Trials[JOURNAL]
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200 papers
Efficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical trial.
Gao J, Yu H, Xu Z … +3 more , Xu Y, Wu Y, Liang P
Trials · 2026 Apr · PMID 41987330 · Full text
BACKGROUND: Procedural sedation in patients with end-stage renal disease (ESRD) is challenging due to impaired renal function, which affects drug metabolism and increases the risk of adverse events. Remimazolam, a novel...
BACKGROUND: Procedural sedation in patients with end-stage renal disease (ESRD) is challenging due to impaired renal function, which affects drug metabolism and increases the risk of adverse events. Remimazolam, a novel ultrashort-acting intravenous sedative, offers rapid onset and clearance independent of renal function, making it a potential alternative to dexmedetomidine for sedation in this patient population. This study aims to compare the efficacy and safety of remimazolam versus dexmedetomidine in ESRD patients undergoing procedural sedation. The primary hypothesis is that remimazolam will demonstrate superior sedation efficacy and a better safety profile, with reduced hemodynamic instability and faster recovery. METHODS: This is a single-center, prospective, observer-blinded, randomized controlled trial (RCT). A total of 80 ESRD patients aged ≥ 18 years scheduled for peritoneal dialysis catheter placement or removal will be randomly assigned to receive either remimazolam or dexmedetomidine. The primary outcome is the sedation success rate, defined as achieving a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤ 1 within 10 min of drug administration. Secondary outcomes include time to sedation, intraoperative movements, the duration of BIS values < 60 or > 80 during anesthesia maintenance, recovery time, the incidence of adverse events, incidence of postoperative nausea and vomiting (PONV), and postoperative pain scores. DISCUSSION: This is the first RCT to directly compare remimazolam and dexmedetomidine for sedation in ESRD patients undergoing procedural sedation. The results of this study will provide valuable insights into optimizing sedation strategies in this high-risk population, potentially improving clinical outcomes by minimizing complications associated with drug metabolism and recovery. TRIAL REGISTRATION: Chinese Clinical Trial Registry. chictr.org.cn ChiCTR2300075278. Registered on August 31, 2023. https://www.chictr.org.cn/showproj.html?proj=205061 .
Guideline for the Measurement, Analysis and Reporting of Medication Adherence during the Run-in phase of clinical trials (MARMAR).
Davies N, Vrijens B, Wright DFB … +1 more , Hughes DA
Trials · 2026 Apr · PMID 41987203 · Full text
BACKGROUND: Trial run-in phases are sometimes used to select participants into clinical trials who are most likely to remain adherent to study medications. The study designs and data analysis methods employed lack clear...
BACKGROUND: Trial run-in phases are sometimes used to select participants into clinical trials who are most likely to remain adherent to study medications. The study designs and data analysis methods employed lack clear regulatory guidance while reporting is not consistent or transparent. This study aims to develop a consensus guideline for the Measurement, Analysis, and Reporting of Medication Adherence during the Run-in phase (MARMAR) of clinical trials. METHODS: Initial "items" (specific statements relating to the measurement, analysis, and reporting of medication adherence during trial run-in phases) were generated following a systematic review of trial run-in phases. Items were split into 2 domains (methods and reporting), refined through a pilot exercise and subsequently evaluated using a two-round modified Delphi survey of international experts in medication adherence and clinical trials. Participants were recruited via e-mailing lists. In survey round one, respondents rated the importance of items across a scale labelled strongly agree to strongly disagree and provided free-text comments. In survey round two, respondents categorised items as essential or desirable and suggested alternative wording. A final consensus meeting of the research team was held to finalise the guideline. Guideline development was endorsed by the International Society for Medication Adherence (ESPACOMP) and registered with EQUATOR. RESULTS: In round one, 49 respondents rated 29 items, with 64-100% (mean 86.5%) of experts scoring an item 4 or 5. Consensus was reached for 28 items, and 226 free-text comments led to merging overlapping items. In round two, 27 respondents rated 20 revised items, with 33-100% (mean 78.7%) of experts judging them essential and providing 66 free-text comments. The final MARMAR guideline comprises 20 items: 9 methodological and 11 reporting considerations for medication adherence during trial run-in phases. CONCLUSION: The MARMAR guideline provides the first structured, consensus-based guideline specifically focused on medication adherence during trial run-in phases. By supporting more transparent and rigorous measurement, analysis and reporting, it should serve to improve the quality of future trial run-in phases.
Losartan to Improve Outcomes after multi-ligament kNee injury (LION Trial).
Kehoe S, Stone A, Yuan X … +16 more , Conley C, Hawk G, Smith S, Zgoda M, Corey N, Johnson D, Wilson B, Zhou L, Berkson E, Goertz S, Huff L, Hutchinson I, Matzkin E, Richardson L, Lattermann C, Jacobs C
Trials · 2026 Apr · PMID 41981668 · Full text
BACKGROUND: Multi-ligament knee injuries (MLKI) are complex injury patterns that affect two or more ligaments of the knee. Although surgical intervention can improve functional and clinical outcomes, a large percentage o...
BACKGROUND: Multi-ligament knee injuries (MLKI) are complex injury patterns that affect two or more ligaments of the knee. Although surgical intervention can improve functional and clinical outcomes, a large percentage of patients are unable to return to preoperative activity levels. One reason for this is loss of knee range of motion (ROM), which characterizes the exaggerated pro-inflammatory environment of arthrofibrosis and is associated with future osteoarthritis risk. The purpose of this study is to assess the effectiveness of a 30-day course of losartan, a common angiotensin II antagonist, in improving surgical outcomes one year after MLKI surgery by reducing arthrofibrosis and pro-inflammatory signaling. Our hypothesis is that individuals who undergo MLKI reconstruction and take losartan will report an increased ability to return to activity, improved ROM, and decreased synovitis. METHODS: This is a randomized, double-blinded, placebo-controlled clinical trial that aims to recruit 90 patients who are undergoing MLKI reconstruction. Upon enrollment, patients will be randomly assigned to a 30-day postoperative course of oral losartan or placebo on a 1:1 basis. The primary outcome will be the Cincinnati Occupational Rating Scale (CORS) Questionnaire Score which will quantify self-reported physical function. The secondary outcomes will include the time to return to active duty, work, and/or sport after surgery; International Knee Documentation Committee (IKDC) Subjective Knee Scores; Visual Analogue Scale (VAS) Pain Scores; knee ROM; quadricep strength; and ultrasound measures of persistent synovitis. DISCUSSION: There is an unmet need for interventions to reduce inflammation and arthrofibrosis following MLKI to both rescue ROM and improve rates of return to activity. The LION Trial is a randomized, placebo-controlled clinical trial that will evaluate the efficacy of a 30-day course of losartan following MLKI reconstruction. The results of this study have the potential to redefine perioperative management and improve long-term functional outcomes for all patients undergoing ligament reconstruction with a widely available and inexpensive medication. TRIAL REGISTRATION: Clinicaltrials.gov #NCT06933706. Registered on April 11th, 2025.
Development of artificially intelligent tool for analysis and prediction of myopia progression among school-going children.
Singh P, Verma V, Karkhur S … +3 more , Beri A, Singhai J, Agrawal DK
Trials · 2026 Apr · PMID 41981408 · Full text
BACKGROUND: Myopia is a growing public health concern among school-going children, with increased screen time and reduced outdoor activities contributing to its early onset and rapid progression. In India, the absence of...
BACKGROUND: Myopia is a growing public health concern among school-going children, with increased screen time and reduced outdoor activities contributing to its early onset and rapid progression. In India, the absence of a standardized, population-based dataset reflecting socio-economic and environmental diversity limits the development of accurate prediction tools. This study aims to design and validate an artificial intelligence (AI)-based model to analyze and predict myopia progression among children aged 6 to 18 years in urban and rural areas. METHODS: This is a prospective, community-based study conducted in two phases across five districts of Bhopal division, India. Phase one involves a cross-sectional survey of approximately 5,000 school children to collect demographic and ocular health data, including visual acuity, refractive error, axial length, corneal parameters, and lifestyle factors. In phase two, a longitudinal cohort comprising 10% of the phase one participants (balanced for existing and non-existing myopia cases) will be followed every 6 months over 2 years. Machine learning algorithms, including linear regression, support vector machines, XGBoost, and deep learning models such as convolutional neural networks, will be trained on this dataset. An AI-based mobile application will be developed to enable field-level prediction and screening. DISCUSSION: This study will generate the first large-scale Indian dataset on myopia progression among children, incorporating diverse socio-economic backgrounds. The validated AI model and mobile application will support early identification of at-risk children, optimize resource allocation, and inform national screening strategies. By integrating real-time data analytics with field-l. TRIAL REGISTRATION: CTRI/2025/07/091243. Registered on 21/07/2025.
Clinical efficacy of intermittent theta burst stimulation in the acute phase of adolescent depression: study protocol of a double-blind, randomized controlled trial.
Ye Q, Yang Y, Cai W … +2 more , Wen J, Lan Y
Trials · 2026 Apr · PMID 41975503 · Full text
BACKGROUND: Adolescent depression is a significant health problem, and developing safe and rapid treatments for it is crucial. Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic...
BACKGROUND: Adolescent depression is a significant health problem, and developing safe and rapid treatments for it is crucial. Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), enhances synaptic transmission and cortical excitability by simulating cortical rhythms and has demonstrated certain therapeutic effects in adults. Adolescents in the acute phase of depression present with more severe symptoms and are pressed for time, so a short, effective modality like iTBS could be particularly advantageous. However, studies on the effects of iTBS during the acute phase of adolescent depression are still fairly limited. Therefore, this study aims to explore the clinical efficacy of iTBS in adolescents with depression during the acute phase through a viable research design. METHODS: This is a single-center, randomized, double-blind, and sham-stimulation-controlled clinical trial. We plan to recruit approximately 76 adolescent patients with depression aged 14-18 years. Eligible participants will be randomly assigned to the treatment group (n = 38) or the sham control group (n = 38). Each participant will receive 10 sessions of iTBS over 10 days, delivered at 80% of the active threshold, with 1,800 pulses per session. The treatment target will be the left dorsolateral prefrontal cortex. Clinical and neurophysiological assessments will be conducted at baseline, at the end of treatment, and during follow-up at weeks 2 and 4 after treatment completion. Safety will be monitored through semi-structured interviews and the reporting of adverse events. DISCUSSION: Conventional rTMS treatment faces logistical challenges due to its standard course requiring daily treatment over 4-6 weeks. This study aims to explore a safe and effective iTBS protocol for adolescent patients with depression to complement existing treatments. By evaluating clinical symptoms and the most sensitive neurophysiological features after treatment, we hope to optimize the iTBS protocol. This study aims to reduce the treatment duration, alleviate the economic burden on families and society, and expedite the clinical response for adolescent patients. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry. REGISTRATION NUMBER: ChiCTR2500101152. Retrospectively registered on 21 April 2025.
C5-C6 and thoracic spine mobilization with postural correction exercise compared with conventional therapy in patients with adhesive capsulitis: a two-group, parallel-arm, single-blinded, randomized clinical trial-study protocol.
Arulsingh W, de Sá Ferreira A, Kandakurti PK … +1 more , Patil SS
Trials · 2026 Apr · PMID 41975488 · Full text
INTRODUCTION: Adhesive capsulitis (AC) often resolves independently but can persist for years and may not fully improve. The most effective treatments for AC are not well established. Although the shoulder girdle muscles...
INTRODUCTION: Adhesive capsulitis (AC) often resolves independently but can persist for years and may not fully improve. The most effective treatments for AC are not well established. Although the shoulder girdle muscles are primarily controlled by the cervical nerve roots, particularly C5 and C6, research linking these roots to the pathogenesis of AC is currently lacking. While existing studies suggest a connection between thoracic mobility, posture, and shoulder mobility, the potential benefits of mobilizing the C5-C6 region and thoracic spine, in conjunction with postural correction exercises for treating AC, have yet to be explored. OBJECTIVES: This study protocol will be to assess the effectiveness of C5-C6 and thoracic spine mobilization combined with postural correction exercises, compared to conventional therapy, in alleviating pain, improving range of motion (ROM), and reducing disability in patients with AC. METHODS: This study will be a two-group, randomized controlled trial with assessors blinded to group assignments. A total of 66 adults with AC will be randomly allocated into two groups: the experimental group (n = 33), which will undergo C5-C6 and thoracic spine mobilization along with postural correction exercises, and the control group (n = 33), which will receive conventional therapy, for 3 weeks. The primary outcomes will include shoulder pain, shoulder joint range of motion, and the Disability Index, all of which will be assessed at baseline, immediately post-intervention, and 3 months after randomization. An intention-to-treat approach will be employed for the analysis. Additionally, a sensitivity analysis will be performed using a per-protocol approach to examine the potential impact of incomplete adherence and participant dropout. Linear mixed models will be applied to investigate the main effects and interactions of the group and time on the study outcomes, adjusting for covariates such as age, sex, duration of condition, and presence of comorbidities. Multiple imputation methods will be utilized to address any missing data. DISCUSSION: This study's findings will help assess the effectiveness of spinal manual therapy combined with postural correction exercises in patients with AC compared to traditional physiotherapy. Additionally, the prognostic value of AC may be improved based on these results. We will track the treatment outcomes through immediate, short-term, and mid-term follow-ups. TRAIL REGISTRATION: ClinicalTrials.gov NCT06449261. This study protocol is Version 1.0, dated 07 June 2024.
Efficacy, safety, and cost-effectiveness of Sophora flavescens films in the treatment of postpartum vaginal dysbiosis in women (SFF-PVD Study): study protocol for a multicenter double-blind randomized controlled trial.
Huang Y, Tan S, Li X … +12 more , Pan Y, Yang Z, Sun S, Lan J, Zhang R, Zhao H, Hu L, Wang J, Zheng W, He R, Zeng X, Zhang J
Trials · 2026 Apr · PMID 41975446 · Full text
BACKGROUND: The vaginal microecological barrier in postpartum women is particularly vulnerable, and its stability plays a crucial role in maintaining reproductive tract health. Emerging evidence indicates that Sophora fl...
BACKGROUND: The vaginal microecological barrier in postpartum women is particularly vulnerable, and its stability plays a crucial role in maintaining reproductive tract health. Emerging evidence indicates that Sophora flavescens films (SFF) may have therapeutic potential in managing postpartum vaginal dysbiosis (PVD). This study is therefore designed to evaluate the safety, efficacy, and cost-effectiveness of SFF in the treatment of PVD. METHODS AND ANALYSIS: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 292 participants diagnosed with PVD will be enrolled from four tertiary hospitals across China. Eligible participants will be randomly assigned to receive either SFF or a placebo, administered intravaginally once daily for seven consecutive days (each film contains 100 mg of oxymatrine). The primary outcome is the therapeutic efficacy of SFF in improving PVD. Secondary outcomes include changes in vaginal health scores, vaginal inflammation scores, quality of life, levels of vaginal inflammatory biomarkers, incidence of adverse events, and treatment-related costs. Multivariable logistic regression models and analysis of covariance (ANCOVA) will be employed for analysis. Furthermore, a cost-effectiveness analysis (CEA) from the patient's perspective will be performed using a decision tree model to evaluate the pharmacoeconomic profile of SFF. DISCUSSION: This study provides evidence-based insights into clinical interventions for PVD. It uses standardized assessment criteria and a double-blind design. However, the findings may be influenced by subjective judgment and regional limitations. Future multicenter studies are needed. They will validate therapeutic efficacy. This will help optimize clinical decision-making and economic evaluations. TRIAL REGISTRATION: The study is registered at http://www.chictr.org.cn (ChiCTR2500102388, 14 May 2025).
Effect of brief online mindfulness-based cognitive therapy in patients with digital replantation: a study protocol for a randomized controlled trial.
Huang F, Wang W, Miao X … +4 more , You M, Liu M, Tang W, Lu J
Trials · 2026 Apr · PMID 41975444 · Full text
BACKGROUND: Traumatic amputations are common traumatic injuries that require digital replantation to restore the form, function, and sensation of the hand. The post-surgical survival of replanted digits is influenced by...
BACKGROUND: Traumatic amputations are common traumatic injuries that require digital replantation to restore the form, function, and sensation of the hand. The post-surgical survival of replanted digits is influenced by multiple factors, including psychological factors such as posttraumatic stress disorder (PTSD), anxiety, and depression. Mindfulness-based cognitive therapy (MBCT) is considered a potential intervention to address such emotional distress. Traditionally, MBCT involves an 8-week face-to-face group format. Due to feasibility concerns regarding implementation and patient adherence, this study proposes a modified 4-week online version, referred to as brief online MBCT (eMBCT). METHODS: This study is a two-arm randomized controlled clinical trial. The control group will receive standard postoperative nursing care, while the intervention group will receive the eMBCT for 4 weeks. The primary outcome measure is PTSD symptom severity, assessed using the Stanford Acute Stress Reaction Questionnaire (SASRQ). Secondary outcomes include the Connor-Davidson Resilience Scale (CD-RISC), the General Self-Efficacy Scale (GSES), the EuroQol Five-Dimensional Health Scale (EQ-5D), and postoperative recovery status. DISCUSSION: This study aims to investigate the effects of a brief eMBCT program on PTSD symptoms, psychological resilience, self-efficacy, and clinical outcomes-specifically the incidence of vascular crisis and hand function recovery-in patients undergoing digital replantation. TRIAL REGISTRATION: ChiCTR2500101285 [Chinese Clinical Trial Registry; registered on 23 April 2025].
Early lumbar drainage plus intrathecal urokinase in severe aneurysmal subarachnoid hemorrhage: the LD-ITUK randomized controlled trial protocol.
Wu M, Yan T, Hu P … +13 more , Wang C, Ye M, Yu Z, Wang Y, Mao G, Xiao B, Gong Y, Li J, Zhao R, Yang P, Liu J, Zhu X, LD-ITUK Investigators
Trials · 2026 Apr · PMID 41968344 · Full text
BACKGROUND: Despite advances in embolization techniques and neurocritical care, patients with severe aneurysmal subarachnoid hemorrhage (SaSAH) continue to face substantial risk of morbidity and long-term disability. The...
BACKGROUND: Despite advances in embolization techniques and neurocritical care, patients with severe aneurysmal subarachnoid hemorrhage (SaSAH) continue to face substantial risk of morbidity and long-term disability. The presence of subarachnoid blood and its breakdown products significantly contributes to secondary brain injury and subsequent complications. Although the EARLYDRAIN trial demonstrated a benefit from lumbar drainage in clearing blood, this method alone is insufficient to remove clots located above the fourth ventricle. Urokinase, a fibrinolytic agent, offers a potential means to enhance clot clearance. However, the combined strategy of lumbar drainage plus intrathecal urokinase (LD-ITUK) has not yet been rigorously evaluated. METHODS/DESIGN: This is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled superiority trial. It aims to compare the efficacy of LD-ITUK against lumbar drainage alone (with intrathecal saline) in patients with SaSAH, when added to standard care. A total of 424 eligible patients will be randomized in a 1:1 ratio to receive either the intervention (LD-ITUK) or the control treatment (lumbar drainage plus intrathecal saline). Eligible participants are adults with a first-episode aSAH, clinically graded as Hunt-Hess III to V, whose ruptured aneurysm has been secured via surgical clipping or endovascular coiling within 48 h after onset. The primary outcome is the proportion of patients achieving a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 2 at 180 days after onset, as adjudicated by an independent Outcome Adjudication Committee (OAC) blinded to treatment allocation. DISCUSSION: This trial will determine whether the LD-ITUK method could improve the long-term functional outcomes compared to the current standard treatment in patients with SaSAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT06284642. Registered 28 February 2024.
Group cognitive evolutionary therapy for depression: a protocol for a randomized controlled trial.
Dobrovolschi M, Giosan C
Trials · 2026 Apr · PMID 41965820 · Full text
BACKGROUND: Depression ranks among the most widespread mental disorders globally and is a leading cause of disability. Despite increasing research efforts and substantial financial investment, the incidence of depression...
BACKGROUND: Depression ranks among the most widespread mental disorders globally and is a leading cause of disability. Despite increasing research efforts and substantial financial investment, the incidence of depression continues to rise. This study aims to evaluate the effectiveness of Cognitive Evolutionary Therapy (CET) delivered in a brief group therapy format for treating mild to moderate depression. METHODS: This randomized controlled trial will compare two conditions-CET group therapy and a waitlist control-at three time points: pre-treatment, post-treatment, and a 3-month follow-up. The study will include 64 Romanian participants aged 18 to 65 with mild to moderate depression. DISCUSSION: Group therapy may enhance the processing of distal causes of depression by leveraging their universal and social nature, potentially increasing the efficacy of CET. If successful, these findings could lead to the development of more efficient and time-saving therapeutic protocols for depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06359769, version 03/04/2026. Registered on June 04, 2024.
Impact of using routine healthcare data on the efficiency of implementation trials: a qualitative comparative case study.
Xie CX, Toader AM, De Simoni A … +4 more , Eldridge S, Glass JE, Pinnock H, Relton C
Trials · 2026 Apr · PMID 41965800 · Full text
BACKGROUND: Randomised implementation trials evaluate the effects of implementation strategies on implementation outcomes and may also monitor clinical effectiveness. Routine healthcare data are used in implementation tr...
BACKGROUND: Randomised implementation trials evaluate the effects of implementation strategies on implementation outcomes and may also monitor clinical effectiveness. Routine healthcare data are used in implementation trials for participant identification, intervention delivery, and/or outcome ascertainment. Trial efficiency (scientific, operational, statistical, and economic) is operationalised across trial design, processes, superstructure, infrastructure, and stakeholder engagement (the Trial Efficiency Pentagon). Despite frequent usage, the contribution of routine data to implementation trial efficiency remains underexplored. We aimed to investigate how the use of routine healthcare data affects trial efficiency in two implementation trials. METHODS: We conducted a qualitative comparative case study of two implementation trials, one UK-based and one US-based. Participants were purposively sampled from trial teams involved in the use and management of routine healthcare data. Data were collected through semi-structured interviews, document analysis, and feedback workshops. Framework analysis guided by the Trial Efficiency Pentagon was used to analyse the data, and data flow diagrams were developed to visualise routine data pathways within each trial. RESULTS: The two trials (DIGITS and IMPART) used routine data to characterise the practice population of eligible patients, support clinical and economic outcome evaluation, facilitate audit and feedback, and assist in intervention delivery. Common facilitators that supported the use of routine data included sufficient IT and hardware capacity, relatively low cost, centralised regulatory approval for multi-site studies, and strong collaboration and partnerships. Common barriers included administrative complexity, redundant bureaucratic processes, and challenges with data sharing requirements. Key differences included the DIGITS trial's in-house data warehouses within an integrated healthcare system ensured high data quality and enabled preliminary analyses. In contrast, the IMPART trial, managing a larger national sample, employed an external research database to integrate data from various EHR systems but faced challenges such as legacy systems, diverse coding practices and site-specific approvals. Data quality can act as either a facilitator or a barrier. CONCLUSIONS: Routine data has an impact on implementation trial efficiency across trial design, processes, superstructure, infrastructure, and stakeholder engagement. To improve trial efficiency in public healthcare systems, researchers must address technological and regulatory barriers to accessing data. In private healthcare systems, data use and access hinges on investing in robust IT infrastructure and ensuring comprehensive organisational commitment. TRIAL REGISTRATION: IMPART trial registration: ISRCTN15448074; DIGITS trial Clinicaltrials.gov Identifier: NCT05160233.
Remimazolam versus midazolam for sedation in diagnostic upper gastrointestinal endoscopy: study protocol for a randomized controlled trial.
Ahn DW, Lee JK, Lee KH … +5 more , Kim T, Kang SH, Park Y, Kim SB, Kim SJ
Trials · 2026 Apr · PMID 41965699 · Full text
BACKGROUND: Remimazolam is a new alternative drug combining the efficacy and safety advantages of midazolam and propofol. However, studies comparing remimazolam with midazolam in diagnostic upper gastrointestinal endosco...
BACKGROUND: Remimazolam is a new alternative drug combining the efficacy and safety advantages of midazolam and propofol. However, studies comparing remimazolam with midazolam in diagnostic upper gastrointestinal endoscopy are insufficient. The purpose of this study was to prove the efficacy and safety of remimazolam in diagnostic upper gastrointestinal endoscopy compared with midazolam. METHODS: This study is a randomized, controlled, multicenter trial. Participants who are to receive diagnostic upper gastrointestinal endoscopy are enrolled and randomly assigned to the remimazolam or midazolam group (control group) at a 1:1 ratio. Remimazolam is given (with an initial 5 mg plus an additional 2.5 mg, maximum 5 times) in the remimazolam group for endoscopic sedation and midazolam is given (with an initial 2 mg plus an additional 1~2 mg, maximum 5 times) in the control group. Flumazenil can be given at the discretion of the investigator. Vital signs, level of consciousness, and adverse events are assessed from the administration of sedatives to the full recovery of consciousness. The primary endpoint is total procedure time, which is defined as the time from the first administration of sedatives to discharge. The secondary endpoints include the success rate of sedation, recovery time, induction time, total endoscopy time, discharge time, sedation time, incidence of hypotension, respiratory depression, tachycardia, bradycardia, participant satisfaction, and paradoxical response incidence. DISCUSSION: The results of this trial are expected to prove the superior efficacy of remimazolam with favorable safety. Based on the results, a sedation method using remimazolam would be applied preferentially for diagnostic upper gastrointestinal endoscopy in clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov NCT05836545. Registered on April 19, 2023.
Impact of the POPulation Medicine Multimorbidity Intervention in Xishui County (POPMIX) on suspected asthma patients: protocol for the POPMIX-Asthma cluster-randomized controlled trial.
Huang K, Tong X, Tang X … +23 more , Lai Q, Liu Y, Zhang S, Zheng Z, Chen W, Cao Z, Tang L, Zhao J, He L, Jiao L, Wang Y, Zhao T, Luo Y, Lyu X, Chen Q, Vollmer S, Geldsetzer P, Jamison D, Bärnighausen T, Chen S, Wang C, Yang T, POPMIX study investigators
Trials · 2026 Apr · PMID 41964072 · Full text
BACKGROUND: Asthma is a common chronic disease responsible for a considerable disease burden in China and around the world. Despite its burden, there is substantial unmet need for asthma care, including screening, diagno...
BACKGROUND: Asthma is a common chronic disease responsible for a considerable disease burden in China and around the world. Despite its burden, there is substantial unmet need for asthma care, including screening, diagnosis, treatment, and management. Symptom-based screening for asthma could support identification of undiagnosed asthma patients, as well as reference to higher-level hospitals for formal diagnoses and treatment. This study focuses on identifying suspected asthma patients and encouraging them to seek formal diagnoses and treatment. This approach aligns with the novel concept of population medicine, which aims to maximize overall population health rather than focusing on individual patients within the health system. METHODS: We are conducting a two-arm population-based stratified clustered randomized controlled trial (cRCT) to evaluate the effectiveness of a population medicine multimorbidity intervention package. The intervention integrates community screening, chronic disease management, patient education, digital follow-up, and team-based care. The trial is being implemented in Xishui County, Guizhou Province, a mountainous low-resource county in Southwestern China, covering 26 townships and more than 300,000 permanent residents. We considered each of the 26 townships in Xishui County as a cluster and stratified them into large and small townships based on population size. Townships with an above-average population were designated as "large," and those with a below-average population were designated as "small." We randomized the same number of residents in each township stratum (large and small) to undergo the European Community Respiratory Health Survey (ECRHS) for identifying suspected asthma patients. Individuals identified as suspected asthma patients were considered study participants and subsequently enrolled in the intervention or control arm. All participants in the intervention arm are followed for one year, with one telephone follow-up at month three and in-person follow-ups at months six and 12, while participants in the control arm are followed only at baseline and 12 months. Primary outcomes include the number of chronic conditions controlled, whether the participant received lung function testing, and Asthma Control Test (ACT) score. In addition, we are evaluating 42 secondary outcomes covering physiological and functional indicators such as lung function, health-related quality of life, mental health, behavioral risk factors, healthcare utilization, productivity loss, knowledge of asthma and chronic obstructive pulmonary disease (COPD), and care cascade indicators for asthma and other chronic diseases. DISCUSSION: This cRCT has been featured as an important case study in the Lancet Commission on Investing in Health report to evaluate the effectiveness of the integrated intervention package on priority conditions. The trial was designed under population medicine principles, with an aim providing holistic care and enhancing the overall health status of suspected asthma patients. The results of the trial will inform the next generation of multimorbidity management and population medicine practices among global health authorities and practitioners. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06457009. Registered on June 7, 2024.
Nintedanib in progressive bronchiolitis obliterans syndrome (BOS) grade 0p-1-2 in lung transplant recipients (INFINITIx-BOS): protocol of a French multicenter randomized controlled trial.
Brugière O, Hirschi S, Reynaud-Gaubert M … +8 more , Bunel V, Demant X, Le Pavec J, Falque L, Si Mohammed N, Tardivon C, Couffignal C, INFINITIx-BOS Consortium
Trials · 2026 Apr · PMID 41964069 · Full text
BACKGROUND: Long-term survival after lung transplantation (LTx) is still hampered by the development of chronic allograft dysfunction (CLAD). Bronchiolitis obliterative syndrome (BOS), the most common phenotype of CLAD,...
BACKGROUND: Long-term survival after lung transplantation (LTx) is still hampered by the development of chronic allograft dysfunction (CLAD). Bronchiolitis obliterative syndrome (BOS), the most common phenotype of CLAD, is thought to arise from repeated injuries to graft epithelial cells, leading to fibrous scarring of small airways. Thus far, there is no approved treatment for BOS disease. Based on both animal/human studies in LTx and the demonstrated efficacy of the TKI nintedanib treatment in idiopathic pulmonary fibrosis (IPF), nintedanib is a candidate molecule capable of stopping the fibroproliferative process in BOS. Hence, the rationale to conduct a nintedanib trial in LTx recipients with BOS is based on (i) an unmet medical need due to poor survival after BOS diagnosis; (ii) the demonstrated fibrotic pathways in BOS; and (iii) the proven efficacy of nintedanib in IPF. METHODS: The INFINITIx-BOS study is an investigator-initiated, national multicentric, phase II, superiority, parallel-group, double-blind, comparative randomized clinical trial. A total of 80 recipients with progressive BOS within the prior year, at least at 6 months post-LTx, will be randomized to receive either nintedanib (150 mg bid) or placebo for a period of 6 months, in addition to maintenance immunosuppressive therapy left to their physician's discretion with 4 dedicated visits. The primary endpoint is the slope of decline over 6 months of treatment. The secondary endpoints are change in 6-min walk test, SGRQ, graft failure, SPO2, and safety events over 6 months, which will be compared between the two arms. DISCUSSION: Based on a fibrotic pattern partially shared between IPF and BOS, this randomized INFINITIx-BOS trial has the potential to demonstrate an additional strategy with nintedanib as a targeted-fibrotic pathway associated with BOS. TRIAL REGISTRATION NUMBER: NCT03283007, first posted 11 September 2017. Protocol version identifier No. 6-0, 8 September 2023.
The power, potential of real-world data in randomized controlled trials: proceedings from a multistakeholder think tank.
Nouhravesh N, Jackman JG, Hernandez AF … +10 more , Lee C, Hornik CP, Zacherle E, Waldstreicher J, Cocoros N, Brown S, Biering-Sorensen T, Chiswell K, Wruck L, James SK
Trials · 2026 Apr · PMID 41963997 · Full text
Randomized controlled trials (RCTs) remain the gold standard for evaluating medical interventions, but they often face challenges related to patient recruitment, cost, and efficiency. Real-world data (RWD) has emerged as...
Randomized controlled trials (RCTs) remain the gold standard for evaluating medical interventions, but they often face challenges related to patient recruitment, cost, and efficiency. Real-world data (RWD) has emerged as a valuable tool to enhance trial design, improve patient identification, and support regulatory decision-making. However, integrating RWD into RCTs presents methodological, regulatory, and operational challenges. To address these issues, a think tank was convened in May 2024 at the Duke Clinical Research Institute, bringing together experts from academia, industry, healthcare systems, regulatory agencies, and patient advocacy groups. Discussions focused on three key areas: optimizing patient identification and outcome assessment, leveraging RWD for safety assessments, and using RWD in RCTs supporting regulatory approval. RWD has the potential to simplify eligibility criteria, enhance recruitment through artificial intelligence, and provide practical endpoints for evaluating treatment effects. The think tank underscored the need for collaboration across stakeholders to address challenges, such as data inconsistencies, privacy concerns, and infrastructure limitations. The event concluded with actionable recommendations, including the following: (1) standardizing RWD sources to ensure consistency and improve interoperability across healthcare systems, (2) developing regulatory frameworks that define acceptable use cases for RWD in clinical trials, (3) enhancing data quality through robust validation methodologies and real-time monitoring, (4) investing in artificial intelligence-driven patient identification tools to streamline recruitment, and (5) fostering multi-stakeholder collaboration to align expectations and share best practices. Moving forward, implementing these strategies will be critical to fully harness the potential of RWD in clinical research and improve trial efficiency.
Effect of distant-image screen technology (DIST) on delaying myopia onset in pre-myopia children: study protocol for a1-year randomized controlled trial.
Zou L, Li X, Zhou J … +1 more , Xu M
Trials · 2026 Apr · PMID 41963994 · Full text
BACKGROUND: Myopia is an escalating global health issue, particularly among adolescents, and its increasing prevalence is associated with a rising burden of ocular complications that adversely affect quality of life and...
BACKGROUND: Myopia is an escalating global health issue, particularly among adolescents, and its increasing prevalence is associated with a rising burden of ocular complications that adversely affect quality of life and strain healthcare resources. Extensive evidence links prolonged near work to myopia progression, prompting the development of innovative control strategies. One promising approach is the distant-image screen (DIST), which transforms a nearby real image into a virtual one that appears much farther away, thereby reducing the accommodative stress typically induced by prolonged near work. This study is designed to evaluate the efficacy of DIST in delaying the onset of myopia among pre-myopic children. METHODS: This is a 1-year, multi-arm randomized controlled trial involving 192 children, who will be randomly assigned in a 1:1:1 ratio to one of three groups: (1) a DIST group; (2) a Combined Intervention group, which will receive both DIST and an optical defocusing intervention; and (3) a control group, engaging in regular near work without the use of DIST. The primary objective is to assess whether the use of DIST-alone or in combination with optical defocusing-can effectively delay the onset of myopia in pre-myopic children. The primary outcome is the proportion of myopia onset, and the secondary outcomes are the proportion of fast myopia progressors, change in spherical equivalent progression, and change in axial length at each follow-up point. DISCUSSION: The study aims to determine the independent efficacy of DIST as well as its potential synergistic benefits when combined with optical defocusing techniques. In the context of increasing academic demands and near work exposure, DIST offers a space-efficient, practical solution that could alleviate visual strain without interfering with learning. By providing robust data on both refractive and ocular structural changes, the findings may inform personalized myopia prevention strategies. If successful, DIST could serve as a valuable adjunct to current myopia control methods, ultimately reducing the public health burden of myopia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2400082078. Registered on 20 March 2024. https://www.chictr.org.cn/showproj.html?proj=221835 .
Intensive Interaction for children and young people with profound and multiple learning disabilities (INTERACT): study protocol for a cluster randomised controlled trial, economic evaluation and process evaluation.
Bell KJ, Bradshaw J, Clegg J … +21 more , Whiteside K, Baird K, Peck C, Scantlebury A, Wang HI, Adamson J, Allard A, Blackwell JE, Carlisle K, Fountain I, Gore N, Kyffin F, Miller J, Okanlawon A, Pennington L, Robinson-Smith L, Ronaldson S, Standley E, Sweeney J, Ziegler L, Hewitt C
Trials · 2026 Apr · PMID 41957844 · Full text
BACKGROUND: Communication interventions can facilitate communication between people with profound and multiple learning disabilities (PMLD) and familiar partners such as family and educational setting staff, including sp...
BACKGROUND: Communication interventions can facilitate communication between people with profound and multiple learning disabilities (PMLD) and familiar partners such as family and educational setting staff, including speech and language therapists. Various communication interventions are routinely used but their clinical and cost-effectiveness are unclear. Intensive Interaction (II) is one intervention that focuses on early interaction abilities. II can be delivered by staff in educational settings and/or at home. Despite many settings already implementing II, staff are sometimes untrained or have not received up to date training, potentially leading to inconsistencies in how the technique is applied and the quality of the interactions. We will provide structured training in II to educational setting staff and parents/carers with coordinated activities developed jointly for each child/young person to be delivered within the educational setting and at home. This study aims to establish whether Intensive Interaction delivered within educational settings improves communication skills of children and young people with PMLD. METHODS: A multi-site pragmatic cluster randomised controlled trial comparing usual care with Intensive Interaction and usual care. Clusters will be educational settings. This study will recruit 330 participants (aged 3-25 years) with PMLD from 66 educational settings within Great Britain. Each participant will have a corresponding teacher, parent/carer, and interventionist. Potential participants will be screened by their educational setting for eligibility prior to giving informed consent. Data will be collected at baseline, 32 weeks, and 52 weeks post-randomisation and will assess health and educational outcomes including participants' communication skills, behaviour, wellbeing, and quality of life. The primary outcome is communication skills, measured by the Communication Complexity Scale (CCS) at 32 weeks post-randomisation. Setting staff will video record an interaction with each participating child/young person. Communication will be coded by members of the research team blinded to allocation using the CCS. DISCUSSION: This study addresses a much used but currently under-researched intervention and results will inform the support provided to children and young people with PMLD in their educational settings and at home. TRIAL REGISTRATION: The trial was prospectively registered on the ISRCTN registry on 3rd May 2023 (registration number: ISRCTN81099965, https://www.isrctn.com/ISRCTN81099965 ).
Improving social functioning in people with substance use and mental health disorders using virtual reality (ROPVR): study protocol for a multi-center, pragmatic randomized controlled trial.
Bech AB, Wechsler TF, Mühlberger A … +2 more , Lien L, Leonhardt M
Trials · 2026 Apr · PMID 41957842 · Full text
BACKGROUND: In individuals with substance use disorders (SUDs), impairment of social, occupational, and/or recreational functioning is common. Social functioning encompasses social skills, social behavior, and cognitive...
BACKGROUND: In individuals with substance use disorders (SUDs), impairment of social, occupational, and/or recreational functioning is common. Social functioning encompasses social skills, social behavior, and cognitive skills, which are relevant for establishing meaningful relationships and effective functioning across different domains in life. The main aim of the study is to determine the effectiveness of tailored virtual reality (VR) social functioning training as an adjunct to in-patient SUD treatment in improving functionality, measured by World Health Organization Disability Assessment Scale 2.0 at 6 months post-intervention. METHODS: The study is designed as a two-arm, statistician-blinded, pragmatic, multi-cite, randomized controlled trial. Eligible participants will be randomly assigned to either the intervention or control group using 1:1 allocation. The control group receives standard in-patient SUD treatment, and the intervention group receives additionally VR social functioning training (8 sessions). Both the intervention and control groups will be assessed for between-group differences in functioning change from before randomization (T0), to 6-week (T1), and to 6-month (T2). Both groups will also be assessed before (T0), at 6-month (T2), and at 12-month follow-up (T3) for a health economic evaluation. DISCUSSION: Evidence suggests that VR training can enhance patients' social functioning and thereby improve relations and promote community participation in people with SUD. To the best of our knowledge, this is the first study that aim to explore the use of VR in improving social functioning in patients with SUD. Thus the results of this trial can provide valuable insights for clinicians and health authorities. TRIAL REGISTRATION: ClinicalTrials.gov NCT06677515. Registered on November 11, 2024.
Applying a hypothetical strategy to the intercurrent event of non-adherence with the parametric g-formula: a post hoc secondary analysis of the MET-PREVENT randomised controlled trial.
Hiu S, Wilson N, Wilson K … +4 more , Lin N, Witham MD, Wason JMS, M. E. T.-PREVENT Study Group
Trials · 2026 Apr · PMID 41957819 · Full text
BACKGROUND: We conducted a post hoc secondary analysis of the MET-PREVENT randomised placebo-controlled trial to target an estimand that uses a hypothetical strategy on the intercurrent event of non-adherence. METHODS: W...
BACKGROUND: We conducted a post hoc secondary analysis of the MET-PREVENT randomised placebo-controlled trial to target an estimand that uses a hypothetical strategy on the intercurrent event of non-adherence. METHODS: We viewed the targeting of this estimand that uses a hypothetical strategy to handle the intercurrent event of non-adherence as a type of causal mediation problem, where randomised treatment is a binary exposure, adherence is a binary mediator, there is an exposure-mediator interaction, and mediator-outcome confounders that are caused by the exposure (e.g. gastrointestinal symptoms) are present. We used the parametric g-formula to estimate the average controlled direct effect (CDE) of metformin (versus placebo) on 4-m walk speed, which is interpreted as the average treatment effect under the hypothetical scenario that all trial participants adhered to assigned treatment. Variables identified as confounders were informed by a literature review and discussions with an expert; assumptions about the causal structure were represented in a directed acyclic graph. We applied a probabilistic bias analysis (PBA) to understand the potential for bias assuming adherence had been misclassified; observed adherence based on returned tablet count may be an inaccurate version of "true adherence" based on actual consumption. RESULTS: Our sample size was 70 trial participants (34 metformin, 36 placebo). Our estimate of the CDE was 0.072 m/s (percentile-based bootstrap 95% CI - 0.292, 0.445). Results from PBA indicated that the greater the extent of misclassification, the more the CDE may be estimated with bias and over-optimistic precision. CONCLUSIONS: Our study provided supporting information on metformin's potential role as a repurposed medication to improve physical performance in nondiabetic older adult patients with physical prefrailty/frailty and probable sarcopenia. Unlike the main trial results, our results do not rule out the possibility of either a meaningful benefit or meaningful harm of metformin, provided that full adherence can be assured. We highlighted the parametric g-formula as a useful method in trials to target estimands with a hypothetical strategy to handle treatment non-adherence. TRIAL REGISTRATION: ISRCTN ISRCTN29932357.
Church-based problem-solving therapy for adolescent girls and young women with a history of gender-based violence in Zambia: study protocol for a hybrid type 1 randomized controlled trial.
Ahmed CV, Thornicroft M, Chileshe K … +7 more , Ntebeka BM, Dovel K, Bogart LM, Chávez NR, Bwalya FT, Brooks MJ, Swendeman D
Trials · 2026 Apr · PMID 41957660 · Full text
BACKGROUND: Adolescent girls and young women (AGYW) in sub-Saharan Africa face a disproportionate burden of gender-based violence (GBV), HIV risk, and mental health challenges. Despite the demonstrated effectiveness of p...
BACKGROUND: Adolescent girls and young women (AGYW) in sub-Saharan Africa face a disproportionate burden of gender-based violence (GBV), HIV risk, and mental health challenges. Despite the demonstrated effectiveness of psychological interventions such as problem-solving therapy (PST), there is limited evidence on culturally adapted models for GBV-exposed AGYW that concurrently address HIV and mental health, particularly in settings with constrained mental health infrastructure. OBJECTIVE: This study outlines the protocol for a randomized controlled trial evaluating Mpata Yathu, a church-based adaptation of the Friendship Bench intervention, which delivers lay counselor-led PST to AGYW with a history of GBV in Lusaka, Zambia. METHODS: A hybrid implementation-effectiveness type 1 randomized controlled trial (intervention and waitlist control arms) will be conducted among 90 AGYW, aged 15 to 24, per arm with moderate depressive symptoms, lifetime GBV exposure, and HIV risk or diagnosis. The intervention comprises six individual PST sessions delivered over 3 months in church spaces. Implementation outcomes (feasibility, acceptability, fidelity), common mental disorder (CMD) symptoms (primary outcome), and exploratory outcomes (depression, anxiety, PTSD, HIV engagement, GBV attitudes, childhood adversity, coping self-efficacy) will be assessed at baseline, 3, and 6 months. The trial is powered to detect changes in CMD symptoms only. Mixed-methods data will inform feasibility, intervention refinement, and hypotheses regarding mental health as a mediator of HIV outcomes. Process evaluations will use the Consolidated Framework for Implementation Research (CFIR). CONCLUSIONS: This trial will assess the potential of church-based PST to address the intersecting burdens of GBV, HIV, and mental health among AGYW in Zambia. Findings will offer insights into leveraging trusted community institutions (e.g., church and religious settings) for mental health and HIV care delivery in low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT07132905. Prospectively registered on August 13, 2025. CLINICALTRIALS: gov/study/NCT07132905.
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