Trials最新文献

{"title":"Are estimands being correctly used? A review of UK research protocols.","authors":"Timothy P Clark, Richard H Wicentowski, Suzie Cro, Matthew R Sydes, Brennan C Kahan","doi":"10.1186/s13063-025-08991-8","DOIUrl":"10.1186/s13063-025-08991-8","url":null,"abstract":"<p><strong>Background: </strong>The use of estimands in clinical trials was formalised with the adoption of the final International Conference on Harmonisation E9 Addendum on Estimands and Sensitivity Analysis in Clinical Trials (ICH E9(R1) Addendum) in November 2019. The declared objective of the ICH E9(R1) Addendum is to bring clarity and transparency to the research question of interest. For this to be achieved, the estimand must be described in accordance with the requirements of the ICH E9(R1) Addendum so that the target treatment effect is clear to all stakeholders. Previous reviews of publications and published protocols have found that few trials explicitly defined the primary estimand. To obtain a more complete picture of how the use of estimands has changed over time, whether trials are using estimands correctly (i.e. correctly defining the five attributes of an estimand), and which strategies are being used to handle intercurrent events, we obtained access to an extensive database of original research protocols (n = 29,212) submitted to the United Kingdom's Health Research Authority, which oversees ethical review of clinical trials.</p><p><strong>Methods: </strong>Protocols were eligible for review if they included the term 'estimand' and attempted to define at least one attribute of the primary estimand. For eligible protocols, we extracted information on trial characteristics such as whether the trial was randomized and the therapeutic area, as well as whether the estimand attributes used for the primary outcome were correctly defined, and which strategies were used to handle intercurrent events.</p><p><strong>Results: </strong>We found that the number of protocols defining a primary estimand increased starkly with publication of the ICH E9(R1) Addendum (approximately 3 protocols/year pre-ICH E9(R1) Addendum vs. 18 protocols / year during the consultation period vs. 23 protocols in the year following the adoption of the ICH E9(R1) Addendum). However, the description of the primary estimand was suboptimal; many protocols failed to mention specific attributes (such as population or treatment conditions) in the estimand description, and many protocols incorrectly defined estimand attributes (e.g. by describing the estimand population based on their analysis population).</p><p><strong>Conclusions: </strong>Although release of the ICH E9(R1) Addendum has dramatically increased the use of estimands in clinical trials, their reporting is suboptimal. There is still work to be done to ensure estimands reach their full potential in bringing clarity and focus to research questions.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"310"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970736","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":"Efficacy of hybrid blood purification for SA-AKI subtypes identified by CCL14: study protocol for a single-centre randomized controlled clinical trial.","authors":"Keran Shi, Wei Jiang, Lin Song, Xianghui Li, Jing Wang, Renyan Zhao, Haixia Wang, Fan Sun, Ran Wang, Cenlu Pu, Chuanqing Zhang, Luanluan Li, Yunfan Feng, Jiangquan Yu, Ruiqiang Zheng","doi":"10.1186/s13063-025-09058-4","DOIUrl":"10.1186/s13063-025-09058-4","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated acute kidney injury (SA-AKI) is a commonly encountered complex heterogeneous syndrome in critically ill patients with sepsis. Under the interaction of genotype and pathogenic factors, SA-AKI can lead to various clinical phenotypes and subphenotypes, and this heterogeneity complicates the assessment of the efficacy of treatment measures for sepsis in clinical trials. Early identification of SA-AKI high-risk patients with specific subphenotypes and timely implementation of supportive treatments may improve adverse outcomes for these patients. High levels of C-C motif chemokine ligand 14 (CCL14) serve as a biomarker that can early identify critically ill patients with persistent SA-AKI. However, the effects of different supportive treatment strategies on the prognosis of SA-AKI patients identified by CCL14 remain unclear. We hypothesize that integrated blood purification (HBP) therapy has a beneficial effect in the treatment of SA-AKI identified by CCL14.</p><p><strong>Methods: </strong>This is a single-center, blinded, randomized controlled trial. After the patients were admitted to the ICU, blood and urine samples were taken, and the urine CCL14 concentration was measured. Subsequently, they were randomly assigned to the continuous veno-venous hemofiltration (CVVH) group and the hybrid blood purification (HBP) group. The HBP group received blood hemoperfusion (HP) treatment using the HA380 hemoperfusion filter (Jafron, China) and CVVH treatment using the AN69 ST100 blood filter (Baxter, USA). The CVVH group used only the AN69 ST100 blood filter (Baxter, USA) and selected the CVVH mode for continuous renal replacement therapy (CRRT). The primary outcome was the all-cause mortality rate at 30 days after enrollment. The secondary outcomes included the all-cause mortality rate at 90 days, the incidence of chronic kidney disease (CKD) within 90 days, changes in kidney function 72 h after enrollment, variations in endotoxin levels, changes in coagulation function parameters, alterations in inflammatory factor levels, changes in plasma endothelial barrier-related indicators, variations in hemodynamic parameters, changes in SOFA (Sequential (Sepsis-related) Organ Failure Assessment) score, changes in Apache II score, duration of kidney replacement therapy (KRT) during hospitalization, duration of mechanical ventilation, duration of stay in ICU, and duration of stay in hospital.</p><p><strong>Discussion: </strong>This study aims to explore the impact of the HBP therapy on the 30-day all-cause mortality rate of patients with SA-AKI subtypes recognized by CCL14, providing relatively reliable research evidence for determining the optimal treatment approach for patients with persistent severe SA-AKI in clinical practice.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (CHICTR), ChiCTR2400093572. Registered on 9 December 2024, https://www.chictr.org.cn/showproj.html?proj=241688.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"312"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970700","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 effectiveness of first-line preventive treatment of migraine in primary care: study protocol for a pragmatic clinical trial (PREMI study).","authors":"Maria Giner-Soriano, Rosa Morros, Ramon Monfà, Dan Ouchi, Silvia Fernández-García, Cristina Vedia, Sara Bonet Monné, Eva María Calvo Martínez, Silvia Copetti Fanlo, Noemí Morollón, Robert Belvís Nieto, Claudia Erika Delgado-Espinoza, Ana García-Sangenís","doi":"10.1186/s13063-025-08961-0","DOIUrl":"10.1186/s13063-025-08961-0","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a neurological disorder affecting approximately 12% of the population, more frequent in women, causing disability. Preventive treatment is recommended to prevent chronification and analgesics' abuse and to improve quality of life, but not all candidates receive it. Common preventive drugs include amitriptyline, flunarizine, propranolol, and topiramate. Their effectiveness and safety have not yet been assessed in our setting. The objective of this study is to evaluate the effectiveness of these drugs in reducing the monthly migraine days (MMD) and to evaluate their safety.</p><p><strong>Methods: </strong>Phase IV, pragmatic randomized clinical trial of four parallel groups, open and multicentric, in Primary Care in Catalonia, Spain. We will include adults with migraine eligible for preventive treatment. They will be randomized to the following: (1) propranolol, (2) amitriptyline, (3) flunarizine, or (4) topiramate. The main efficacy measure will be the change in the mean MMD at week 12 in comparison to the mean MMD at baseline. Other secondary efficacy and safety measures will be assessed. The main non-inferiority analysis will be conducted in the per protocol population at week 12, comparing topiramate versus propranolol as the main analysis, and amitriptyline and flunarizine versus propranolol as exploratory analyses.</p><p><strong>Discussion: </strong>There are epidemiological, clinical and pharmacological sex-differences in migraine which may result in differences in the use of migraine preventive drugs. However, the effectiveness of the most frequent preventive treatment and the differences in effectiveness and safety between women and men have not yet been studied. Moreover, as new expensive drugs have been authorized for preventive treatment, indicated when the usual drugs have failed, assessing the effectiveness and safety of the usual oral preventive drugs through a clinical trial is especially important. We also plan to evaluate their cost-effectiveness, and the clinical trial will count on an active contribution from patients through an app designed for this purpose, which may help in the management of the disease in the future.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID: NCT06499116 ( https://clinicaltrials.gov/study/NCT06499116 ). Trial registration date: July 12, 2024. EU CT Number: 2024-513597-22. Protocol ID: IJG-PREMI-2024.</p><p><strong>Sponsor: </strong>Fundació d'Investigació en Atenció Primària Jordi Gol i Gurina. Gran Via de les Corts Catalanes 587, àtic. 08007, Barcelona, Spain.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"311"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970412","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":"Minimal endoscopic sphincterotomy with papillary balloon dilation versus endoscopic sphincterotomy for the treatment of common bile duct stones (MARBLE Trial): study protocol for a multicenter randomized controlled trial.","authors":"Tadahisa Inoue, Akinori Maruta, Junichi Kaneko, Toji Murabayashi, Hirofumi Okuda, Masato Yano, Rena Kitano, Shinya Uemura, Shota Iwata, Shun Futagami, Takuya Koizumi, Tomoya Kitada, Yosuke Ohashi, Yosuke Kobayashi","doi":"10.1186/s13063-025-09076-2","DOIUrl":"10.1186/s13063-025-09076-2","url":null,"abstract":"<p><strong>Background: </strong>The first-line treatment for common bile duct stones (CBDS) is endoscopic transpapillary stone removal, typically performed using either endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD). However, EST is associated with risks of bleeding and perforation, while EPBD carries a significant risk of post-procedural pancreatitis. Recently, a combined approach involving minimal EST followed by EPBD (ESBD) has been reported to mitigate these drawbacks, offering potentially safer and more effective outcomes. Nevertheless, no prospective study has adequately evaluated the utility of ESBD, as prior studies were mainly observational or limited by small sample sizes. Therefore, we designed a randomized controlled trial to investigate whether ESBD is superior to EST for the treatment of small CBDS.</p><p><strong>Methods: </strong>This study is a multicenter, randomized, open-label, parallel-group trial; outcome assessors will not be blinded, but objective predefined criteria will be used to minimize bias. Eligible participants will include patients aged 18 years or older diagnosed with CBDS who require endoscopic stone removal, with eligibility confirmed via imaging modalities. After confirming eligibility, patients will be randomly assigned in a 1:1 ratio to either the ESBD group or the EST group. In the ESBD group, a minimal sphincterotomy will first be performed, followed by balloon dilation for stone extraction. In the EST group, a medium incision extending beyond the hooding fold will be performed prior to stone extraction. The primary endpoint is the incidence of procedure-related adverse events, including pancreatitis, bleeding, and perforation. Secondary endpoints include technical success rate, clinical success rate, procedure time, need for lithotripsy, and stone recurrence rate.</p><p><strong>Discussion: </strong>This study is the first multicenter, randomized controlled trial to prospectively evaluate the efficacy and safety of ESBD for the treatment of small CBDS. The findings are expected to determine whether ESBD can serve as a new standard therapeutic option compared with conventional EST.</p><p><strong>Trial registration: </strong>Japan Registry of Clinical Trials: jRCT1040250008. Registered on 21 April 2025. ( https://jrct.mhlw.go.jp/en-latest-detail/jRCT1040250008 ).</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"307"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970739","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 for a randomized controlled trial of a resistance exercise training to treat major depression via cerebrovascular mechanisms (RESIST Trial).","authors":"Jacob D Meyer, Seana L Smith, John M Gidley, Abigail Molina, Sydney L Churchill, Shania J E Kelly, Jeni E Lansing, Nathaniel G Wade, Alison L Phillips, Peng Liu, Matthew P Herring, Thomas A Murray, Jill N Barnes, Simon B Goldberg, Wesley K Lefferts","doi":"10.1186/s13063-025-09025-z","DOIUrl":"10.1186/s13063-025-09025-z","url":null,"abstract":"<p><strong>Background: </strong>Many adults with major depressive disorder (MDD) do not engage in treatment and may also not respond when current frontline treatments are completed. Resistance exercise training (RET) is an understudied behavioral treatment option, which may help with MDD management through improving cerebral blood flow that is commonly impaired in adults with MDD. The purpose of this study is to use gold-standard research methods to determine the validity (clinical efficacy) of RET for treating MDD and to determine potential cerebrovascular pathways through which RET might improve MDD symptoms.</p><p><strong>Methods: </strong>This study will be a randomized controlled trial of 200 adults with DSM-5-diagnosed MDD of at least mild severity. Participants will be randomized to 16 weeks of twice-weekly RET at either guidelines-based high dose (60% one-repetition maximum initial load; n = 100) or a low-dose/SHAM (30% one-repetition maximum initial load; n = 100) progressive, upper- and lower-body program using resistance machines. The primary clinical outcomes of this trial are depressive symptom severity, assessed via clinician-rated GRID-Hamilton Depression Rating Scale and self-reported Quick Inventory of Depressive Symptomatology. Secondary outcomes that will examine potential mediators are cerebral blood flow (via cerebral blood velocity and pulsatility) and self-efficacy (via New General Self-Efficacy Scale and RET Task Self-Efficacy). Group differences will be evaluated during assessment visits at weeks 0 (Baseline), 8, 16 (Post-Intervention), 26, and 52. Additional analyses will explore predictors of treatment success and participants' maintenance of the RET past the active intervention.</p><p><strong>Discussion: </strong>RET is an understudied behavioral treatment for MDD. This randomized controlled trial will critically build on previous studies by using a large sample size, rigorously examining potential (provocative, plausible) biological and psychological mechanisms of RET's hypothesized antidepressant effects, and determining potential persistent effects with short- and long-term follow-up assessments. If clinical efficacy is confirmed, RET would be added as a highly translatable, accessible, low-cost alternative treatment option for individuals with MDD. Further effectiveness and implementation research would be required if efficacy is confirmed in this trial.</p><p><strong>Trial registration: </strong>This trial is registered on ClinicaTrials.gov (ID: NCT06110897; October 20th, 2023; https://clinicaltrials.gov/study/NCT06110897 ).</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"306"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970722","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 effects of remimazolam on the incidence of severe hypoxemia during sedated hysteroscopy for assisted reproduction in overweight or obese patients: a randomized controlled clinical trial.","authors":"Yanhua He, Jie Zhou, Xibing Ding, Xiaorong Huai, Shujing Lin, Weifeng Yu, Diansan Su","doi":"10.1186/s13063-025-09054-8","DOIUrl":"10.1186/s13063-025-09054-8","url":null,"abstract":"<p><strong>Background: </strong>Hypoxemia is the most common adverse reaction during sedated hysteroscopy. Obesity is a risk factor for hypoxemia. For hysteroscopy, propofol is the most commonly used sedative. However, it can cause dose-dependent respiratory depression. This drawback has driven the search for sedatives with less respiratory depressant effects. Remimazolam is a new benzodiazepine drug with several advantages, including minimal impact on the respiratory and circulatory systems. This study aims to compare remimazolam and propofol in terms of safety and efficacy in patients with overweight or obesity who are undergoing sedated hysteroscopy.</p><p><strong>Methods: </strong>This prospective, single-center, randomized, single-blind, controlled clinical trial will be conducted to examine the effect of remimazolam on the incidence of severe hypoxemia in patients with overweight or obesity. Patients (n = 600) scheduled to undergo sedated hysteroscopy will be randomly assigned to either the control or experimental group and will be sedated using propofol or remimazolam, respectively.</p><p><strong>Discussion: </strong>The main objective of this study is to determine whether remimazolam can reduce the incidence of severe hypoxemia in patients with overweight or obesity during hysteroscopy. The results of this study are expected to provide evidence on the safety and efficacy of remimazolam in patients with overweight or obesity, which will enhance patient comfort and safety during sedated hysteroscopy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT06187896. Registered on January 3, 2024.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"309"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970595","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":"Mini-laparotomy versus transrectal natural orifice specimen extraction for minimally invasive colorectal cancer surgery: study protocol for a randomized controlled trial (MINITR-NOSE trial, TCAR2514 protocol).","authors":"Ai-Lun Lo, Yu-Jen Hsu, Yih-Jong Chern, Ching-Chung Cheng, Bor-Kang Jong, Zhen-Hao Yu, Li-Yang Chan, Jeng-Fu You","doi":"10.1186/s13063-025-09039-7","DOIUrl":"10.1186/s13063-025-09039-7","url":null,"abstract":"<p><strong>Background: </strong>Minimally invasive surgery (MIS) has improved colorectal cancer (CRC) treatment by reducing recovery time, pain, and infection risk compared to traditional open surgery, though a mini laparotomy is still needed for specimen removal. Natural orifice specimen extraction (NOSE) offers a promising alternative by using natural body openings for extraction, potentially minimizing complications further, yet requires more evidence to confirm its safety and effectiveness over conventional methods.</p><p><strong>Methods: </strong>This single-center randomized controlled trial at Linkou Chang-Gung Memorial Hospital includes CRC patients meeting specific eligibility criteria, randomly assigned to undergo either NOSE or conventional MIS. Primary outcomes focus on postoperative C-reactive protein (CRP) levels as a marker of inflammation, with secondary outcomes evaluating short-term complications, recovery, readmission, and long-term survival. Both groups will receive routine perioperative care following modified Enhanced Recovery After Surgery (ERAS) protocols, with postoperative pain and complications systematically recorded and graded.</p><p><strong>Discussion: </strong>This study seeks to determine whether the NOSE approach offers advantages over conventional MIS by reducing inflammation and complications, potentially improving patient recovery and outcomes. If effective, NOSE may present a less invasive alternative for CRC resection, contributing to advancements in colorectal surgical oncology.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05740267. Registered on March 1, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"304"},"PeriodicalIF":2.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970662","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 DEXA-PSYCH Study-dexamethasone for moderate-to-severe depression: study protocol for a double-blind, randomized, parallel-group, placebo-controlled trial.","authors":"Troels Boldt Rømer, Camilla Gøtzsche Frederiksen, Pernille Bølling Hansen, Rune Haubo Bojesen Christensen, Michael Eriksen Benros","doi":"10.1186/s13063-025-08989-2","DOIUrl":"10.1186/s13063-025-08989-2","url":null,"abstract":"<p><strong>Background: </strong>Globally, depression represents one of the leading causes of years lived with disability. The effects of current pharmacological treatments are small-to-moderate and often delayed by weeks. Immunological disturbances have been associated with depression and meta-analyses have suggested that anti-inflammatory agents have moderate-to-large anti-depressant effects. The largest effects were reported for glucocorticoids. However, previous trials were too small to legitimize standard use of glucocorticoids as add-on treatment in depression. The purpose of the DEXA-PSYCH study is to investigate the effect and safety of short-term, oral dexamethasone compared to placebo as add-on therapy in moderate-to-severe depression.</p><p><strong>Methods: </strong>The DEXA-PSYCH trial is an investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group superiority trial. Three-hundred participants meeting criteria for moderate-to-severe depression will be randomized in a 1:1 ratio to 1 week of either dexamethasone (4 mg/day for 4 days, subsequently 2 mg/day for 3 days) or placebo as add-on treatment to treatment as usual. Both in- and out-patients are eligible. Exclusion criteria include, but are not limited to, psychotic disorders, bipolar disorder, and diabetes. The primary outcome is change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score on day 7 and will be analyzed through a Mixed Model for Repeated Measurements (MMRM) in an intention-to-treat analysis. Key secondary outcomes include response and remission rates, efficacy 3 weeks after the intervention, effects on quality of life, and safety outcomes. Other secondary outcomes include overall functioning, fatigue, anxiety, labor-market affiliation, and associations between inflammatory biomarkers and treatment response.</p><p><strong>Discussion: </strong>The DEXA-PSYCH trial represents the largest trial of its kind globally. If the trial confirms findings from previous, smaller studies, short-term oral dexamethasone could become an attractive augmentation strategy if acute anti-depressant effects are warranted. Dexamethasone is an off-patent, well-known drug readily repurposed for new indications.</p><p><strong>Trial registration: </strong>EU Clinical Trials Number 2022-501428-45-00, Registered 25th of July 2022 in the EU Clinical Trials Information System ( https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2022-501428-45-00 ). WHO Universal Trial Identifier U1111-1280-7614.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"303"},"PeriodicalIF":2.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970401","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":"Mate Whenua-follow-up after early medical abortion: study protocol for a randomized controlled trial.","authors":"Michelle R Wise, E Jane MacDonald, Alison Knowles, Sally Talbot, Stephanie Shankar, Brittany Gibbons, Bev Lawton, Varsha Parag, Ashleigh O'Mara Baker, Sophia Amjad","doi":"10.1186/s13063-025-09016-0","DOIUrl":"https://doi.org/10.1186/s13063-025-09016-0","url":null,"abstract":"<p><strong>Background: </strong>Early medical abortion (EMA) is safe and effective; an uncommon but crucial adverse outcome is ongoing live pregnancy. The best method of follow-up after EMA to detect ongoing pregnancy is a critical research gap. Few trials compare blood or urine pregnancy tests to ultrasound scans, and no trial compares these tests to each other. The aim is to evaluate the completeness of follow-up of two methods of follow-up after EMA- self-assessment with low-sensitivity urine pregnancy test result or serial serum βhCG blood tests. Secondary aims will evaluate whether self-assessment follow-up is safe and acceptable to patients and clinicians.</p><p><strong>Methods: </strong>This is a multicentre randomised controlled trial in New Zealand. Eligible women and pregnant people having EMA will be randomised to self-assessment or blood test follow-up. The primary outcome is 'lost to follow-up.' To detect a decrease in 'lost to follow-up' rate from baseline of 15% to 7.5%, with 90% power and a two-sided type 1 error of 0.05, the sample size required is 736 participants, in a 1:1 ratio.</p><p><strong>Discussion: </strong>If self-assessment reduces lost to follow-up, has additional clinical benefits, and is safe, cost-effective, and acceptable to women and clinicians, we anticipate change in EMA follow-up practice around the world. We think self-assessment will be welcomed as part of a patient-centred package of care following EMA.</p><p><strong>Trial registration: </strong>This trial was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR) on 21 August 2023, registration number ACTRN12623000890639; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384373.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"305"},"PeriodicalIF":2.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970672","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":"Implementation of Metformin Therapy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): study protocol for a phase III, multi-centre, randomized, placebo-controlled trial evaluating the long-term efficacy of metformin in slowing the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease.","authors":"Kitty St Pierre, Ragada El-Damanawi, David W Johnson, Carmel M Hawley, Andrea K Viecelli, Vivekanand Jha, Suetonia C Green, Loreto Gesualdo, Charani Kiriwandeniya, Pushparaj Velayudham, Liza A Vergara, Gabor Mihala, Misa Matsuyama, Peta-Ann Paul Brent, Andrew J Mallett","doi":"10.1186/s13063-025-09010-6","DOIUrl":"10.1186/s13063-025-09010-6","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common reason for commencement of dialysis globally. There is an urgent need for treatments to slow the loss of kidney function and prevent complications in people with ADPKD. A growing body of evidence suggests metformin may have a therapeutic role in slowing cyst progression in ADPKD.</p><p><strong>Methods: </strong>IMPEDE-PKD is a prospective, multicentre, international, double-blind, randomized controlled trial of metformin versus placebo in adults with ADPKD. From November 2022, a total of 1174 participants will be targeted for recruitment globally, from participating kidney units in Australia, the UK, New Zealand, India, Hong Kong, South-East Asia and Europe. Following a 10-week run-in phase of extended-release metformin up-titrated to a maximum dose of 2000 mg, participants will be randomized 1:1 to receive either metformin or placebo and followed for 2 years. The primary outcome will be the rate of kidney function decline measured as a change in the estimated glomerular filtration rate. Secondary outcomes include other clinical markers for ADPKD progression (albuminuria, development of kidney failure), mortality, health-related QOL, pain, medication side effects, tolerability and cost-effectiveness.</p><p><strong>Discussion: </strong>If proven effective, metformin would positively impact the well-being of people with ADPKD as a treatment option that is widely available and affordable.</p><p><strong>Trial registration: </strong>CLINICALTRIALS: gov NCT04939935. Registered on 25 June 2021.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"302"},"PeriodicalIF":2.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970670","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}