Trials最新文献

{"title":"The FROSTBLOCK trial: Protocol for a randomized controlled trial of intra-articular corticosteroid injection with or without suprascapular nerve block in frozen shoulder.","authors":"Marc Schiltz, Jonas Croes, Lina van Brabander, Stijn Roggeman, Lisa Goudman, Maarten Moens, Jo Nijs, Nicole Pouliart, Bénédicte Forthomme, Samar M Hatem","doi":"10.1186/s13063-025-09123-y","DOIUrl":"10.1186/s13063-025-09123-y","url":null,"abstract":"<p><strong>Background: </strong>Frozen shoulder is a challenging musculoskeletal disorder, affecting between 2 and 5% of people, with a higher incidence among those with diabetes and thyroid issues. This condition can persist for years and can be very demanding for both patients and healthcare providers due to the intense pain and restricted shoulder movement. Literature shows that intra-articular corticoid injection (IACI) and suprascapular nerve block (SSNB) can improve pain and range of motion in these patients. The objective of this study is to investigate if there is any significant difference in pain reduction and functional recovery when treated with a combination of gleno-humeral IACI and SSNB compared to a gleno-humeral IACI paired with a placebo SSNB.</p><p><strong>Methods: </strong>A two-arm, single-centre, randomized, parallel-group controlled trial will be conducted. Eligible patients will be randomly assigned (1:1 allocation) to long-acting SSNB + IACI and placebo SSNB + IACI. The primary endpoint is the mean change from baseline to 3 months in the Shoulder Pain and Disability Index (SPADI) score. Secondary outcomes will evaluate quality of life, functionality, pain (measured by a Numeric Pain Rating Scale), kinesiophobia, work status, health care service, and a safety assessment. The main paper will be based on the repeated measures collected up to 12 months from baseline.</p><p><strong>Discussion: </strong>The aim of this study is to determine the additional effect on pain relief and functional improvement in frozen shoulder patients when a long-acting SSNB is administered, compared to a placebo SSNB, in combination with an intra-articular corticosteroid injection. Additionally, we will aim to determine which patients benefit most from these treatments. This study could lead to a change in the standard of care for patients in the painful phase of frozen shoulder.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT06229964. Registered on 9 January 2024.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"383"},"PeriodicalIF":2.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193107","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":"Real-time 3D confirmation of complete ablation with margins as a local cure for colorectal liver metastases: the ACCLAIM trial.","authors":"Constantinos T Sofocleous, Matthew R Callstrom, Elena N Petre, Mithat Gonen, William S Rilling, Muneeb Ahmed, Alexis Kelekis, Michael C Soulen, Philippe Pereira, Laura Crocetti, Damian E Dupuy, Luigi Solbiati","doi":"10.1186/s13063-025-09006-2","DOIUrl":"10.1186/s13063-025-09006-2","url":null,"abstract":"<p><strong>Background: </strong>Treatment failure and local tumor progression (LTP) after thermal ablation (TA) have been attributed to insufficient minimal margin (MM) ablation zone coverage of the target tumor.</p><p><strong>Methods: </strong>This prospective, open-label, multicenter, international trial will enroll approximately 275 patients with one to three colorectal liver metastases (CLM) (for a total of 330 tumors) each up to 2.5 cm in largest diameter, eligible for local cure using microwave ablation (MWA). Any FDA cleared or CE-marked MWA device can be used. MWA will be performed with the intent to create a MM of at least 5 mm and ideally ≥ 10 mm. MM size will be documented intraprocedurally with contrast-enhanced computed tomography (CECT) immediately post-MWA and again within 4-8 weeks after MWA using any FDA cleared or CE-marked image-processing software to provide a 3D assessment of the ablation zone (AZ) and MM. An independent assessment of the MM by a central physician reviewer with expertise on AZ assessments will be conducted within 7 days of the MWA with 3D image-processing confirmation software and again within 7 days after the 4-8 weeks post-MWA CECT. A MM of 5.0 mm will represent the necessary condition for technical success of MWA. For MMs under 5 mm, repeat MWA will be performed within the same session whenever feasible/safe, and/or within 30 days from detection of the insufficient MM to create a sufficient MM (> 5 mm). MM size will be correlated with time to local tumor progression (TTLP). Local progression-free (LPFS) and hepatic disease-free survival (accounting for all tumors ablated) stratified by MM of 5.0-9.9 mm and ≥ 10.0 mm will be assessed with Kaplan-Meier and competing risk methodologies.</p><p><strong>Discussion: </strong>This study aims to demonstrate that MWA of CLM ≤ 2.5 cm with 3D image-processing confirmation software of MM over 5 mm achieves definitive local tumor control. This will help establish margin confirmation as a new standard of care for MWA of CLM.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05265169. Registered on January 13, 2023.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"360"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179003","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":"Validation of a long-term and effective physical exercise management for ankylosing spondylitis: study protocol for a decentralized randomized controlled trial.","authors":"Lei Huang, Yinghua Pan, Xiaoyun Tang, Hexiao Ding, Qiaorui Wang, Qiwen Ma, Huifen Liu, Hengying Fang","doi":"10.1186/s13063-025-09096-y","DOIUrl":"10.1186/s13063-025-09096-y","url":null,"abstract":"<p><strong>Background: </strong>Ankylosing spondylitis (AS), a chronic inflammatory disease, leads to significant physical and psychosocial burdens due to progressive spinal rigidity and high disability rates. Although exercise is well-established as a key factor in delaying deformity and enhancing function, maintaining long-term adherence poses a significant hurdle. This study aims to validate the effectiveness of an Exercise Management Mode based on the Attitude-Social Influence-Self-Efficacy (ASE) model (EMM-ASE) in enhancing exercise behavior and clinical outcomes among AS patients.</p><p><strong>Methods: </strong>This decentralized randomized controlled trial (D-RCT) will enroll 120 AS patients from the Guangdong Rheumatology and Immunology Specialty Alliance. Participants will be randomized 1:1 into an intervention group (EMM-ASE) or a control group (routine management). The intervention group receives personalized, stage-based exercise strategies via the AS Exercise Mobile Intelligent Management Platform, including real-time feedback, social support, and biweekly network-broadcasted exercise sessions. The control group receives standard exercise guidance and access to patient support groups. Primary outcomes are exercise level (measured by the International Physical Activity Questionnaire, IPAQ). Secondary outcomes include functional capacity (Bath Ankylosing Spondylitis Functional Index, BASFI), disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI), fatigue severity (Fatigue Severity Scale, FSS), quality of life (Ankylosing Spondylitis Quality of Life, ASQoL), and exercise adherence. Data will be collected at baseline, 1, 3, and 6 months. Statistical analyses include intention-to-treat analysis using mixed linear models, trajectory analysis via latent class models, and sensitivity analyses.</p><p><strong>Discussion: </strong>The intervention group in this D-RCT, which innovatively applies a mobile platform to AS exercise management, is expected to show more significant improvements in primary and secondary outcomes than the control group. Specifically, at follow-up points, it is anticipated that they will have higher IPAQ scores, lower BASFI scores, and better performance in other indicators. This design would prove the superiority of the EMM-ASE strategy, offering a new effective model for AS treatment.</p><p><strong>Trial registration: </strong>The study protocol was registered with Chinese Clinical Trial Registry on 12 May 2025, https://www.chictr.org.cn/showproj.html?proj=272057 (registration number: ChiCTR2500102260).</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"361"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179128","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":"Effect of dexmedetomidine on perioperative blood glucose regulation in type 2 diabetic patients undergoing laparoscopic colorectal cancer radical resection: a randomised double-blinded controlled trial.","authors":"Wei Dai, Jinlong Zhou, Lunjing Qu, Kaihua He","doi":"10.1186/s13063-025-09094-0","DOIUrl":"10.1186/s13063-025-09094-0","url":null,"abstract":"<p><strong>Background: </strong>The stability of blood glucose levels in diabetic patients is more susceptible to fluctuations than in nondiabetic individuals. The effect of dexmedetomidine on glucose fluctuations in diabetic patients remains unclear. This study aimed to investigate the effect of intraoperative dexmedetomidine on glucose homeostasis in patients with type 2 diabetes undergoing laparoscopic colorectal cancer radical resection.</p><p><strong>Methods: </strong>80 participants with T2DM preparing for laparoscopic colorectal cancer radical resection were randomly divided into four groups: control group (group C), dexmedetomidine 1 μg ⋅ kg^-1 + 0.25 μg ⋅ kg^-1 ⋅ h^-1 (group D1), 1 μg ⋅ kg^-1 + 0.5 μg ⋅ kg^-1 ⋅ h^-1 (group D2), and 1 μg ⋅ kg^-1 + 0.75 μg ⋅ kg^-1 ⋅ h^-1 (group D3). Levels of blood glucose were measured before the intravenous infusion of dexmedetomidine (T1), 15 min after the intubation(T2), 1 h after the beginning of the surgery (T3), at the end of the surgery (T4), and 30 min after the extubation in PACU (T5).</p><p><strong>Results: </strong>Compared with the baseline levels, the levels of blood glucose from T2 to T5 in group C increased gradually but were not significantly different at each time point (p > 0.05), and there was a statistically significant rise in blood glucose in group D1 at T3, T4, and T5 and in groups D2 and D3 at T2, T3, and T4 (p < 0.05). Compared with group C, blood glucose in groups D2 and D3 was significantly higher at T3, andT4 (p < 0.05). Compared with group C, the rangeability from T1 to T3 and T1 to T4 was significantly higher in groups D2 and D3 (p < 0.05).</p><p><strong>Conclusion: </strong>Dexmedetomidine loading dose 1 μg/kg and a Maintenance dose 0.25 μg/kg/h can be used in type 2 diabetic patients for better glucose regulation without increasing the incidence of perioperative hyperglycemia, adverse effects, and extending extubation time.</p><p><strong>Trial registration: </strong>ChiCTR2100042050. Registered on January 13, 2021, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=120133 .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"362"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179065","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":"Effect of atorvastatin versus no Statin Treatment on major clinical events in Acute CardioEmbolic stroke patients without a definite indication for statin therapy: protocol for the STACE trial.","authors":"Hong-Kyun Park, Jun Yup Kim, Keun-Sik Hong, Yong-Jin Cho, Jong-Moo Park, Dongwhane Lee, Kyusik Kang, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Moon-Ku Han, Beom Joon Kim, Jihoon Kang, Tai Hwan Park, Sang-Soon Park, Jin Kyo Choi, Kyungbok Lee, Jeong-Yoon Lee, Jun Lee, Doo Hyuk Kwon, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Minwoo Lee, Man-Seok Park, Joon-Tae Kim, Kang-Ho Choi, Hyunsoo Kim, Dong-Eog Kim, Dong-Seok Gwak, Jay Chol Choi, Joong-Goo Kim, Chul-Hoo Kang, Jee-Hyun Kwon, Wook-Joo Kim, Dong-Ick Shin, Kyu Sun Yum, Sung Il Sohn, Jeong-Ho Hong, Hyungjong Park, Chulho Kim, Sang-Hwa Lee, Kwang-Yeol Park, Hae-Bong Jeong, Chan-Young Park, Kyungmi Oh, Chi Kyung Kim, Jung Hoon Han, Keon-Joo Lee, Sung Hyuk Heo, Ho Geol Woo, Juneyoung Lee, Hee-Joon Bae","doi":"10.1186/s13063-025-09097-x","DOIUrl":"10.1186/s13063-025-09097-x","url":null,"abstract":"<p><strong>Background: </strong>Evidence supporting the use of statin therapy to reduce stroke recurrence and cardiovascular events in acute cardioembolic stroke (CES) patients without atherosclerosis is limited. Past observational studies have been hampered by selection bias and unmeasured confounding factors. This study aims to investigate the potential benefits of statin therapy in acute CES patients without established indications through a registry-based, randomized clinical trial.</p><p><strong>Methods: </strong>This is a registry-based, multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) study designed to evaluate the efficacy and safety of statin therapy in acute CES patients without established indications for statin use. Patients will be randomly assigned (1:1) to either statin users or non-users, with statin users receiving atorvastatin at a dose of 10 mg or higher throughout the study period. We plan to recruit 1036 participants to detect a relative risk reduction of 43% with 80% power and a two-sided alpha error of 0.05, accounting for a 10% loss to follow-up. The primary outcome is the occurrence of a major clinical event, defined as a composite of stroke recurrence, myocardial infarction, and all-cause mortality within 3 months after the index stroke. The secondary efficacy outcomes include (1) stroke recurrence, (2) all-cause mortality, (3) vascular death, and (4) major vascular events.</p><p><strong>Discussion: </strong>This study will assist stroke physicians in determining the appropriate use of statin therapy for acute CES patients who do not have guideline-based indications.</p><p><strong>Trial registration: </strong>CRIS Registration Number: KCT0006806. Registered on November 29, 2021. URL: https://cris.nih.go.kr/cris.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"358"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178977","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":"Developing a surgical trial intervention protocol: using qualitative methods in the operating theatre.","authors":"Maureen Twiddy, Richard Jackson, Kathryn Gordon, Julie Croft, Neil Corrigan, Deborah Stocken, Saba P Balasubramanian","doi":"10.1186/s13063-025-09088-y","DOIUrl":"10.1186/s13063-025-09088-y","url":null,"abstract":"<p><strong>Introduction: </strong>Surgery is a complex intervention, so it is important to establish standards for both the standard and 'novel' procedures in randomized controlled trials (RCTs) that demonstrate that interventions are delivered as intended to fully understand and explain trial results. This study set out to identify and agree the key steps of a surgical intervention to be tested in the 'near infrared fluorescent imaging in thyroid surgery' (NIFTy) RCT to inform development of the surgical protocol, and trial materials.</p><p><strong>Method: </strong>Qualitative case studies of surgeries were undertaken prior to undertaking an RCT to evaluate the potential of a device to reduce post-surgical hypoparathyroidism. Each case study involved non-participant observation, video capture of total and completion thyroidectomies, and interviews with surgeons. A typology of operative steps was constructed. Two surveys were undertaken (1) to identify current practice around parathyroid identification; and (2) to determine surgeon views on the surgical steps. An international expert panel of six clinicians met to review findings and agree on the surgical steps (mandatory/optional) for operations in the RCT, including timing for use of fluorescence and the data items to be collected.</p><p><strong>Results: </strong>Ten case studies were undertaken. Video, observation and interview data found differences in surgical approach were driven only by pathology. A typology detailing the surgical steps and points where imaging could be used was developed. Sixty-four surgeons responded to survey 1; three-quarters always looked for parathyroid glands when operating. Forty surgeons responded to survey 2; capsular dissection of the thyroid lobe, preservation of parathyroid pedicle, and clinical assessment were important for parathyroid preservation. The expert panel agreed the key surgical components. These informed key data collection in NIFTy. Two specific surgical steps were strongly recommended and three mandated.</p><p><strong>Conclusion: </strong>Qualitative research in the operating theatre, prior to RCT allowed the identification of key components of the surgical intervention. The surveys and expert panel provided certainty about the acceptability of the surgical protocol and identified the core data to collect to evidence surgical decision making prior to embarking on the RCT. This qualitative process achieved clinical buy-in, improved trial conduct and allowed full explanation of the subsequent trial results.</p><p><strong>Trial registration: </strong>ISRCTN59074092. Registration date: 07/03/2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"368"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179006","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 olfactory enrichment on perioperative neurocognitive disorders in elderly patients undergoing orthopedic surgery: a study protocol of a multi-center randomized controlled trial.","authors":"Xinchun Mei, Jiayi Wang, Zihan Ni, Yanyan Wang, Binglei Zhao, Daniel I Sessler, Zhongcong Xie, Yuan Shen","doi":"10.1186/s13063-025-09109-w","DOIUrl":"10.1186/s13063-025-09109-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Neurocognitive disorders are prevalent among older surgical patients, yet their underlying mechanisms and effective interventions remain largely unknown. Studies in rodents and patients suggest a connection between olfactory impairment and perioperative neurocognitive disorder (PND). Previous work in mice demonstrates that anesthesia and surgery can lead to both olfactory impairment and cognitive deficits. Olfactory enrichment, which is also referred to as olfactory training (i.e., daily exposure to multiple odorants), may prove helpful. For example, olfactory enrichment appears to reduce PND-like behaviors in mice, possibly by mitigating anesthesia- and surgery-induced reductions in olfactory receptor neurons. Additionally, olfactory enrichment increases the volume and size of olfactory-related brain regions, such as the olfactory bulb and hippocampus, as well as changes in functional connectivity in non-surgical adults. Despite promising findings in mice, it remains unknown whether olfactory training reduces PND in surgical patients. We therefore propose a randomized clinical trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and analysis: &lt;/strong&gt;This sham-controlled assessor-blind randomized controlled trial will enroll 686 patients aged 65 and older who are scheduled for orthopedic Surgery expected to last at least 2h under general anesthesia. Participants will be randomized 1:1 to olfactory enrichment or sham treatment. Those assigned to the olfactory enrichment group will receive twice-daily 30-min sessions involving four distinct odors, beginning on 1 day before surgery and continuing for three postoperative days during hospitalization. Patients assigned to sham treatment will follow the same schedule, but with odorless substances in the scent dispenser. The primary outcome is the incidence of postoperative delirium, assessed using the 3-min diagnostic interview for CAM-defined delirium (3D-CAM) on postoperative days 1, 2, and 3. Secondary outcomes include the incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder, evaluated through cognitive function assessments using neuropsychological tests at baseline, 21 days, and 6 months after the anesthesia/surgery. Exploratory outcomes include the severity of delirium measured by the CAM-severity (CAM-S) tools, the severity of delayed neurocognitive recovery and postoperative neurocognitive disorder assessed through neuropsychological tests, evaluations of activities of daily living, plasma Tau-PT217 levels, and olfactory function.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This is the first clinical trial to evaluate the efficacy of olfactory enrichment in geriatric patients undergoing orthopedic surgery, filling an important gap in the treatment evidence for PND.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;The trail has been registered in ClinicalTrial.gov with the Trial Registration Number of NCT06488807. Date of registration in the primary registry: June 15, ","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"363"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178984","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":"Coenrollment of critically ill patients in PROSPECT: characteristics and association with treatment efficacy and safety.","authors":"Alex Thabane, Diane Heels-Ansdell, Nicole Zytaruk, Jennie Johnstone, François Lauzier, Yaseen M Arabi, John Muscedere, France Clarke, Lori Hand, Irene Watpool, Rebecca Porteous, Gyan Sandu, Marlene Santos, Danae Tassy, John Marshall, Lauralyn McIntyre, Ian Ball, Bram Rochwerg, Tim Karachi, Ryan Zarychanski, Francois Marquis, Jan O Friedrich, Paul Lysecki, Deborah Cook","doi":"10.1186/s13063-025-09028-w","DOIUrl":"10.1186/s13063-025-09028-w","url":null,"abstract":"<p><strong>Introduction: </strong>Coenrollment is the enrollment of one participant into more than one study. While coenrollment can enhance research efficiency, it theoretically may result in treatment interactions that distort effect estimates. This study aimed to explore the sensitivity of safety and efficacy outcomes to coenrollment in an international, blinded randomized controlled trial evaluating probiotic use in critically ill patients (PROSPECT: Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial; [NCT02462590]).</p><p><strong>Methods: </strong>In this planned secondary analysis of PROSPECT, we performed Cox proportional hazards analyses to assess the sensitivity of the treatment effect of probiotics to coenrollment on the primary outcome of ventilator-associated pneumonia. Secondarily, we examined the characteristics of coenrolled patients, studies, and centers using descriptive statistics, explored factors associated with coenrollment via a multilevel logistic regression model, and conducted Fisher's exact tests to evaluate the difference in adverse event rates (defined as Lactobacillus species from a sterile site or cultured as the sole or predominant organism from a nonsterile site) by coenrollment status.</p><p><strong>Results: </strong>Of 2650 PROSPECT participants recruited across 44 centers, 568 patients (21.4%) were coenrolled a total of 680 times across 115 studies. Coenrollment did not modify the effect of probiotics on the primary outcome of ventilator-associated pneumonia (p = 0.630). Patients who were coenrolled in any other study had a higher rate of adverse events compared to non-coenrolled patients (p = 0.011); however, post hoc testing found no difference in adverse events between patients coenrolled specifically into at least one other randomized controlled trial and patients who were not coenrolled into another randomized controlled trial (i.e., coenrolled into an observational study or not coenrolled at all; p = 0.126). Multivariable analyses found more severely ill patients (p = 0.038) and patients from centers with a longer PROSPECT recruitment period (p = 0.047) were more likely to be coenrolled.</p><p><strong>Conclusion: </strong>In this international, blinded trial, one-fifth of patients enrolled were coenrolled in at least one other study, which had no influence on the effect of probiotics on the primary outcome. Coenrolled patients were more likely to have higher disease severity, and to be recruited from a center with a longer history of participation in PROSPECT.</p><p><strong>Trial registration: </strong>The PROSPECT trial was registered in ClinicalTrials.gov NCT02462590. Registered on June 2015.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"370"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178983","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":"Use of routinely collected health data (England) to identify subsequent disease-related events in patients with primary breast cancer: a practical alternative to hospital-based follow-up for breast cancer clinical trials.","authors":"Lucy S Kilburn, Victoria Hinder, Sikhuphukile G Mahati, Judith M Bliss","doi":"10.1186/s13063-025-09085-1","DOIUrl":"10.1186/s13063-025-09085-1","url":null,"abstract":"<p><strong>Background: </strong>With continued improvements in breast cancer (BC) outcomes and risk of recurrence occurring until at least 20 years post-diagnosis, it is important to continue to follow up clinical trial participants to characterise long-term treatment impact. Traditionally, follow-up has been via hospitals, entailing burden on patients and site staff. Using routinely collected health datasets (RCHD) as an alternative method is attractive, but historically, cancer recurrence is poorly recorded, unlike initial cancer diagnosis. Here we use data collected prospectively from large, multi-centre BC clinical trials to develop and test a procedure to identify recurrence within RCHD.</p><p><strong>Methods: </strong>Data from four trials of early breast cancer (TACT2, POETIC, IMPORT-HIGH and FAST-Forward) where recurrence data has been collected prospectively (gold standard) was linked with RCHD (incl. cancer registry and hospital episode statistics; HES) managed by NHS England. The procedure identified episodes of clinical activity within RCHD to classify each event type (local and distant recurrence, second cancers, death) separately, then combined to derive time-to-recurrence (TTR), disease-free survival (iDFS) and overall survival (OS) outcomes. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Hazard ratios using Cox regression modelling, log-rank test p-values, and 3-year survival rates for the randomised treatments were reported separately for RCHD and trial data.</p><p><strong>Results: </strong>The final procedure used Cancer Registry diagnoses to identify initial BCs for quality control purposes and second primary cancers. Deaths were identified via death dates and cause. Distant recurrence was identified predominantly by direct indicators of metastases (e.g. ICD10 codes C77X-79X). Local recurrence was identified via relevant surgeries' OPCS4 codes. For TTR, iDFS and OS, agreement between study and RCHD events was reasonable. Specificity was good across all endpoints (range: 97.9-99.9% for three training datasets combined), as was NPV (range: 95.2-99.6%). Sensitivity and PPV were more variable, with sensitivity ranging between 72.9 and 97.2% and PPV ranging between 82.6 and 99.5%. Values were similar when considering the test dataset. Survival estimates for TTR, iDFS and OS were similar between study and RCHD data.</p><p><strong>Conclusion: </strong>It is possible, with reasonable accuracy, to identify cancer recurrences using RCHD in the place of hospital-based data collection after the point of primary analysis.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"359"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179132","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":"Why do common sense trials fail in the UK? Lessons learned from a trial which tested the effectiveness and cost-effectiveness of a community falls prevention programme (the Firefli study).","authors":"Joy Adamson, Arabella Scantlebury, Avril Drummond, Caroline Fairhurst, Sarah Cockayne","doi":"10.1186/s13063-025-09116-x","DOIUrl":"10.1186/s13063-025-09116-x","url":null,"abstract":"<p><strong>Background: </strong>The Firefli study was funded from a commissioned call to conduct a individually randomised controlled trial to assess the effectiveness and cost-effectiveness of Home Fire Safety Visits (also known as Safe and Well Visits) in their ability to reduce falls and improve quality of life in older adults living in the community. These visits are routinely carried out by fire and rescue services in England and aim to reduce risk of fire, support independent living and improve quality of life. In this paper, we reflect on our experience of attempting to deliver a definitive trial within the fire service, with the aim of informing future commissioning and methodological practice for non-National Health Service hosted trials in the UK.</p><p><strong>Lesson learned: </strong>It proved impossible to conduct the trial as planned in the current research landscape, randomising only 63 participants from a target of 1156. Whilst there were challenges associated with the COVID-19 pandemic, it was key issues pertaining to current regulatory requirements, the acquisition of data and lack of research culture and infrastructure with the fire service which were fundamental barriers to successful research delivery. Specifically, these barriers meant it was not feasible to implement the trial as designed to reflect actual service delivery. The adapted trial design had very low recruitment and resulted in differences between the target population and the trial population.</p><p><strong>Conclusions: </strong>Conducting trials outside of health is extremely challenging in the UK. We recommend an urgent review of research governance processes which are primarily designed for health-related research in the National Health Service and are not fit for purpose when conducting research within other sectors. Many of the challenges identified are not exclusive to delivering trials in the fire service and have wider implications as the scope for evidence-based practice expands outside of health.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT04717258.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"26 1","pages":"365"},"PeriodicalIF":2.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179143","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}