Trials最新文献

{"title":"Co-Boost: boosting and guiding neuroplasticity by combining ketamine with neurofeedback-assisted learning-towards an individualised and integrated pharmaco-psychotherapy for cocaine addiction: study protocol for a randomised, placebo-controlled, double-blind, parallel-group, single-centre trial.","authors":"Anna S Trippel, Ladina P Gubser, Etna J E Engeli, Jan Conradi, Amelie Haugg, Niklaus Zoelch, Marcus Herdener","doi":"10.1186/s13063-025-08982-9","DOIUrl":"10.1186/s13063-025-08982-9","url":null,"abstract":"<p><strong>Background: </strong>Cocaine is the most frequently used stimulant worldwide, with increasing consumption rates in Europe. Cocaine use is associated with great harm to individuals and society. As of today, psychotherapeutic interventions for cocaine use disorder (CUD) demonstrate only modest effect sizes, and no pharmacotherapy has been approved due to gaps in understanding the disease. However, a novel pharmacotherapeutic target, i.e. glutamatergic neurotransmission, emerged from animal models of addiction. Specifically, after chronic cocaine administration, glutamate concentrations in the nucleus accumbens (NAcc) of rodents are reduced, while there is an overflow of glutamate during cue-induced cocaine-seeking. Recently, this glutamatergic imbalance has also been observed in humans with CUD. Additionally, promising findings with regard to novel psychotherapeutic approaches came from neurofeedback training (NFT) studies where participants use cognitive strategies to regulate their activity within a specific brain region based on \"real-time\" feedback about its activity as assessed by real-time functional magnetic resonance imaging (rt-fMRI). For example, participants with CUD successfully learned to regulate their brain activity in reward areas of the midbrain using reward imagery and to reconstitute reward sensitivity to non-drug related reinforcers like, e.g. social interactions, athletic or professional achievements. We therefore investigate the therapeutic potential and the underlying mechanisms of two interventions, a single dose of ketamine and a reward imagery rt-fMRI NFT in 120 participants with CUD.</p><p><strong>Methods: </strong>We examine a single ketamine infusion, three sessions of reward imagery rt-fMRI NFT, and the combination of those interventions contrasted to a placebo infusion or a sham NFT in 120 participants with CUD. The study is designed in a randomized, placebo-controlled, double-blind fashion with four study arms.</p><p><strong>Discussion: </strong>We expect both interventions to have a positive effect on the proportion of cocaine use days. We predict glutamate levels in the reward system to increase with the ketamine infusion and to reduce craving, a re-enhanced sensitivity towards natural rewards resulting from the rt-fMRI NFT, and synergistic effects of the combined interventions. This neurobiologically informed approach has the potential to open new avenues for the treatment of CUD through individualised and integrated pharmaco-psychotherapy.</p><p><strong>Trial registration: </strong>NCT06125054 ClinicalTrials.gov. Registered on October 26, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"354"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engaging English- and Spanish-speaking older adults with and without possible cognitive impairment in advance care planning group visits: protocol for the ENgaging in Advance Care Planning Talks (ENACT) randomized controlled trial.","authors":"Samantha A Farro, Elizabeth Juarez-Colunga, Chandni Patel, Brianne M Bettcher, Christine A Haynes, Amy G Huebschmann, David Nowels, Caroline K Tietbohl, Jiayuan Shi, Carly Ritger, Prajakta Shanbhag, Kathleen Resman, Rebecca L Sudore, Hillary D Lum","doi":"10.1186/s13063-025-08964-x","DOIUrl":"10.1186/s13063-025-08964-x","url":null,"abstract":"<p><strong>Background: </strong>Advance care planning (ACP) helps patients identify and communicate their preferences for medical care and prepares them for decision-making related to future care. While ACP is recommended for older adults with cognitive impairment, few interventions have been tested in primary care for this population. The ENACT trial tests the efficacy of the ENgaging in Advance Care planning Talks (ENACT) Group Visits intervention, which engages older adults with and without possible cognitive impairment in group medical visits focused on the ACP process.</p><p><strong>Methods: </strong>This two-arm randomized trial compares the efficacy of the ENACT Group Visits intervention arm to a control arm at 6-month follow-up. The trial will enroll at least 480 patients across 8 primary care clinics. Notable inclusion criteria include English or Spanish-speaking, age 70 or older, and no ACP documents in the electronic health record (EHR) in the past 2 years. The Montreal Cognitive Assessment screener will be administered at study enrollment to identify whether the participant has possible cognitive imparment. Participants will be randomized 1:1 to the ENACT Group Visits arm or control arm. The ENACT Group Visits intervention entails two group visits, facilitated by multidisciplinary clinic staff. The control arm entails sending ACP materials via mail. The primary outcome is new documentation of ACP in the EHR at 6-month follow-up, and it will be analyzed using logistic regression with random effects for site. Secondary outcomes include patient-level ACP readiness, decision self-efficacy, and quality of communication. The impact of possible cognitive impairment on ENACT intervention efficacy will be examined. Survival analyses will be used to examine time-to-new ACP documentation. Mixed methods, including multiple qualitative methods, will be used to assess acceptability, feasibility, intervention fidelity, and other implementation outcomes of the ENACT intervention among patients with possible cognitive impairment.</p><p><strong>Discussion: </strong>This study will determine the efficacy of the ENACT Group Visits intervention among diverse older adults, including those with possible cognitive impairment, as evidenced by increased documentation of ACP in the medical record. If efficacious, primary care clinics may implement this ACP intervention that leverages peer interactions and goal setting to support a person-centered ACP process.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov: NCT05421728. Registered on 13 June 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"353"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sedation-related adverse events in gastrointestinal endoscopy (CH-ESC study): study protocol for a prospective, observational cohort study in a Chinese tertiary hospital.","authors":"Jun Lu, Bo Li, Shushu Yan, Yu Deng, Yu Guo, Boyang Xia, Yueying Wang, Lulong Bo","doi":"10.1186/s13063-025-09107-y","DOIUrl":"10.1186/s13063-025-09107-y","url":null,"abstract":"<p><strong>Background: </strong>Sedation is commonly employed during gastrointestinal endoscopy (GIE), yet sedation-related adverse events (SRAEs)-particularly cardiopulmonary complications-remain a critical safety concern. While large cohort studies from Western countries have identified key risk factors such as advanced age, obesity, and high ASA classification, data on SRAEs within the Chinese population are scarce. This study aims to assess the prevalence, characteristics, and risk factors associated with SRAEs in a Chinese tertiary hospital setting.</p><p><strong>Methods/design: </strong>This prospective, observational cohort study is being conducted at the Changhai Digestive Endoscopy Center, one of the largest GIE facilities in China. Between November 2023 and November 2026, we aim to recruit 100,100 patients undergoing sedated GIE. The primary outcome is the incidence of SRAEs during the endoscopy procedure. Comprehensive data on patient demographics (e.g., age, BMI), sedation parameters (e.g., medications used, sedation depth), and endoscopic procedure specifics (e.g., type and duration) will be collected, and these candidate factors will be entered into multivariate logistic regression analysis to identify independent predictors of SRAEs.</p><p><strong>Discussion: </strong>With the increasing application of sedation during GIE, preventing and managing SRAEs is of paramount importance. The outpatient nature and short duration of these procedures complicate accurate reporting, potentially leading to an underestimation of SRAEs. Beyond established risk factors, this study seeks to explore emerging predictors, including waist-to-hip ratio and frailty assessments. Although this is a single-center study, it represents the first large-scale investigation of SRAEs in China and may contribute to improved risk stratification models and enhanced patient safety protocols.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Register, ChiCTR2300078784. Registered on December 18, 2023.</p><p><strong>Study status: </strong>Recruitment began on December 1, 2023. As of July 31, 2024, 6023 participants have been enrolled. The study team plans to request an extension from the Ethics Committee to continue enrolment until December 31, 2028.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"356"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the effect of a cognitive-behavioral therapy intervention aimed at reducing weight self-stigma on adherence to weight loss diet and anthropometric indices in adult women with obesity: study protocol for a randomized controlled trial.","authors":"Mohammad Salar Fahami, Amir Hossein Lame-Jouybari, Mahdieh Abbasalizad-Farhangi","doi":"10.1186/s13063-025-09113-0","DOIUrl":"10.1186/s13063-025-09113-0","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a complex and chronic condition with serious health risks, including higher chances of diabetes, heart disease, and certain types of cancer. Weight self-stigma, prevalent among individuals with obesity, exacerbates psychological distress and negatively impacts adherence to weight loss diets. Cognitive-behavioral therapy (CBT), a psychological intervention targeting maladaptive beliefs and behaviors, has shown promise in addressing weight self-stigma. However, the specific impact of CBT, delivered in a group therapy format, on adherence to prescribed weight-loss diets has not yet been adequately investigated, particularly among women with obesity, who are disproportionately affected by both the condition and weight self-stigma.</p><p><strong>Methods: </strong>This research is a two-arm, parallel-group randomized controlled trial aimed at assessing the effectiveness of a group-based CBT intervention in mitigating weight self-stigma and enhancing adherence to a weight-loss diet and anthropometric outcomes in adult women with obesity. Participants (n = 120) who meet the inclusion criteria will be randomly allocated to one of two groups: (1) CBT in addition to a personalized weight-loss diet, or (2) only the personalized weight-loss diet. The CBT intervention will consist of 1.5-h weekly online group therapy sessions over 12 weeks. Outcome assessments, including adherence to the weight loss diet and changes in anthropometric measures (fat-free mass (FFM), fat mass (FM), and body mass index), will be performed at baseline and 4, 8, and 12 weeks. Adherence will be assessed based on changes in FM and FFM to avoid reliance on self-reported data. Additional assessments will include scores from validated psychological and health-related questionnaires, including the Weight Self-Stigma Questionnaire, the Weight Bias Internalization Scale, and the General Health Questionnaire.</p><p><strong>Discussion: </strong>This study aims to clarify its role in improving dietary adherence and weight management outcomes by addressing weight self-stigma through a CBT intervention. If successful, the findings could inform healthcare strategies and contribute to developing comprehensive interventions for obesity management. The study is expected to provide evidence for integrating psychological support into weight loss programs, particularly for populations most affected by stigma. We suggest that this trial has the potential to refine therapeutic approaches for weight management in women with obesity.</p><p><strong>Trial registration: </strong>IRCT20140907019082N12 Registered on November 25, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"343"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimands in equivalence trials and non-inferiority trials: a cross-sectional study of EMA scientific advice to drug developers.","authors":"Jonathan Bergman, Lorenzo Guizzaro, Juan Jose Abellan, Florian Lasch","doi":"10.1186/s13063-025-09068-2","DOIUrl":"10.1186/s13063-025-09068-2","url":null,"abstract":"<p><strong>Background: </strong>The Estimands framework, introduced in the Addendum to ICH E9, provides a structured method to define treatment effects in clinical trials. The main novelty of the framework is the discussion of intercurrent events as part of the treatment effect definition. It is widely believed that the application of the framework to non-inferiority and equivalence trials deserves specific consideration.</p><p><strong>Methods: </strong>To examine the current practices of using the estimand framework in non-inferiority and equivalence trials, we reviewed the scientific advice provided by the European Medicines Agency to drug developers in 2022. This review aimed to determine how often the estimands framework is used by drug developers and/or recommended by EMA and to describe what intercurrent events and handling strategies are being proposed by drug developers and recommended by EMA.</p><p><strong>Results: </strong>The use of the framework varied substantially by clinical development phases. While it was used for phase 3 trials in 47% (25/53) by developers, it was used in 5% (1/19) of the phase 1 trials. For 39% (11/28) of the trials where developers did not use the estimands framework in phase 3, there was no regulatory recommendation to adopt the framework in the response. The most discussed intercurrent event in our sample was 'treatment discontinuation' (n = 47), for which developers most often proposed either a treatment policy strategy (17/47, 36%) or a hypothetical strategy (11/47, 23%). In contrast, EMA most often recommended the use of two co-primary estimands with two different strategies (22/47, 47%).</p><p><strong>Conclusions: </strong>Generally, the proposed and recommended strategies depend on the clinical setting and the respective intercurrent event. Developers almost always proposed a single primary estimand, whereas EMA often recommended two co-primary estimands differing in the strategies used to handle some or all the intercurrent events. Further interaction between academia, industry and regulators is necessary to progress the implementation process of the estimands framework for non-inferiority and equivalence trials.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"348"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of soluble dietary fiber on glycolipid metabolism in gestational diabetes mellitus: study protocol for a randomized controlled clinical trial.","authors":"Yiming Wang, Huacai Yuan, Ruyue Jiang, Keqing Jia, Xiaoping Ding, Ping Gu, Jianping Sun","doi":"10.1186/s13063-025-09080-6","DOIUrl":"10.1186/s13063-025-09080-6","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence suggests that additional dietary fiber supplements may significantly improve glycolipid metabolism and pregnancy outcomes in individuals with gestational diabetes mellitus (GDM). However, the therapeutic effects of xylose oligosaccharides and inulin (XOS inulin) in pregnant women have not been investigated. Moreover, the underlying mechanism behind the therapeutic effects of this type of dietary fiber is not clear. Our study aims to assess the effects of daily XOS inulin supplementation on glycolipid metabolism and elucidate the therapeutic mechanism through gut microbiota analysis.</p><p><strong>Methods: </strong>This study is an 8-week, parallel-design, open-label, three-arm, single-center randomized controlled trial. Eligible participants were pregnant women between 24 and 28 weeks of gestation, and they were diagnosed with GDM through an oral glucose tolerance test (OGTT). The participants in the three groups will receive nutrition education alone, nutrition education plus XOS inulin (XOS 2 g and inulin 10 g) 12 g/day, or nutrition education plus XOS inulin 24 g/day. Measurements will be taken at baseline, week 4, and week 8. The primary outcome will be the change in glycosylated serum protein (GSP), and the key secondary outcomes include changes in fasting glucose, fasting insulin (FINS), 2-h postprandial plasma glucose (2 h-PPG), HbA1c, total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and changes in the gut microbiota.</p><p><strong>Discussion: </strong>This study will evaluate the therapeutic effects of XOS inulin supplementation on glycemic control, lipid metabolism, gastrointestinal function, and perinatal outcomes in GDM patients and their offspring. It also provides insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for GDM. All participants will receive comprehensive GDM nutrition education, promoting sustainable dietary modifications that optimize maternal metabolic health and fetal outcomes.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial registry ChiCTR2200060117. Registered on 19 May, 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"349"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifidobacterium treatment for chronic low back pain in patients with Modic changes: study protocol for a multicenter, randomized, placebo-controlled trial.","authors":"Sunqi Nian, Chengjin Li, Na Li, Fei Chen, Caiwang Zhao, Guangyao Zhang, Sheng Lu, Jiayu Chen","doi":"10.1186/s13063-025-09084-2","DOIUrl":"10.1186/s13063-025-09084-2","url":null,"abstract":"<p><strong>Background: </strong>Low back pain (LBP) is a major global health issue, affecting approximately two-thirds of the population at some point in their lives. Modic changes (MCs) in the vertebral endplates, as observed on MRI, are recognized contributors to LBP and may be linked to advanced stages of intervertebral disc degeneration (IDD). Prior research has shown a decrease in the genus Bifidobacterium in the endplate cartilage of patients with IDD and concurrent MCs. The potential link between reduced Bifidobacterium levels and MC-related LBP remains unclear.</p><p><strong>Methods: </strong>This multicenter, double-blinded, randomized, placebo-controlled trial will be conducted at four hospitals in China, comparing the efficacy of orally administered Bifidobacterium adolescentis (BA) with that of a placebo. Participants will receive the treatment twice daily for a duration of three months. The study targets patients with chronic low back pain (LBP) and Modic type I or II. Eligible patients will be randomly assigned to receive either Bifidobacterium adolescentis or a placebo for three months. The primary outcome will be the change in the Simplified Chinese Roland-Morris Disability Questionnaire (SCRMDQ) score at 3, 6, and 12 months post-treatment. Secondary outcomes include changes in DASS-21 scores, MRI imaging, bone density measurements, and serum biomarker analysis.</p><p><strong>Discussion: </strong>This study will provide valuable insights into the therapeutic potential of Bifidobacterium adolescentis in managing chronic LBP associated with Modic changes, potentially offering a novel approach to treating this common and debilitating condition.</p><p><strong>Trial registration: </strong>The trial has been registered with China Clinical Trial Registry, under the registration number ChiCTR2400088577. Registered on 21 August. The study was prospectively registered.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"347"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IC3 trial: protocol for a multicentre individually randomised controlled trial to compare a cirrhosis detection and hepatocellular carcinoma surveillance pathway vs usual care in Australian general practice for 45-75 years old with risk factors for chronic liver disease.","authors":"Leon A Adams, Deborah de Guingand, Gary P Jeffrey, Alexander J Thompson, Simone I Strasser, Darrell Crawford, Louisa Collins, Christopher Reid, Michael Wallace, Patty Chondros, Nicole Allard, Andrew Kirke, Claudia Rutherford, Charlotte Hespe, Riitta Partanen, Sophie Frear, Holly Napreet, Katerina Piakis, Cailin Maas, Olivia J White, Adrian Laughlin, Tara Clinton-McHarg, Caitlin Clymer, Lucy Boyd, Jon Emery","doi":"10.1186/s13063-025-09037-9","DOIUrl":"10.1186/s13063-025-09037-9","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) incidence and mortality rates are increasing at a greater pace than any other cancer in Australia. Cirrhosis is the major risk factor for HCC, and early detection of HCC through surveillance of people with cirrhosis can improve outcomes. However, cirrhosis is under-detected in primary care settings, with 60% of patients diagnosed with HCC having unrecognised cirrhosis and not found to be in a surveillance programme. Targeted screening of at-risk populations in primary care using noninvasive tests for liver fibrosis could lead to improved diagnosis of cirrhosis and increased participation in HCC surveillance programmes.</p><p><strong>Methods: </strong>This is a prospective multicentre parallel randomised controlled trial of 2470 participants, to evaluate the impact of a cirrhosis detection and hepatocellular carcinoma surveillance pathway compared to usual care in 45-75 year olds, with risk factors for chronic liver disease, from regional and urban general practice clinics, across four Australian states. Participants will be randomised 1:1, to usual general practitioner care (control) or a cirrhosis detection pathway (intervention), stratified by clinic and potential hazardous drinking. The cirrhosis detection intervention consists of liver fibrosis blood tests (comprising the Fibrosis-4 Index and Hepascore) and a liver stiffness measurement conducted by FibroScan in those with elevated liver fibrosis blood markers. Participants with elevated FibroScan® values will be recommended for referral for hepatology assessment to determine the need for HCC surveillance. The primary outcome is the between-arm difference in proportion of participants with newly diagnosed cirrhosis in HCC surveillance at 12 months. Secondary outcomes at 12 months will include the between-arm difference in proportion of participants with a diagnosis of any stage HCC, diagnoses of advanced fibrosis and liver decompensation and mean anxiety state and mean quality of life. The cost-effectiveness of the cirrhosis detection pathway will be determined using data linkage to state and national health datasets. Process evaluation will involve assessment of the optimal cirrhosis detection pathway, along with the barriers and enablers of implementation of this pathway, assessed by participant interviews.</p><p><strong>Discussion: </strong>This trial will provide evidence of the efficacy and cost-effectiveness of a cirrhosis detection pathway in Australian general practice settings. This will provide evidence to guide the early identification and appropriate placement of patients in HCC surveillance programmes, resulting in earlier HCC diagnosis and improved outcomes.</p><p><strong>Trial registration: </strong>Australian and New Zealand Clinical Trial Registry ACTRN12622000185763p. Registered on 3rd February 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"350"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeine to improve neurodevelopmental outcomes in infants born late preterm (The Latte Trial): study protocol for a randomised controlled trial.","authors":"Jane M Canning, Christopher J D McKinlay, David G McNamara, Liza K Edmonds, Jenny A Rogers, Braden Te Ao, Alana Cavadino, Elizabeth A Oliphant, Jane M Alsweiler","doi":"10.1186/s13063-025-09029-9","DOIUrl":"10.1186/s13063-025-09029-9","url":null,"abstract":"<p><strong>Background: </strong>Late preterm infants (34⁺⁰ to 36⁺⁶ weeks' gestation) account for 7% of births in well-resourced nations. In Aotearoa New Zealand, Māori (Indigenous peoples) make up 20% of late preterm births. Late preterm infants are at higher risk of adverse outcomes, including mortality, cerebral palsy and cognitive impairment. Yet, there has been little focus on prophylactic interventions to address these risks. Late preterm infants have more frequent episodes of intermittent hypoxaemia than term infants in the first few postnatal weeks. Caffeine citrate, a routine intervention for apnoea of prematurity in extremely preterm infants, improves long-term neurodevelopmental outcomes in very low birth weight infants and reduces the incidence of intermittent hypoxaemia in late preterm infants. The Latte Trial aims to determine whether prophylactic caffeine citrate given to late preterm infants from birth to term corrected age improves neurodevelopmental outcomes.</p><p><strong>Methods: </strong>This phase III multi-centre, parallel two-arm, double-blind, placebo-controlled randomised superiority trial will randomise 478 late preterm infants or twin pairs to receive caffeine citrate (loading dose 40 mg.kg^-1, then 20 mg.kg^-1 daily) or placebo until 40⁺⁰ weeks' postmenstrual age. There is an intentional focus on the recruitment of infants of Māori ethnicity to aspire to Mana Whakamārama (equal explanatory power for the Māori population) given their over-representation in late preterm births. Randomisation will be stratified by centre, gestation at birth (34, 35 or 36 completed weeks) and ethnicity (Māori or non-Māori). The primary outcome is the Bayley Scales of Infant Development 4th Edition cognitive score at 2.5 years' corrected age. Primary analysis will be performed on a modified intention-to-treat basis, comparing outcomes between intervention groups using generalised mixed models with adjustment for stratification, potential confounding by socio-economic status and sex, and non-independence of multiples (random effect).</p><p><strong>Discussion: </strong>Of early developmental domains, cognition is the most predictive of later neurodevelopmental outcome and intelligence quotient. Prioritisation of the Indigenous population within trials is important. If prophylactic caffeine citrate is found to improve neurodevelopment in late preterm infants, this could have a significant impact on the long-term quality of life and health and wellbeing of this large population of infants.</p><p><strong>Trial registration: </strong>ANZCTR ACTRN12622001344785. Registered on 19 October 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"346"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrawound vancomycin powder for prevention of surgical site infections after open instrumented posterior spinal fusion (VANCO Trial)-methodology of a randomized, controlled, multicenter study.","authors":"Ralph T Schär, Mattia Branca, Urs Fischer, Stefan Zimmerli, Nicole Söll","doi":"10.1186/s13063-025-09095-z","DOIUrl":"10.1186/s13063-025-09095-z","url":null,"abstract":"<p><strong>Background: </strong>Surgical site infections (SSIs) after instrumented spine fusion surgery may occur in up to 12% of cases and lead to increased morbidity, mortality, and healthcare costs. Numerous retrospective studies suggest the use of intrawound vancomycin powder in spine surgery to be protective against SSIs. The use of intrawound vancomycin powder is controversial, and there is a paucity of well-designed prospective trials evaluating its safety and efficacy in spine surgery. The objective of the VANCO Trial is to evaluate the safety and efficacy of intrawound vancomycin powder in open instrumented spine fusion surgery to prevent SSIs.</p><p><strong>Methods: </strong>The VANCO Trial is a multicenter, 1:1 randomized superiority trial with a total of 7 recruiting spine institutions in Switzerland. Adult patients scheduled for an open spinal fusion procedure will be screened for eligibility. Randomization of participants will take place intraoperatively before wound closure. Patients randomized into the treatment arm will receive 1-2 g of vancomycin powder (depending on length of skin incision: ≤ 20 cm vs. > 20 cm), which will be administered above the closed muscle fascia (suprafascially-subcutaneously) before wound closure. The main outcome and measure is the rate of superficial and deep SSIs within 90 days following surgery.</p><p><strong>Discussion: </strong>The VANCO Trial is one of the first clinical trials to evaluate the safety and efficacy of intrawound vancomycin powder in a selected spine surgery population. Routine administration of intrawound vancomycin powder in selected spine surgery patients could fundamentally advance international standards for reducing SSIs.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT04017468.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"344"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}