Trials最新文献

{"title":"Statistical documentation for multi-disease, multi-domain platform trials: our experience with the Staphylococcus aureus Network Adaptive Platform trial.","authors":"Robert K Mahar, Anna McGlothlin, Michael Dymock, Lauren Barina, Marc Bonten, Asha Bowen, Matthew P Cheng, Nick Daneman, Anna L Goodman, Todd C Lee, Roger J Lewis, Thomas Lumley, Alistair R D McLean, Zoe McQuilten, Jocelyn Mora, David L Paterson, David J Price, Jason Roberts, Tom Snelling, Jonas Tverring, Steve A Webb, Dafna Yahav, Joshua S Davis, Steven Y C Tong, Julie A Marsh","doi":"10.1186/s13063-024-08684-8","DOIUrl":"10.1186/s13063-024-08684-8","url":null,"abstract":"<p><p>Platform trials have become widely adopted across multiple disease areas over recent years, however, guidelines for operationalising these trials have not kept pace. We outline a series of documents that summarise the statistical components, and implicit processes, of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial to provide an informal template for other researchers and reviewers of platform trials. We briefly summarise the content and role of the core protocol, statistical appendix, domain-specific appendices, simulation report, statistical implementation guides, data safety and monitoring committee (DSMC) reports, and domain-specific statistical analysis plans and final reports, and a transparent governance structure that ensures separate blinded and unblinded statistical teams. In the absence of guidelines or checklists for platform trial statistical documents, we hope to provide useful guidance to others in terms of what has worked so far for the SNAP trial, stimulate discussion, and inform a future consensus.Trial registration NCT05137119 . Registered on 30 November 2021.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"49"},"PeriodicalIF":2.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400303","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":"Comparison of the effects of transcranial direct current stimulation and transcutaneous tibial nerve stimulation on the urgency and frequency of women with overactive bladder syndrome: study protocol of a randomized clinical trial.","authors":"Zahra Gorji, MohammadReza Hadian Rasanani, Michael Nitsche, Tannaz Ahadi, Roya Khanmohammadi, Mona Gorji, Roxana Bazaz Behbahani, Vahid Rafiei Manesh","doi":"10.1186/s13063-025-08738-5","DOIUrl":"10.1186/s13063-025-08738-5","url":null,"abstract":"<p><strong>Background: </strong>Overactive bladder syndrome is common, with a prevalence of 12-17% among adults. Posterior tibial nerve stimulation is the primary nonpharmacological and conservative treatment for overactive bladder syndrome. While several human brain imaging studies have shown the involvement of supraspinal centers in bladder control, a literature review has found that no research has specifically investigated cortical stimulation through transcranial direct current stimulation as a treatment for overactive bladder syndrome in women. Therefore, this study aims to assess the potential benefits of transcranial direct current stimulation (tDCS) and compare them with the effects of posterior tibial nerve stimulation on overactive bladder syndrome.</p><p><strong>Methods/design: </strong>The random allocation method will be used to divide the participants into two groups. Group 1 (n = 19) will undergo pelvic floor muscle training and transcutaneous tibial nerve stimulation. Group 2 (n = 19) will undergo pelvic floor muscle training and transcranial direct current stimulation. The transcranial direct current stimulation for group 2 will consist of 12 sessions occurring thrice a week, each lasting for 20 min. Anodal tDCS will be administered to FPz targeting the medial prefrontal cortex (mPFC) for 12 sessions, with the cathode electrode positioned between Oz and inion at an intensity of 2 mA for 20 min.</p><p><strong>Discussion: </strong>It is believed that utilizing an approach involving non-invasive electrical stimulation of the cortex could lead to a more efficient treatment for individuals with overactive bladder. Additionally, it is theorized that combining the effects of tDCS and pelvic floor muscle training could present an innovative technique for alleviating the negative impacts of overactive bladder syndrome. Ultimately, this new method could provide help for patients who have not responded to conventional therapy.</p><p><strong>Trial registration: </strong>Iranian Registry of Clinical Trials (IRCT) ID: IRCT20090301001722N26, registration date: May 17, 2023. https://en.irct.ir/ .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"48"},"PeriodicalIF":2.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383074","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 monitoring dietary biomarkers and providing vegetable juice on metabolic syndrome components in adults with an overweight or obese body mass index in Ulaanbaatar: a randomized controlled trial.","authors":"Erina Tamaru, Yusuke Ushida, Hiroyuki Suganuma, Bayasgalan Jambaldorj, Oyundelger Dechinjamts, Tuvshinbayar Bayaraa, Tuul Bayarmagnai, Batjargal Jamiyan, Narantuya Davaakhuu, Suvd Batbaatar, Unursaikhan Surenjav, Narmisheekh Khasag","doi":"10.1186/s13063-024-08712-7","DOIUrl":"10.1186/s13063-024-08712-7","url":null,"abstract":"<p><strong>Background: </strong>Mongolian people have traditionally had poor vegetable intake habits, which is a cause of increasing prevalence of metabolic syndrome. Monitoring vegetable intake through the dietary biomarkers such as skin carotenoid level, and urinary sodium-to-potassium (Na/K) ratio (represents intake status of salt and vegetable), has been recently suggested to be useful to improve dietary habits. Vegetable juices are an easy way to consume vegetable-derived ingredients. This study aimed to examine the following two points in adults with an overweight or obese body mass index (BMI) in Ulaanbaatar; (1) relationships between these dietary biomarkers and metabolic syndrome components, and (2) effects of an intervention combining regular monitoring of these dietary biomarkers and provision of vegetable juices on values of the dietary biomarkers and metabolic syndrome components.</p><p><strong>Methods: </strong>Ninety-four Mongolian adults with BMI ≥ 25 living in Ulaanbaatar were analyzed. (1) Relationships between baseline values of dietary biomarkers and metabolic syndrome components were analyzed by simple correlation and multiple regression analyses. (2) Participants were randomly allocated to control, monitoring, and monitoring + vegetable juice groups. During the 8-week intervention, the monitoring and monitoring + vegetable juice groups were monitored their dietary biomarkers and blood pressure every two weeks, and the monitoring + vegetable juice group was additionally provided with vegetable juice every day. Changes in dietary biomarkers and metabolic syndrome components before and after intervention were compared among the three groups.</p><p><strong>Results: </strong>(1) The skin carotenoid levels were negatively correlated with blood triglyceride levels, whereas the urinary Na/K ratio was positively associated with systolic and diastolic blood pressure. (2) Through the intervention, the monitoring + vegetable juice group showed significant increase in skin carotenoid level (+ 1.72), decrease in urinary Na/K ratio (- 0.80 mol/mol), and decrease in waist circumference (- 2.63 cm) compared to the control group (+ 0.28, + 0.45, and + 0.22, respectively).</p><p><strong>Conclusions: </strong>The combination of the monitoring dietary biomarkers and providing vegetable juice was suggested to be effective in improving dietary habits and metabolic syndrome components including waist circumference in Mongolian adults with an overweight or obese BMI.</p><p><strong>Trial registration: </strong>UMIN-CTR Clinical Trial UMIN000051715 on July 26, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"47"},"PeriodicalIF":2.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383099","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":"Safety reporting in neonatal clinical trials: reflections towards optimal, globally relevant approaches.","authors":"Louise F Hill, Christina W Obiero, Adrie Bekker, Ann Sarah Walker, Julia A Bielicki, Mike Sharland, Francesca Schiavone","doi":"10.1186/s13063-025-08723-y","DOIUrl":"10.1186/s13063-025-08723-y","url":null,"abstract":"<p><p>Adverse event (AE) collection is a key part of evidence generation in clinical trials and an integral element of safety reporting. AE assessment and documentation is particularly challenging in neonates who are a heterogeneous population with high rates of co-morbidities. Neonatal research is finally gaining the attention of regulators regarding drug development and the need for optimal dosing specific to this population. However, further efforts are necessary to ensure that adverse events (AEs) are adequately collected, allowing for the generation of essential safety data. It is also crucial that the methodology used aligns with the intended trial outcomes to minimise the burden on trial sites. In resource-constrained settings, where pharmacovigilance implementation can be particularly challenging, a pragmatic approach to safety reporting is even more important given the significant public health need for effective drugs. This commentary reflects on some of the challenges and potential areas of improvement in safety reporting that could be addressed in future neonatal-focused trials.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"46"},"PeriodicalIF":2.0,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383107","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":"Metformin versus insulin in glycemic control in pregnancy (MevIP): a randomized clinical trial protocol.","authors":"Carolina Freitas Alves Amaral-Moreira, Daiane Sofia Morais Paulino, Belmiro G Pereira, Patricia Moretti Rehder, Fernanda G Surita","doi":"10.1186/s13063-025-08752-7","DOIUrl":"10.1186/s13063-025-08752-7","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes is one of the most prevalent diseases in pregnancy, with an incidence of 5 to 18% in Brazil, and is associated with high morbidity rates. The first-line treatment is insulin, although some recent studies have indicated that metformin might also be effective. Metformin is safe in pregnancy and appears to produce better results than insulin, including reduced gestational weight gain (GWG) and smaller gestational-age newborns. Few studies have been conducted on this topic in low- and middle-income countries.</p><p><strong>Methods: </strong>We designed an open randomized controlled trial comparing two treatments for pregnant women with type II diabetes mellitus (DM) and gestational diabetes (DMG): the metformin group (intervention) and the insulin group (as a routine service). The primary outcome is glycemic control. The secondary outcomes are GWG, the occurrence of hypertensive syndromes, macrosomia, and neonatal hypoglycemia. The sample will comprise 92 pregnant women, 46 per group. The inclusion criteria will be GDM or type II DM requiring medication for glycemic control, singleton pregnancy, and gestational age under 34 weeks. The exclusion criteria will be current treatment with any medication for glycemic control, type I DM, and intolerance to the study medications (metformin or insulin). Women will be routinely followed during antenatal care, childbirth, and the postpartum period. Statistical analyses will include the intention-to-treat approach and a comparison between the two groups.</p><p><strong>Discussion: </strong>Considering the Brazilian socioeconomic reality and the safety of metformin demonstrated in previous trials, we expect that the MevIP study will demonstrate that metformin is an adequate and appropriate medication for GDM treatment in the Brazilian population, representing an alternative to insulin for GDM.</p><p><strong>Trial registration: </strong>This protocol has been registered prospectively in ReBEC under the ID RBR-3j3cktx in August 11, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"45"},"PeriodicalIF":2.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374798","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":"Understanding Cognition, Oxytocin, and Pain in Elders (UCOPE): protocol for a double-blinded cross-over trial in chronic knee osteoarthritis pain.","authors":"Yenisel Cruz-Almeida, Soamy Montesino-Goicolea, Pedro Valdes-Hernandez, Zhiguang Huo, Roland Staud, Natalie C Ebner","doi":"10.1186/s13063-024-08715-4","DOIUrl":"10.1186/s13063-024-08715-4","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is the leading cause of disability among older adults with the knee being the most affected joint. Specifically, there is an urgent need to develop better analgesics for individuals with OA-related pain, since currently used analgesics frequently fail to provide adequate relief or must be discontinued owing to adverse effects. A promising treatment is the neuropeptide oxytocin (OT), which has been shown to play a role in endogenous analgesia with human and animal studies demonstrating anti-nociceptive effects. The primary aims of the study are to examine preliminary analgesic effects of a chronic OT intervention in community-dwelling older individuals with chronic knee osteoarthritis pain.</p><p><strong>Methods: </strong>In this article, we describe the rationale and design of the Understanding Cognition, Oxytocin, and Pain in Elders (UCOPE) study, a double-blinded intervention in which 80 participants over 45 years of age with knee osteoarthritis pain will be recruited to participate in a cross-over trial of 4 weeks of intranasal oxytocin or placebo administration. Primary study outcomes include preliminary changes in pain intensity and interference as well as multi-modal assessment batteries including circulating biomarkers and neuroimaging measures. Self-reported and quantitative outcomes will be assessed at baseline, post-intervention periods, and up to a 6-month follow-up period.</p><p><strong>Discussion: </strong>This study will establish preliminary effectiveness of a novel intervention in middle to older aged adults with knee osteoarthritis pain. Achievement of these aims will provide a rich platform for future intervention research targeting improvements in pain and disability among geriatric populations and will serve as a foundation for a fully powered trial to examine treatment efficacy and potential mechanisms of the proposed intervention.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03878589. Registered on March 18th, 2019.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"44"},"PeriodicalIF":2.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371282","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":"Antisecretory factor in severe traumatic brain injury (AFISTBI): protocol for an exploratory randomized placebo-controlled trial.","authors":"Linus Réen, David Cederberg, Niklas Marklund, Edward Visse, Peter Siesjö","doi":"10.1186/s13063-025-08760-7","DOIUrl":"10.1186/s13063-025-08760-7","url":null,"abstract":"<p><strong>Background: </strong>Despite recent advances in neuroimaging and neurocritical care, severe traumatic brain injury (TBI) is still a major cause of severe disability and mortality, with increasing incidence worldwide. Antisecretory factor (AF), commercially available as Salovum®, has been shown to lower intracranial pressure (ICP) in experimental models of, e.g., TBI and herpes encephalitis. The aim of this study is to assess the effect of antisecretory factors in adult patients with severe TBI on ICP and inflammatory mediators in extracellular fluid and plasma.</p><p><strong>Methods/design: </strong>This is a single-center, randomized, placebo-controlled clinical phase 2 trial, investigating the clinical superiority of Salovum® given as a food supplement during 5 days to adults with severe TBI (Glasgow Coma Scale (GCS) < 9), admitted to the neurocritical intensive care unit (NICU) at Skane university hospital, Lund, Sweden. All patients with GCS < 9 and clinical indication for insertion of ICP-monitor and microdialysis catheter will be screened for inclusion and assigned to either the treatment group (n = 10) or placebo group (n = 10). In both groups, the primary outcome will be ICP (mean values and change from baseline during intervention), registered from high-frequency data monitoring for 5 days. Secondary outcomes will be inflammatory mediators in plasma and intracerebral microdialysis perfusate days 1, 3, and 5 during trial treatment.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT04117672. Registered on September 17, 2017. Protocol version 6 from October 24, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"43"},"PeriodicalIF":2.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371261","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":"Non-inferiority study to compare the efficacy of relugolix with dienogest for endometriosis-associated pain and usefulness of administering relugolix prior to dienogest (READY study): study protocol for a multicenter randomized controlled study.","authors":"Fuminori Taniguchi, Motoko Fukui, Yutaka Osuga, Tasuku Harada, Jo Kitawaki","doi":"10.1186/s13063-025-08750-9","DOIUrl":"10.1186/s13063-025-08750-9","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis presents as endometrial tissue growths outside the uterine cavity with its major symptoms including dysmenorrhea and infertility. Progestin preparations, such as dienogest, are the first-line therapy for endometriosis symptoms, but may cause abnormal uterine bleeding. A gonadotropin-releasing hormone (GnRH) agonist may also be used to ease symptoms, but may induce flare-ups. Relugolix is a non-peptide GnRH antagonist that does not induce flare-ups. This study aims to compare the efficacy of relugolix with that of dienogest for reducing endometriosis-associated pain, and to evaluate if relugolix, administered prior to dienogest, decreases abnormal uterine bleeding.</p><p><strong>Methods: </strong>A multicenter, open-label, active-controlled, non-inferiority randomized study will be conducted at 11 sites in Japan. A total of 100 premenopausal patients aged ≥ 18 years with endometriosis, a maximum visual analog scale (VAS) score > 30 for endometriosis-associated pain, and dysmenorrhea or pelvic pain of at least moderate severity on the Biberoglu & Behrman (B&B) scale will be randomized in a 1:1 ratio to either a relugolix group or dienogest group. Patients in the relugolix group will receive 40 mg oral relugolix once daily for 16 weeks, followed by 1 mg oral dienogest twice daily for 24 weeks. Patients in the dienogest group will receive oral dienogest 1 mg twice daily for 24 weeks. The primary outcome will be change in maximum VAS score for endometriosis-associated pain from baseline to 13-16 weeks after start of treatment. The secondary outcomes will include VAS score for dyspareunia, B&B score for dysmenorrhea, severity of induration in the pouch of Douglas, restricted uterine mobility, pelvic tenderness, quality of life, analgesic use, and ovarian endometrioma diameter. The safety outcomes will include treatment-emergent adverse events, bone density, bone markers, menstrual status, genital bleeding, and endometrial thickness.</p><p><strong>Discussion: </strong>This study will determine the efficacy of relugolix for improving endometriosis-associated pain and dienogest-induced abnormal uterine bleeding. The results will support treatment decisions regarding endometriosis-associated pain, and the introduction of new treatments to reduce dienogest-induced abnormal uterine bleeding.</p><p><strong>Trial registration: </strong>Japan Registry of Clinical Trials ID jRCTs061230064. Registered on 29 September 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"41"},"PeriodicalIF":2.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256467","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":"TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes-statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial.","authors":"Sophie Zaloumis, Matthew J Summers, Jeffrey J Presneill, Rinaldo Bellomo, Lee-Anne S Chapple, Marianne J Chapman, Adam M Deane, Suzie Ferrie, Craig French, Sally Hurford, Nima Kakho, Matthew J Maiden, Stephanie N O'Connor, Sandra L Peake, Emma J Ridley, An Tran-Duy, Patricia J Williams, Paul J Young, Amalia Karahalios","doi":"10.1186/s13063-025-08759-0","DOIUrl":"10.1186/s13063-025-08759-0","url":null,"abstract":"<p><strong>Background: </strong>The TARGET Protein trial will evaluate the effect of greater enteral protein delivery (augmented protein) on clinical outcomes of critically ill adult patients when compared to usual care.</p><p><strong>Objective: </strong>To describe the statistical analysis plan for the TARGET Protein trial.</p><p><strong>Methods: </strong>TARGET Protein is a cluster randomized, cross-sectional, double cross-over, open-label, registry-embedded, pragmatic clinical trial conducted across Australia and New Zealand. The trial randomized eight intensive care units (ICU) to receive enteral formula containing either higher dose enteral protein (augmented protein) or usual dose protein in a 1:1 ratio. Each ICU received one trial formula for a 3-month period and then switched to the alternate formulae. This sequence was repeated, for a total trial length of 12 months. The primary outcome is the number of days free of the index hospital and alive at day 90. Secondary outcomes include proportion of patients alive at day 90, survivor-only analysis of days free of the index hospital at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. The statistical methods and models which will be used to estimate the effects for the primary and secondary outcomes are described. All statistical models will account for the cluster-randomized cross-over design to ensure correct estimation of the 95% confidence intervals. Trial enrolment is complete with 3412 patients enrolled. Data linkage is ongoing.</p><p><strong>Conclusion: </strong>This statistical analysis plan enables transparent reporting of the TARGET Protein trial. It will reduce the risk of potential selective reporting biases.</p><p><strong>Trial registration: </strong>Australian New Zealand Clinical Trials Registry (ACTRN12621001484831). Registered on November 1, 2021.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"42"},"PeriodicalIF":2.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366095","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":"Protocol paper: randomized controlled trial of the smart online-to-offline model development for chronic diseases management through digital health in real world setting.","authors":"Jae Eun Shin, Juho Choi, Heejung Lee, Suk-Won Lee, Juhwan Oh","doi":"10.1186/s13063-025-08735-8","DOIUrl":"10.1186/s13063-025-08735-8","url":null,"abstract":"<p><strong>Background: </strong>Chronic diseases such as diabetes and hypertension pose significant health and economic challenges globally, and South Korea is no exception. Innovative digital health services have the potential to revolutionize chronic disease management by providing patients with real-time, personalized care and empowering them to take an active role in their health. There is a critical need to evaluate the effectiveness of such services. This protocol describes a randomized controlled trial that evaluates the effectiveness of an online-to-offline (O2O) digital healthcare service for patients with chronic diseases, specifically diabetes and hypertension, in Pyeongchang-gun.</p><p><strong>Methods: </strong>This study presents a comprehensive protocol for the assessment of an online-to-offline (O2O) digital health service model aimed at managing chronic diseases. The study consists of two main groups of participants: those with diabetes and those with hypertension. Participants are randomized into treatment and control arms for each group. The intervention includes personalized digital healthcare support, continuous data monitoring, and online education, with primary care provided by healthcare professionals. To evaluate the primary and secondary outcomes-such as HbA1c, systolic blood pressure, and cholesterol levels-the study applies a range of statistical methods. These include intention-to-treat (ITT) analysis to account for all randomized participants, regression models to estimate the treatment effect, and adjustments for baseline covariates to improve precision. Subgroup analyses will explore variations in treatment effects based on factors such as intervention intensity, comorbidity, and healthcare provider.</p><p><strong>Discussion: </strong>This protocol outlines a novel approach to evaluating the O2O digital health service model for chronic disease management. It offers insights into the nuanced effects of the intervention, highlighting the potential for tailoring future interventions for maximum benefit. By assessing its real-world effectiveness, this study can inform healthcare policies, expand the application scope of O2O service models, and identify additional chronic diseases that can benefit from digital health services. This research bridges the gap between theory and practice, contributing to evidence-based healthcare decision-making and improving patient outcomes in the era of digital health.</p><p><strong>Trial registration: </strong>This study is registered at ClinicalTrials.gov of the US National Library of Medicine. The registration number is NCT06150508, and the registered date is 2023-11-29.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"40"},"PeriodicalIF":2.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256528","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}