation, anorectal blockage, use of manual manoeuvres, average time spent on defecation, time to first bowel evacuation post intervention and associated clinical symptoms (headache, belching, flatulence, abdominal distension, acidity). Safety was evaluated through vitals, laboratory parameters, and adverse events. ResultsC. fistula extract significantly increased bowel movement frequency (3.30 {+/-} 0.92 to 5.90 {+/-} 1.24 at Day 14, p<0.05) and improved stool consistency comparable to Senna extract. Straining and bowel satisfaction after defecation also significantly improved with the use of C. Fistula. Notably, C. fistula extract showed significantly greater reduction in the sensation of anorectal blockage at Days 14 and 21 (p<0.05) and a faster onset of action (shorter time to first defecation) compared to Senna. Associated symptoms of constipation also reduced significantly. C. fistula extract was better well-tolerated, with fewer product-related adverse events compared to Senna. ConclusionC. fistula extract was found to be effective in irregular bowel habits, offering comparable efficacy to Senna while proving to be superior in reducing the sensation of anorectal blockage and achieving a faster time to first bowel evacuation. It also demonstrated a more favorable safety profile with significantly fewer product-related adverse events. Therefore, C. fistula extract represents a promising non-habit-forming herbal alternative for bowel regulation.

BackgroundClinical trial recruitment is often the rate-limiting step in the development of new treatments reaching patients across all disease states. With more than 1500 currently available clinical trials for inflammatory bowel diseases (IBD) patients, it is important to understand patient perceptions of clinical trial participation to improve recruitment and retention. This study aimed to examine the specific challenges and barriers that might be reducing IBD patient enrollment and potential methods to overcome these barriers. MethodsFive in-person patient focus groups were conducted from February through May 2016 using two facilitation guides. Participants self-reported a diagnosis of Crohns disease or ulcerative colitis. ResultsThe five focus groups included a total of 34 participants. Participants discussed several barriers, including fears, disease severity at trial onset, potential adverse effects, time constraints, and the influence of both their primary IBD provider and support network. Methods to improve participation included better communication to prospective patients, reduced length of trial and time commitment, lower placebo rates, the option of open label extension, and support of the patients primary IBD provider. ConclusionsThis is the first study to examine patient perceptions for IBD clinical trial enrollment, including barriers to participation and methods to improve participation. Fear and misunderstanding of clinical trials, engagement with providers, limiting time demands, and limiting the impact on work and family were found to be barriers to participation. Creative solutions to these problems could lead to greater participation in trials and more rapid advancement of new therapies to clinical approval and use.

ObjectivesTo investigate how nutrition readiness to change influences implementation of dietary behavior changes and to compare the gut microbiomes and document gut microbiome composition changes over time in individuals with early Alzheimers disease dementia (eAD), mild cognitive impairment (MCI), and healthy controls (HC) Overall, this study aims to add to the emerging field of how the gut microbiome influences the nervous system. MethodsThis is a sub-study of a multi-prong proof-of-concept, observational study mapping the gut microbiome: 15 HC, 15 MCI, 15 eAD (n=45). At 0-, 3-, and 6-months, participants are provided lifestyle recommendations tailored to their gut microbiome. Participants may choose to implement this or not and are observed throughout (observational intervention study). In this sub-study, a survey is developed and implemented in conjunction with dietary assessment (DietID) to evaluate the role of Readiness to Change in implementation of dietary recommendations. ResultsThis is the sub-study protocol from an ongoing parent study. DiscussionThis protocol presents a novel intervention to assess the gut microbiome, individual dietary patterns, and readiness to make lifestyle change related to diet. Trial RegistrationNCT06039267

Background: Large language models (LLMs) offer promise for systematic review data extraction, but performance in complex multidisciplinary domains and utility for clinical statement generation remain insufficiently described. Objectives: To evaluate Google NotebookLM for AI-assisted data extraction and RAND/UCLA consensus statement generation in a systematic review of IBD, obesity, and cardiometabolic comorbidities. Methods: Studies were organized into domain-specific notebooks; structured prompts generated standardized evidence tables. Two independent reviewers validated outputs against full-text articles using a four-category error classification. Cell-level accuracy and critical accuracy (cells free of major factual errors) were the primary metrics; workflow time was compared against a published conventional extraction benchmark. Concordance between AI-generated and expert-finalized statements was assessed. Results: Across 57 articles, 1,710 data cells were extracted; 151 (8.83%) were flagged, yielding 91.17% cell-level accuracy. Major factual errors occurred in only 4 cells (0.23%), for a critical accuracy of 99.77%. Most errors were minor omissions (59.6%) or incomplete extractions (30.5%); domain error rates ranged from 7.08% to 11.33%. The pipeline required 17.7 versus a projected 165.1 person-hours (89.3% reduction). PICO-structured prompting generated 70 candidate statements; 58 of 112 finalized panel statements (51.8%) were AI-derived, and 85.7% were retained in the finalized set. Conclusion: Google NotebookLM demonstrates feasibility as a primary extraction and synthesis tool in a multidisciplinary systematic review, with extractive incompleteness as the principal limitation and substantial time savings over conventional approaches. Its novel application to RAND/UCLA consensus statement generation extends AI-assisted evidence synthesis to clinical consensus generation workflow.

IntroductionChronic atrophic gastritis (CAG) is a precancerous disease that is difficult to treat. Even after eradication of the Helicobacter pylori (HP) infection, complete resolution of the symptoms is difficult to achieve. The fortifying the spleen, clearing heat, activating blood method (FSCHABM) has an excellent curative effect in the treatment of CAG. A real-world study is particularly suitable for researching the treatment of CAG, but there are currently no reports on CAG trials. Our aim is to design a high-quality trial to investigate the efficacy and safety of FSCHABM in treating CAG patients. Methods and analysisThis protocol is designed as a real-world study for 10 years. A total of 5000 participants will be assigned to a FSCHABM treatment group or a non-FSCHABM treatment group at a 1:1 ratio at the first Affiliated Hospital of Guangzhou University of Chinese Medicine. Patients are given 1-2 courses of a 24-week-long treatment. The participants will be followed up for observation and measurement of the following indicators: the primary outcome is the histopathological indicator; the secondary outcome includes evaluation of gastric lesions, syndrome curative effect, evaluation of symptoms, evaluation of quality of life, evaluation of anxiety and depression, economic evaluation and other indicators. This is the first real-world study evaluating the therapeutic effect of FSCHABM in the treatment of CAG in clinical practice. This protocol can provide a reference for future multi-center, randomized, controlled trials. Strengths and limitations of this studyit is the first time to carry out TCM study related to CAG by using the real-world study. A large number of patients and a long-term study can effectively reflect the effect of TCM treatment and reduce the bias. The precise research protocol makes the whole research more accurate and reliable. The limitations of implementing this protocol are expending a lot of time, manpower and economic resources inevitably. Ethics and disseminationthis study was approved by Ethical committee of the first Affiliated Hospital of Guangzhou University of Chinese Medicine. Study findings will be shared with participants, healthcare providers, and policymakers through research reports, conference presentations, and the Internet. The results will also be disseminated through publication in peer reviewed journals. Trial registrationThe registration number, ChiCTR1900027177, was assigned by the Chinese Clinical Trial Registry on 3 November 2019. FundingThis work was supported by Guangdong natural science fund project, China (2019),No.2019A1515011145; Major research project of Guangzhou University of Chinese medicine, China (2019), No.A1-2606-19-110-007; The first affiliated hospital of Guangzhou University of Chinese medicine "innovation foster hospital" clinical research project, China (2019), No.2019IIT19; Guangdong natural science foundation (PhD) project, China (2017), No.2017A030310121; The first affiliated hospital of Guangzhou University of Chinese medicine "innovation foster hospital" innovation research team project, China (2017), No.2017TD05; The first affiliated hospital of Guangzhou University of Chinese medicine "innovation foster hospital" Youth scientific research talent training program, China (2015), No.2015QN09.

BackgroundDiarrheal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. This article describes a protocol for a cluster randomized trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition. MethodsWe will conduct a mixed-methods, parallel cluster randomised controlled trial with baseline measures. 120 clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. Participants will be mother-child dyads (27 per cluster period) with children aged 6 to 24 months. Data collection will comprise a day of observation and interviews with each participating mother-child pair and will take place at baseline and four and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutritional content of meals, and child anthropometry. A secondary structural equation analysis will be conducted to examine the causal relationships between the different outcomes. ConclusionsThe trial will provide evidence on the effectiveness of community-based behavioural change and educational interventions designed to reduce the burden of diarrhoeal disease in the under fives, and how effectiveness varies across different contexts.

ObjectivesPatient recruitment is a critical factor for successful completion of a clinical trial. Decentralized trial recruitment allows potential subjects to be identified via the electronic health record (EHR) and approached through digital channels. We sought to understand the real-world effectiveness of decentralized trial recruitment leveraging electronic patient reported outcomes (ePROs) in patients with inflammatory bowel disease (IBD). MethodsAs part of a National Institutes of Health (NIH) funded multi-site clinical trial, we designed an EHR-integrated decentralized trial recruitment process to contact eligible patients at three tertiary IBD centers. We leveraged the Commure Engage/Rx.health (Mountain View, California) digital health formulary and automation engine integrated with Epic Systems (Epic Systems, Verona, WI) to digitally approach patients in an automated manner (with human-in-the loop) to complete the online enrollment process and monitor adherence with ePROs. ResultsUsing digital outreach complemented by in-person engagement, we approached 6,687 eligible patients over 12 months and successfully enrolled 543 patients (mean age 40.7 {+/-} 15.7 years, 63.3% females, 39.4% ulcerative colitis, 60.6% Crohns disease). 81.2% were recruited from bulk outreach methods. Gender (P<0.01), and race (P<0.01) were significantly associated with digital clinical trial enrollment. Patients were continually monitored with ePROs throughout the duration of the study. ConclusionsThis is one of the first studies to show the feasibility and successful recruitment of patients with IBD using automated digital outreach. We found a combination of outreach methods with human in the loop an effective strategy for clinical trial accrual. These findings suggest that ePROs can be successfully used in IBD centers to support treat-to-target strategy. Study HighlightsO_LIWhat is Known: O_LIThe most common reason for clinical trial failure is lack of accrual. C_LIO_LIClinical trial recruitment strategies have remained largely unchanged despite technological advances. C_LIO_LIThere is limited real world data around the use of electronic patient reported outcomes on a digital platform for patients with inflammatory bowel disease C_LI C_LIO_LIWhat is New Here O_LIne of the first studies to employ a prospective decentralized recruitment approach for a multicenter clinical trial in inflammatory bowel disease. C_LIO_LIfeasibility of an automated digital outreach for enrollment and continued monitoring using electronic patient reported outcomes C_LI C_LI

ObjectiveTo evaluate the effect of oral vitamin D supplementation on colorectal cancer incidence and mortality. MethodsAll randomized controlled trials regarding effect of oral vitamin D on colorectal cancer from PubMed, Web of science, Embase and Cochrane Library were searched. Meta analysis and trial sequential analysis of included studies were carried out. ResultsSeven RCTs enrolling 72810 participants were included. Compared with placebo, oral vitamin D supplementation was not associated with the incidence of colorectal cancer(RR=1.1,95%CI:0.93-1.31;p=0.28).Subgroup analysis showed no difference in female participants for incidence of colorectal cancer(RR=1.04,95% CI:0.84-1.28;p=0.73). The pooled RR, included 41643 participants, showed no difference in mortality of colorectal cancer(RR= 0.82, 95% CI:0.56 to 1.21; p = 0.32). Trial sequential analysis showed the z-line did not cross the conventional test boundary, TSA monitoring boundary and futility boundaries. ConclusionOral vitamin D supplementation offers no benefit on the incidence and mortality of colorectal cancer. However, the RCTs with longer follow-up are needed to ascertain the efficacy of Vitamin D, especially among adults with lower serum 25(OH)D levels in future.

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) have risen substantially in prevalence over recent decades, driven by a growing global burden of obesity, diabetes mellitus, and other cardiometabolic risk factors. In response, researchers have intensified efforts to evaluate novel and re-purposed therapies that may prevent or reverse disease progression. Although several pharmacological therapies are under investigation, robust comparative evidence on their relative effectiveness and safety remains limited. We will therefore conduct a systematic review and network meta-analysis (SRNMA) of randomized controlled trials (RCTs) evaluating pharmacological therapies for adults with MASLD or MASH. MethodsWe will search four electronic databases (Ovid MEDLINE, Embase, CINAHL and Cochrane CENTRAL) from inception to August 2025 without language and other restrictions. Eligible studies will include parallel-arm RCTs enrolling [&ge;]10 adults per arm with MASLD or MASH; comparing any pharmacological therapy to standard care, no treatment, lifestyle modifications, placebo or alternative pharmacotherapies; and having a minimum follow-up duration of 12 weeks. Primary clinical outcomes are all-cause mortality, cardiovascular mortality, hospitalization, progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, and serious treatment-related adverse events. Surrogate outcomes include histological, imaging, biochemical, and metabolic markers of disease activity. Paired reviewers will independently screen identified hits for eligibility, extract data from eligible studies, and assess risk of bias using the Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials (ROBUST-RCT). We will conduct separate NMAs for MASLD and MASH populations using a frequentist graph-theoretic random-effects model. Certainty of evidence will be assessed using GRADE. Subgroup and sensitivity analyses will explore effect modification by comorbidities and study quality. Ethics and DisseminationNo ethics approval is required. Results will be disseminated via peer-reviewed publication and conference presentations to inform clinicians, guideline developers, and health system decision-makers. PROSPERO Registration NumberCRD420251103235.

IntroductionSarcopenia is the age-related loss of muscle mass and strength. It is associated with significant adverse personal and health-economic outcomes. Despite advances in understanding the biology of muscle ageing, effective treatments remain limited. Exercise is currently the only proven intervention, but many older people are unable or unwilling to sustain the intensity of exercise required to gain results. Consequently, there is a major unmet need for new therapies. REVITALiSE is an early-phase experimental medicine platform trial designed to efficiently evaluate promising interventions in people with sarcopenia. By identifying and selecting the most promising interventions to progress to large randomised controlled trials, REVITALiSE aims to accelerate the development of effective therapies for this under-served population. Methods and analysisThe REVITALiSE platform comprises a series of parallel-group, individually randomised, controlled, open-label, proof-of-concept subtrials. Each subtrial will enrol 30 participants aged 65 years and older with probable sarcopenia, defined according to the European Working Group on Sarcopenia in Older People (EWGSOP) guidelines. The platform is designed to evaluate a range of interventions, including exercise-based approaches, device-based therapies, and nutraceuticals. Participants will be randomised in a 1:1 ratio to receive either the intervention or usual care. The primary outcome, analysed in a modified intention to treat (mITT) population, is the between-group difference in four-metre walking speed between baseline and 12-week follow-up. Secondary outcome measures specified in the master protocol include handgrip strength, the Short Physical Performance Battery (SPPB), and lean muscle mass (assessed by Dual X-ray absorptiometry). Muscle biopsies of the vastus lateralis will also be taken at baseline and follow-up. Additional mechanistic outcomes will be determined by the proposed mode of action of each intervention and specified in the relevant subtrial annex. Adverse events will be recorded for the duration of the trial. Ethics and disseminationUK Health Research Authority and Northeast - Tyne and Wear South Research Ethics Committee (IRAS 352708). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community. Trial registration number: ISRCTN10801475 Protocol V1.0 08 May 2025 Sponsor: Newcastle Upon Tyne NHS Foundation Trust REC: NE Tyne and Wear South NHS Research Ethics Committee ref: (IRAS 352708; ref: 25/NE/0115)

BackgroundVascular dementia (VaD) accounts for 15-20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng, Ginkgo biloba and Crocus sativus extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention. MethodsA rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimers disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimers Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinicians Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies. DiscussionPrimary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD. Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN 12616000057482. Registered on 20 January 2016. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369471&isReview=true

IntroductionPeptic ulcer (PU) is prone to recurrence and can have a prolonged course, significantly impacting patients quality of life. Clinical treatment commonly involves combating Helicobacter pylori(HP), reducing gastric acid secretion, and promoting gastric mucosal protection. Nevertheless, Western medicine often entails various adverse effects and long-term use. Consequently, numerous scholars have redirected their focus towards traditional Chinese medicine (TCM) for external treatments of PU due to its minimal toxicity, fewer side effects, and lower recurrence rates. This study aims to assess the efficacy and safety of Acupoint herbal patching (AHP) in treating PU, offering a foundation for future clinical investigations. Methods and analysisThe computer will conduct a comprehensive search for relevant studies on the utilization of AHP in the management of PU from the inception of the database in various scholarly platforms including China Journal Network, Wanfang Database, Chongqing Wipo Database, China Biomedical Literature Database, PubMed, and Cochrane Library. Eligible literature will undergo meticulous scrutiny based on predefined criteria, with data extraction and quality assessment executed independently by two researchers. Meta-analysis utilizing RevMan 5.4.1 software will be employed to synthesize the collected data. The study will focus on the TCM Symptom Score Scale as the primary outcome measure, while secondary outcomes will encompass serum inflammatory factors, endoscopic findings, quality of life, recurrence rate, and adverse events. Furthermore, assessments on effectiveness, cure rate, and potential publication bias will be carried out. This investigation aims to assess the efficacy of AHP in the treatment of PU and its impact on enhancing the well-being of patients. Ethics and disseminationSince the present work constitutes a literature review, it is important to note that ethical approval is deemed unnecessary. The outcomes of this investigation are intended for dissemination in a scholarly periodical subject to peer review. PROSPERO registration numberCRD42023456995 STRENGTHS AND LIMITATIONS OF THIS STUDYA thorough examination of the literature will be undertaken across six electronic databases in both Chinese and English languages. The methodology will adhere to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Evaluation of the studies quality will be conducted utilizing the updated Cochrane Risk of Bias 2.0 tool. Variations in patch locations and treatment protocols may introduce significant heterogeneity, posing challenges to the synthesis of data.

Background: The Cilostazol Albumin Treatment in Subarachnoid Hemorrhage (CATS) trial evaluates eight active cilostazol-human albumin regimens plus control in patients with aneurysmal subarachnoid hemorrhage. We summarized the rationale for the primary statistical design, compared alternative Phase II methodologies, and evaluated reduced-arm sensitivity scenarios. Methods: The binary primary endpoint is Common Data Elements-defined delayed cerebral ischemia within 14 days after randomization. The selected design is Bayesian adaptive, with a burn-in phase, response-adaptive randomization among active arms while maintaining fixed control allocation, four interim analyses, early stopping for expected success or futility, and a two-dimensional normal dynamic linear model. Primary operating characteristics were obtained from 1,000 virtual trials per scenario using Fixed and Adaptive Clinical Trial Simulator version 7.0.0. Exploratory simulations evaluated six-, four-, and two-active-arm configurations and simplified alternative designs. Results: Compared with fixed equal allocation, the Bayesian adaptive design preserved an approximately 10% false-success probability under the global null while improving probability of success and efficiency in clinically relevant scenarios. Under the Realistic scenario, probability of success increased from 0.61 to 0.86, expected sample size decreased from 400 to 308, and expected duration decreased from 235 to 187 weeks. Under common thresholds, null probability of success was 0.098 for the full anchor and 0.073 for Reduced-6; Reduced-6 probabilities of success were 0.774 and 0.765 in the Realistic and Realistic2 scenarios. However, Reduced-6 omitted two monotherapy anchors and was less robust in Backwards2. In the comparator simulation, the selected design had probability of success of 0.858 and expected sample size of 308.3 under the Realistic scenario, compared with 0.624 to 0.845 and approximately 352 to 400 for simplified comparators. Conclusions: For identifying the most promising cilostazol-human albumin regimen for Phase III rather than confirming efficacy, the Bayesian response-adaptive design with two-dimensional normal dynamic linear model borrowing is more efficient and better aligned than simplified comparators. The full nine-arm design remains preferable because it preserves the complete therapeutic discovery space and is more robust to misspecified or non-smooth response surfaces.

IntroductionSustained virological response (SVR) is commonly used as an indicator of treatment success in people with chronic hepatitis C virus (HCV) infection. However, there is uncertainty on whether SVR is a validated surrogate marker of successful treatment of chronic HCV infection. AimTo evaluate whether SVR is a good surrogate for all-cause mortality, decompensated cirrhosis, or any specific aspect of liver decompensation (jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, or variceal haemorrhage), or hepatocellular carcinoma in people with chronic HCV infection eligible to receive direct-acting antiviral drugs. MethodsO_ST_ABSData sourceC_ST_ABSTwo ongoing systematic reviews on the effectiveness of direct-acting antiviral drugs in chronic HCV infection. AnalysisO_LIEstimate the regression coefficients or between-studies correlation between SVR and the event by three different Bayesian approaches with OpenBUGS, as outlined in the guidance by the Evidence Synthesis Unit (Technical support document 20). C_LIO_LIEstimate the average proportion of the effect mediated through SVR by causal mediation analysis using R. C_LI DiscussionWe will use the German Institute of Quality and Efficiency in Health Care (IQWiG) criterion for surrogacy for cancer and at least 50% of the treatment effect mediated through SVR but will report the information in a way that allows people to interpret the information using their own criteria.

BackgroundAdequate bowel preparation is one of the most important prerequisite during the colonoscopy. It is conductive to detect the polypus, adenoma and early colorectal carcinoma and decrease the rate of overuse of medical resource. BianShi Moxibustion(BSM) is one of the most important Traditional Chinese Medicine(TCM) treatment options, which is called TCM proper technology. BSM is applied to prevent and cure digestive system disorder widely, including functional constipation(FC), irritable bowel syndrome(IBS), functional dyspepsia(FD) etc. we speculate that BSM can improve the bowel preparation quality through ameliorating the function of digestive tract, especially in high risk of inadequate bowel preparation patients, including elderly individual, diabetes mellitus, neurodegenerative changes etc. Hence, the objective of this research is to evaluate the efficacy of BSM on the quality of bowel preparation before colonoscopy. MethodThis is a randomized triple-blinded, single-center, prospective study. We will recruit 72 inpatients who are scheduled to undergo colonoscopy for screening and diagnostic or therapeutical purposes for the first time will be randomized to assign into treatment group or control group at a ratio of 1:1. The intervention plan in the treatment group consists of 3L polyethylene glycol(PEG) solution plus BSM(Treatment period is 3 days, Qd). In the control group, the plan is 3L PEG plus sham BSM. Boston Bowel Preparation Scale(BBPS) will be used to evaluate the efficacy of the bowel preparation and regarded as the primary outcome measure. The secondary outcomes including caecal intubation rate, the willingness to repeat colonoscopy, the tolerance of bowel preparation regimens, the rate of adverse events. DiscussionThe aim of this clinical trial is to confirm the influence of BSM on the quality of bowel preparation. The hypothesis of this study is that the BSM has a positive role on the quality of bowel preparation. The routine bowel preparation regime combines with TCM proper technology will enhance bowel preparation quality and ameliorate the subjective feeling of participants. In addition, it will provide the reliable evidence of bowel preparation prior to colonoscopy from the point of view of integrative medicine. Trial registrationThis protocol and trial was registered in the Chinese Clinical Trial Registry(ChiCTR2300077168).

BackgroundMetabolic-associated fatty liver disease (MAFLD) is a prevalent chronic liver condition with limited approved pharmacological treatments [1]. Ursodeoxycholic acid (UDCA) and ademetionine show variable efficacy, primarily on liver enzymes. This study presents a preliminary analysis comparing the efficacy of a novel dietary supplement, Gepaktiv, against these comparators in MAFLD patients. MethodsIn this open-label, randomized controlled trial (clinicaltrials.gov NCT07068191 and ITMCTR 2025001469), 19 patients with MAFLD, confirmed by hepatomegaly (liver size [&ge;]3 cm above normal by ultrasound), elevated alanine aminotransferase (ALT, 90-150 U/L), and FibroScan results (steatosis [&ge;]260 dB/m, fibrosis [&ge;]11 kPa), were allocated to Gepaktiv (n=6, 1500 mg/day), UDCA (n=7, 10 mg/kg/day), or Ademetionine (n=6, orally 400 mg 2 times a day) for 15 days. Patients with significant alcohol consumption (>20 g/day for women, >30 g/day for men) were excluded. Primary outcomes were median changes from baseline to day 15 in ALT, aspartate aminotransferase (AST), liver size (craniocaudal diameter, cm, via ultrasound), steatosis (controlled attenuation parameter, CAP, dB/m), and fibrosis (transient elastography, kPa). ResultsThe Gepaktiv group showed median [IQR] reductions of ALT -48.9 [-54.0 to -35.0] U/L, AST - 62.8 [-66.0 to -44.0] U/L, liver size -1.9 [-2.0 to -1.2] cm, and steatosis -32.5 [-45.0 to -30.0] dB/m. These reductions were significantly greater compared to both UDCA and Ademetionine groups (p < 0.01 for ALT, AST, and liver size; p < 0.05 for steatosis). Fibrosis reduction was minimal and not statistically significant between groups. ConclusionThe Gepaktiv group was associated with greater improvements in biochemical and imaging markers of MAFLD compared to UDCA and Ademetionine in this preliminary analysis. These findings warrant further investigation in larger, long-term trials. Note: These preliminary results have not been peer-reviewed and should not guide clinical practice.

BackgroundProcess evaluations conducted alongside clinical trials can improve understanding of treatment fidelity and provide contextual knowledge to aide interpretations of trial outcomes. We adopted a multiple-goals perspective to investigate treatment fidelity in two related pilot clinical trials of an adjuvant treatment for pediatric-onset Inflammatory Bowel Disease. This included a focus on barriers and enablers of performing trial-specific activities and of integrating those activities into daily life. MethodsWe interviewed a sub-sample of participants of the Resistant Starch in Pediatric Inflammatory Bowel Disease (NCT04522271) and Optimized Resistant Starch in Inflammatory Bowel Disease pilot trials (NCT04520594) and their caregivers (N=42). The trials examined the effects of personalized food-derived resistant starches as an adjuvant therapy on intestinal microbiome functioning. Codes were identified inductively though conventional content analysis and then mapped to personal projects units of analysis, to explore how participants navigated between activities. ResultsThree themes were identified. The first described the potential impact of living with inflammatory bowel disease and taking prescribed medications. The second described characteristics of trial-specific activities that might impact on their enactment, including perceived difficulty, and challenges following procedures or using trial materials. The third described the integration of trial-specific activities with school, work, household demands, and social, and extracurricular activities. ConclusionsAdjusting to living with inflammatory bowel disease and managing its treatment can impact trial participation. Integrating trial-related activities into daily life can be challenging, which could heighten perceptions of goal conflict. Findings can inform interpretations of trial outcomes and development of strategies for trial optimization and implementation of the adjuvant therapy into clinical practice.

BackgroundWhether extracorporeal CPR (eCPR) has survival benefits over conventional CPR (cCPR) in patients with refractory out-of-hospital cardiac arrest is an unresolved clinical question. Performing trials in this environment is exceedingly challenging and inferences need careful examination. ObjectiveDetermine if a Bayesian perspective provides additional inferential insights. MethodsThe INCEPTION trial of patients with refractory out-of-hospital cardiac arrest reported eCPR and cCPR had similar effects on the primary outcome, 30 day survival with a favorable neurologic outcome. Herein the probability of eCPR superiority, equivalence or inferiority to cCPR is re-evaluated with a Bayesian analysis using both vague and informative priors (from previously completed randomized clinical trials (RCTs)). ResultsDepending on the chosen prior, the Bayesian reanalysis of the INCEPTION intention-to-treat (ITT) data suggests an equivalence probability < 10% (defined as an absolute risk difference (RD) < 1%) but a clinical superiority probability of 66 - 99 % (defined as RD > 1.0). An INCEPTION per protocol (PP) analysis with a vague prior suggested a 1% probability of clinical benefit but this posterior probability increased to 86% when informative PP data from previous RCTs were considered. ConclusionBayesian INCEPTION trial re-analyses provide additional quantative insights. The totality of the ITT evidence reveals a high probability for a clinically meaningful eCPR benefit over cCPR at 30 days. A PP analysis shows a less definitive probability of benefit. (Abstract word count 197, Manuscript word count 1477)

Music engages sensory, motor, cognitive, and emotional systems, making it a powerful model for studying experience-dependent neuroplasticity. Although research on music-related brain changes is expanding, integration of structural, functional, and cerebrovascular findings remains limited, and effects on higher-order cognitive processes remain unclear. This systematic review will synthesize evidence on music-induced cortical adaptations, including structural changes (e.g., gray and white matter alterations), functional modifications in neural networks, and cerebrovascular dynamics, Associations with behavioral outcomes such as attentional control, executive functioning, language processing and emotional processing across the adult lifespan (18+) will also be examined The protocol follows PRISMA and PRISMA-P guidelines and will be prospectively registered with PROSPERO. Searches will be conducted across PubMed, Scopus, Web of Science, PsycINFO, EMBASE, CENTRAL, and Google Scholar, supplemented by citation tracking of relevant reviews. Eligible studies will include randomized and non-randomized intervention trials and observational designs (longitudinal, case-control, cross-sectional). Primary outcome will be focused on musics effects on brain structure and activity. Functional and behavioral measures will be analyzed as secondary endpoints. Data extraction and risk of bias assessment will be performed independently by two reviewers using validated instruments (RoB 2.0, ROBINS-I, ROBINS-E, STROBE, and NHLBI tools). A narrative synthesis will be conducted in accordance with SWiM guidelines, with meta-analyses undertaken where appropriate. Certainty of evidence will be assessed using GRADE scale. Collectively, this protocol establishes a rigorous framework to systematically evaluate how music shapes the brains structure, function, and vascular systems, and how these changes translate into cognitive and behavioral outcomes.