Trials[JOURNAL]
Sun
200 papers
Treatment guided by cerebral oximetry monitoring in extremely preterm infants: a Bayesian analysis of the SafeBoosC-III randomised clinical trial.
Hansen ML, Olsen MH, Lange T … +7 more , Gluud C, Haugegaard T, Christensen R, Thabane L, Greisen G, Jakobsen JC, SafeBoosC-III Trial Group
Trials · 2026 Apr · PMID 42050627 · Full text
PURPOSE: The SafeBoosC-III trial compared treatment guided by cerebral oximetry monitoring for the first 72 h after birth with usual care in 1601 extremely preterm infants. Incidence of death or severe brain injury at 36...
PURPOSE: The SafeBoosC-III trial compared treatment guided by cerebral oximetry monitoring for the first 72 h after birth with usual care in 1601 extremely preterm infants. Incidence of death or severe brain injury at 36 weeks of postmenstrual age did not differ between the cerebral oximetry and usual care group (relative risk with cerebral oximetry, 1.03; 95% CI 0.90 to 1.18). To assess the probability of clinically important benefit or harm, we conducted secondary analyses in a Bayesian framework. METHODS: Primary analyses used a weakly informative prior assuming a wide range of effects, to assess the probability that treatment guided by cerebral oximetry monitoring carried an a priori defined clinically important benefit or harm (a relative risk below 0.90 or above 1.10) or any benefit or harm (a relative risk differing from 1.0) for death or severe brain injury. Secondary analyses used an evidence-based prior derived from relevant prior trials. RESULTS: Posterior probabilities of clinically important benefit or harm were 1.5% and 19.2%, respectively. Posterior probabilities of any benefit or harm were 28.7% and 71.3%, respectively. Probabilities derived from secondary analyses using evidence-based priors were consistent with those from the primary analysis. CONCLUSION: Treatment guided by cerebral oximetry monitoring during the first 72 h after birth in extremely preterm infants resulted in posterior probabilities of 1.5% for a clinically important benefit and 19.2% for a clinically important harm with respect to the incidence of death or severe brain injury at 36 weeks of postmenstrual age. TRIAL REGISTRATION: ClinicalTrials.gov NCT03770741. Registered on 12 July 2018.
Comparison of anesthesia efficacy between subclavius muscle plane block and interscalene brachial plexus block for open reduction and internal fixation of clavicle fractures: study protocol for a randomized non-inferiority clinical trial.
Li CG, Yuan W, Wei J … +5 more , Mou CY, Guo J, Zhong F, Fan K, Gong WY
Trials · 2026 Apr · PMID 42050621 · Full text
BACKGROUND: Interscalene brachial plexus block (ISBPB) combined with supraclavicular nerve block or superficial cervical plexus block has been reported to be a reliable, efficacious anesthesia technique for clavicle frac...
BACKGROUND: Interscalene brachial plexus block (ISBPB) combined with supraclavicular nerve block or superficial cervical plexus block has been reported to be a reliable, efficacious anesthesia technique for clavicle fracture surgery. However, several serious adverse events impeded the development of this technique. Herein, we propose a novel nerve block technique-the subclavius muscle plane block (SMPB) combined with supraclavicular nerve block-that selectively targets the sensory nerves innervating the surgical region of the clavicle. We hypothesize that SMPB may achieve non-inferior anesthesia efficacy for clavicle surgery compared to ISBPB when combined with supraclavicular nerve block, with fewer complications. METHODS: This study is a prospective, single-center, randomized, controlled, non-inferiority trial. A total of 76 patients scheduled for open reduction and internal fixation of clavicle fractures will be divided into two groups at random to receive either SMPB or ISBPB, combined with supraclavicular nerve block. The primary outcome will be to compare the proportion of patients not requiring sufentanil supplementation intraoperatively between the two groups. The secondary outcomes will include the pulmonary function before and 30 min after the block, onset time of anesthesia, block-related complications, conversion rate to general anesthesia, intraoperative sufentanil supplementation, surgery duration, intraoperative hemodynamic adverse events, first onset time of pain, first time to patient-controlled bolus, postoperative sufentanil consumption, Numerical Rating Scale scores for rest and dynamic pain at 3, 6, 12, and 24 h postoperatively, motor block grade at 3, 6, 12, and 24 h postoperatively, postoperative nausea and vomiting, metoclopramide dose, nerve injury, patient satisfaction score, and surgeon satisfaction score. DISCUSSION: This study explores the SMPB as a novel anesthetic technique for clavicle surgery. Compared to ISBPB, SMPB may offer effective anesthesia while reducing complications regarding limb immobility and phrenic nerve paralysis, thus potentially enhancing patient safety, comfort, and postoperative recovery. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2500096952. Registered on February 10, 2025.
Digital tools for recruitment and retention of participants in paediatric clinical research: a scoping review.
Tan E, Loveys K, Ali W … +2 more , McKinlay CJD, Dalziel SR
Trials · 2026 Apr · PMID 42050591 · Full text
BACKGROUND: Digital tools are increasingly used to support recruitment and retention of participants in paediatric research, particularly since the COVID-19 pandemic. However, the extent of the evidence supporting this m...
BACKGROUND: Digital tools are increasingly used to support recruitment and retention of participants in paediatric research, particularly since the COVID-19 pandemic. However, the extent of the evidence supporting this method in paediatric populations has yet to be evaluated. This scoping review aimed to review the literature on digital tools for recruitment and/or retention of participants in paediatric research, including emerging evidence following the pandemic. METHODS: A scoping review was conducted following Joanna Briggs Institute methodology. We included peer-reviewed quantitative, qualitative, and mixed-method studies evaluating a digital tool for recruitment or retention in paediatric research in any patient population aged <13 years. Records were identified from systematic database searches with a librarian (EMBASE, MEDLINE, CINAHL), limited to English, from 2013 onwards (last search 03/07/2024), and manual searches. Records were screened and extracted independently in duplicate. The data were charted and narratively summarised. RESULTS: Sixty-one out of 4988 records were included. Most evaluations used an observational design; only 5 (8%) involved a randomised experiment. The host studies were mostly aiming to recruit children aged 5-12 years (n = 42; 69%), with a predominantly health promotion (n = 18; 30%), developmental (n = 12; 20%), or oncology (n = 9; 15%) focus. Most studies used multi-component digital interventions for recruitment (n = 39/53; 74%) or retention (n = 17/31; 55%). Social media (n = 33/52; 62%) and websites (n = 19/53; 36%) were most commonly used for recruitment, whereas text/instant messaging (n = 17/31; 55%) and email (n = 11/31; 36%) were the most common retention strategies. The estimates of recruitment and retention rates, and reach per digital tool varied widely between studies. Strategies in underserved populations reflected those used most commonly overall. Multi-component digital strategies were found to support a high rate of retention (84.1-90.7%) during pandemic restrictions. CONCLUSIONS: This scoping review highlights the broad array of digital tools that have been used to support recruitment and retention in studies of infants and children, including in subgroups of underserved populations and in response to the COVID-19 pandemic. Most evaluations were observational and examined multi-component digital interventions. The lack of studies with a robust analytical design in the literature signals a need for further high-quality, randomised, within-study evaluations following standardised reporting criteria. REGISTRATION: The protocol was registered on the Open Science Framework (OSF) at https://osf.io/ybfhr/ . Registered on July 5 2024.
Optimizing metabolic management on integrase-based ART (OPTIMAR): study protocol for a 2 × 2 factorial, randomised, double-blind placebo-controlled trial to compare the addition of dapagliflozin versus placebo, and rosuvastatin plus ezetimibe versus pitavastatin, in people with HIV on integrase strand transfer inhibitor-based antiretroviral therapy with elevated metabolic risk.
Nyein PP, Haskelberg H, Martinello M … +18 more , Lowe M, Goodman-Meza D, Avihingsanon A, Kelleher AD, Rodgers A, Schutte AE, Nnakelu EC, Byakwaga H, Trevillyan J, Losso M, Kumarasamy N, Azwa RISR, Kaplan R, Clifton B, Arnott C, Dharan NJ, Petoumenos K, Matthews GV
Trials · 2026 Apr · PMID 42050587 · Full text
BACKGROUND: People with HIV have an increased cardiovascular disease (CVD) risk due to both HIV and adverse effects of treatments. The currently preferred class of anti-retroviral drugs, integrase strand transfer inhibit...
BACKGROUND: People with HIV have an increased cardiovascular disease (CVD) risk due to both HIV and adverse effects of treatments. The currently preferred class of anti-retroviral drugs, integrase strand transfer inhibitors (INSTIs), has variably been linked to higher CVD risk and weight gain. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce CVD events and heart failure hospitalisations in people with or without type 2 diabetes, while also reducing weight and blood pressure, but have not been studied in people with HIV. Pitavastatin lowers CVD events in those with HIV, although it is not widely available. METHODS: OPTIMAR is a 2 × 2 factorial, randomised, placebo-controlled, double-blind, phase III/IV trial and will examine the efficacy and safety of dapagliflozin 10 mg versus placebo on metabolic parameters and of rosuvastatin 10 mg + ezetimibe 10 mg versus pitavastatin 4 mg. A cardiac substudy will determine the effect of dapagliflozin versus placebo on epicardial adipose tissue (EAT) volume and coronary plaque characteristics. Virologically suppressed individuals with HIV on INSTI-based ART aged 40-75 years who had a significant weight gain after starting INSTI or BMI ≥ 30 kg/m will be included. Participants will be randomised 1:1 to blinded dapagliflozin or placebo, followed by 1:1 to open-label rosuvastatin + ezetimibe or pitavastatin for 48 weeks. The primary endpoints will be body weight and LDL reduction for the SGLT2i and statin randomisations respectively in the modified intention-to-treat population. Follow-up will continue to 48 weeks with primary analysis at week-24 and follow-up analysis at week-48. DISCUSSION: OPTIMAR is the first trial to investigate the use of SGLT2i as a cardiometabolic intervention in people with HIV. Demonstrating favourable cardiometabolic effects of SGLT2i will introduce an innovative approach to primary CVD prevention in this at-risk population and support conducting larger trials evaluating clinical endpoints including major adverse cardiovascular events. If the combination of rosuvastatin and ezetimibe is found to be similar or superior to pitavastatin, this will inform a more feasible lipid management approach for people with HIV internationally, especially in resource-limited settings. The cardiac sub-study will further clarify the cardioprotective role of SGLT2i and provide mechanistic insights. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06317051 ( https://clinicaltrials.gov/study/NCT06317051?cond=HIV&intr=Dapagliflozin&aggFilters=status:not%20rec&rank=2 ). Registration on 21 February 2024.
Effects of tDCS on brain function in patients with post-stroke cognitive impairment: a randomised controlled study protocol based on TMS and fNIRS.
Zhu Y, Duan H, Zhang Q … +6 more , Li P, Jiang L, Bao Y, Li W, Zhuang M, Liu X
Trials · 2026 Apr · PMID 42046090 · Full text
BACKGROUND: Transcranial direct current stimulation (tDCS) positively affects post-stroke cognitive impairment (PSCI). However, the optimal stimulation protocol remains unclear, possibly because of the lack of objective...
BACKGROUND: Transcranial direct current stimulation (tDCS) positively affects post-stroke cognitive impairment (PSCI). However, the optimal stimulation protocol remains unclear, possibly because of the lack of objective assessment methods. Therefore, this study aims to investigate the impact of tDCS on the modulation of the excitation/inhibition (E/I) balance and its effects on brain function in patients with PSCI using transcranial magnetic stimulation (TMS) and functional near-infrared spectroscopy (fNIRS). METHODS: This study is a single-centre, two-armed randomised controlled trial. A total of 40 patients with PSCI will be recruited and randomly assigned to real and sham tDCS groups in a 1:1 ratio. Both groups will receive either real or sham tDCS in addition to conventional treatment. In both groups, electrodes will be placed at the same positions, with the anode and cathode above the left and right dorsolateral prefrontal cortex, respectively. The real tDCS group will receive continuous current throughout the session, whereas the sham tDCS group will receive current generation for only the first 30 s. The treatment will consist of a 3-week intervention with one session per day, five sessions per week and 30 min per session. A 4-week follow-up will be conducted at the end of the treatment. The primary outcome is the change in Montreal cognitive assessment (MoCA) scores from baseline (T0) to immediately post-intervention (T1). Secondary outcomes include Barthel index, levels of intracortical inhibition measured by TMS and cortical activation and interhemispheric connectivity assessed by fNIRS during a Stroop task. DISCUSSION: This study will combine TMS and fNIRS to explore the effects of tDCS on the modulation of the E/I balance and its impact on blood oxygen levels and neural activity. Our results are expected to provide a clinical reference for the development of more precise tDCS protocols. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2300077453. Registered on November 9, 2023.
Labelling of subpleural pulmonary nodules with blue dye and contrast agents under CT-guided control and subsequent video-assisted thoracoscopic resection: the BLUEPAT prospective randomised study.
Chovanec Z, Červeňák V, Čundrle I … +6 more , Šitina M, Vaníček J, Berková A, Hanslík T, Penka I, Součková L
Trials · 2026 Apr · PMID 42045970 · Full text
BACKGROUND: Colour marking of indicated nodules is an innovative, accurate, and gentle method that allows subsequent wedge resection of the marked tissue using a mini-invasive, video-assisted thoracoscopic (VATS) method...
BACKGROUND: Colour marking of indicated nodules is an innovative, accurate, and gentle method that allows subsequent wedge resection of the marked tissue using a mini-invasive, video-assisted thoracoscopic (VATS) method with all its benefits. One of the expected benefits of this clinical trial is introducing and optimising the evaluated way into routine management in diagnosing and treating focal lung diseases. The BLUEPAT clinical trial aims to assess the technique of colour marking of subpleural deposited small lung nodules with the subsequent performance of VATS wedge resection in surgical practice. METHODS: The BLUEPAT clinical trial is a prospective, monocentric, open-label, randomised study that will include 72 participants with subpleural deposited nodules with the need for additional histological diagnostics to optimise subsequent treatment. These patients will be randomised into two arms in a 1:1 ratio. The interventional arm will undergo VATS wedge resection of lung nodules marked with Patent Blue V and contrast agent iohexol under CT-guided control. The control arm will undergo VATS resection without prior colour coding of the lung nodules. The feasibility and safety of both methods will be assessed based on the evaluation of the parameters of the primary and secondary objectives of the study. The safety of the methods will be monitored by recording all related adverse events. All enrolled patients will undergo a 30-day follow-up period within the framework of clinical trial. RESULTS: This article reports the clinical trial protocol; outcome data will be published upon study completion. DISCUSSION: The BLUEPAT clinical trial offers a novel assessment of this innovative approach for the diagnosis and treatment of focal lung diseases. The use of patent blue dye has been well established in diagnostic procedures for breast cancer and this study extends its potential application to pulmonary indications. TRIAL REGISTRATION: EudraCT Number 2021-001122-22. Registered on March 18, 2021.
Efficacy and safety of fecal microbiota transplantation in reducing recurrence of colorectal adenomas after endoscopic resection: study protocol for a multicenter, open-label, randomized, no-treatment-controlled trial.
Huang J, Chen Z, Wang M … +3 more , Yang C, Wang A, Chen Y
Trials · 2026 Apr · PMID 42045958 · Full text
BACKGROUND: Endoscopic resection is the standard treatment for colorectal adenoma (CRA), a key precursor to colorectal cancer (CRC). However, a high rate of recurrence post-procedure poses a significant challenge for lon...
BACKGROUND: Endoscopic resection is the standard treatment for colorectal adenoma (CRA), a key precursor to colorectal cancer (CRC). However, a high rate of recurrence post-procedure poses a significant challenge for long-term CRC prevention. Growing evidence suggests gut microbial dysbiosis contributes to adenoma development and recurrence. This trial will test the hypothesis that restoring a healthy gut microbiome with fecal microbiota transplantation (FMT) can reduce the recurrence of CRA after endoscopic resection. METHODS: This protocol describes a multicenter, open-label, randomized, no-treatment-controlled trial that will enroll 466 participants with CRA following endoscopic resection. Participants will be randomly assigned in a 1:1 ratio to receive either FMT or no treatment (control). The FMT intervention consists of an initial colonoscopic infusion and oral capsules, followed by oral maintenance capsules at months 3, 6, and 9. The primary outcome is the rate of CRA recurrence at the 12-month follow-up colonoscopy. Key secondary outcomes include the incidence of all polypoid lesions, changes in the gut and mucosal microbiota composition, the incidence of CRC, and a comprehensive assessment of adverse events to evaluate safety. DISCUSSION: This trial is designed to provide high-quality evidence on the efficacy and safety of FMT for preventing CRA recurrence. The findings may support a novel, microbiome-based strategy for the secondary prevention of CRC and provide mechanistic insights into the role of the gut microbiota in colorectal carcinogenesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT06205862. Registered on 16 January, 2024. https://clinicaltrials.gov/study/NCT06205862 .
Enhancing the scope of the Trials to Publications tool by identifying ClinicalTrial.gov registry mentions in full-text.
Holt AW, Smalheiser NR
Trials · 2026 Apr · PMID 42035165 · Full text
We have previously described a free, public web-based tool, Trials to Publications, https://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/TrialPubLinking/trial_pub_link_start.cgi , which employs a machine-learning mode...
We have previously described a free, public web-based tool, Trials to Publications, https://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/TrialPubLinking/trial_pub_link_start.cgi , which employs a machine-learning model based on title, abstract, and other metadata features to predict which publications are likely to present clinical outcome results from a given registered trial in ClinicalTrials.gov. We have now updated and expanded the scope of the tool, by extracting mentions of ClinicalTrials.gov registry numbers (NCT numbers) from the full-text of 3 online biomedical article collections (open access PubMed Central (PMC), EuroPMC, and OpenAlex), as well as retrieving biomedical publications that are mentioned within the ClinicalTrials.gov registry itself. These mentions greatly increase the number of linked publications identified by the tool and should assist those carrying out evidence syntheses as well as those studying the metascience of clinical trials.
Effect of constraint standing training on balance and gait in hemiparetic stroke patients: a single-blind randomized controlled trial protocol.
Zhou L, Chu H, Cao M … +3 more , Rahim NAA, Yusof HA, Hou Y
Trials · 2026 Apr · PMID 42035149 · Full text
BACKGROUND: Modified Constraint-Induced Movement Therapy (mCIMT) has demonstrated significant potential in rehabilitating lower extremity motor impairments following stroke. However, mCIMT's application is often limited...
BACKGROUND: Modified Constraint-Induced Movement Therapy (mCIMT) has demonstrated significant potential in rehabilitating lower extremity motor impairments following stroke. However, mCIMT's application is often limited by the need for specialized devices to constrain the non-affected extremity and longer training duration. Constraint Standing Training (CST) is a novel variation of mCIMT that addresses these limitations by eliminating the need for constraining devices and reducing training time, thereby enhancing its feasibility for clinical implementation. Despite these advantages, the specific effects of CST on balance and gait in stroke patients remain underexplored. METHODS: This study will use a randomized, controlled, single-blinded design. Fifty stroke patients in the chronic phase, with gait disabilities and the ability to stand independently, will be randomly assigned to either the CST group or a control group using a computer-generated randomization sequence. Exclusion criteria include physiological or cognitive impairments that may hinder evaluation or training. Both groups will undergo daily 1-h training sessions, five times per week, for 8 weeks. The CST group will undergo sequential standing training using shaping strategies from a single plane to multiple planes, while the control group will receive conventional intensive training, which includes balance and gait exercises commonly used in clinical practice. Assessments will be carried out at baseline (T), mid-intervention (T), post-intervention (T), and 1 month follow-up (T). The primary outcome of this trial is the Timed Up and Go (TUG) test. Secondary outcomes include the 10-Meter Walk Test, 6-Minute Walk Test, Berg Balance Scale, three-dimensional gait analysis, and surface electromyography. Missing data will be handled using multiple imputation by chained equations. Data will be analyzed using two-way repeated measures ANOVA or generalized estimating equations to determine differences and identify clinically relevant changes. DISCUSSION: This protocol provides detailed CST methods to guide future research and clinical application. The study employs a randomized controlled trial design to robustly evaluate CST's effects on balance and gait in hemiparetic stroke patients. CST's sequential, multi-plane exercises offer a potentially practical alternative. However, larger, multi-center trials are recommended for future validation. TRIAL REGISTRATION: This trial is registered at www.chictr.org.cn . REGISTRATION NUMBER: ChiCTR2400086282. Date of registration: 27 June 2024.
Evaluating fitness-for-use of electronic health records in ascertaining baseline characteristics and clinical outcomes in clinical trials: insights from the VESALIUS EHR demonstration project.
Gouda P, Nelson AJ, Raman SR … +8 more , Qualls LG, Hammill BG, Garg J, Benziger CP, Divakaran R, Nilles EK, Marsolo K, O'Brien EC
Trials · 2026 Apr · PMID 42032789 · Full text
INTRODUCTION: A tremendous amount of clinical data is collected and stored in electronic health records (EHRs). Whether this data can be harnessed at scale to facilitate clinical trial conduct remains to be seen. METHODS...
INTRODUCTION: A tremendous amount of clinical data is collected and stored in electronic health records (EHRs). Whether this data can be harnessed at scale to facilitate clinical trial conduct remains to be seen. METHODS: The Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV) trial included an embedded study evaluating the fitness-for-use of EHR data to ascertain baseline demographics (age, sex, race/ethnicity, history of coronary disease, cerebrovascular disease, peripheral artery disease, heart failure, diabetes, hypertension, and atrial fibrillation), laboratory (creatinine, lipid values), and outcomes (myocardial infarction, stroke, revascularization, and heart failure) data, compared to trial data collected through a study case report form (CRF). These are described using concordance statistics (overall agreement, sensitivity, specificity, negative predictive value, positive predictive value, kappa statistic and bias). RESULTS: The VESALIUS-CV EHR substudy included 75 participants (9 sites). For categorical baseline variables, the overall agreement between EHR and CRF data ranged between 81.3 and 98.7%, sensitivity ranged between 42.9 and 100%, specificity ranged between 50.0 and 100%, and kappa statistic ranged between 0.2 and 0.8. Identification of a history of peripheral artery disease in EHR data was poor (positive predictive value 23.1%). Of 431 continuous variables, bias was generally low but was associated with moderate imprecision, with exact matches observed in 95.8% of cases. Of a total of 20 outcome events, the overall agreement ranged between 86.7 and 100%, sensitivity ranged between 50 and 100%, specificity ranged between 86.7 and 100%, and kappa statistic ranged between 0.7 and 1.0. CONCLUSION: EHR data has the potential to facilitate and reduce the burden of data collection for clinical trials, but further work is required to optimize data extraction and improve accuracy.
PRIMA: randomized prospective multicenter non-inferiority study for primary diagnosis of clinically significant PRostate cancer by PSA and MR IMAging-study protocol for a randomized diagnostic accuracy trial.
Al-Monajjed R, Albers P, Boschheidgen M … +7 more , Radtke JP, Droop J, Benner A, Hadaschik B, Antoch G, Schimmöller L, PRIMA Study Group
Trials · 2026 Apr · PMID 42032761 · Full text
BACKGROUND: Diagnostic pathways based on PSA, digital rectal examination (DRE), and systematic biopsy (SB) may miss clinically significant prostate cancer (csPCa) and lead to overdiagnosis of indolent disease. Multiparam...
BACKGROUND: Diagnostic pathways based on PSA, digital rectal examination (DRE), and systematic biopsy (SB) may miss clinically significant prostate cancer (csPCa) and lead to overdiagnosis of indolent disease. Multiparametric MRI (mpMRI) and MRI-targeted biopsy (TB) improve detection of csPCa; however, the additional diagnostic value of routine SB in biopsy-naïve men with suspicious MRI findings remains controversial. METHODS: PRIMA is a randomized, prospective, multicenter non-inferiority diagnostic accuracy trial in eight German hospitals. Biopsy-naïve men aged 50-75 years with PSA ≥ 3 ng/ml and/or suspicious DRE undergo mpMRI (PI-RADS v2.1, PI-QUAL v2). Men with PI-RADS 4-5 or PI-RADS 3 with PSA density > 0.15 are randomized 1:1 to TB only (Arm A) or TB + SB (Arm B). Persistent PI-RADS 4-5 lesions with negative biopsy undergo MRI in-bore biopsy. OUTCOMES: Co-primary endpoints are csPCa (ISUP ≥ 2) detection and detection of clinically insignificant cancer (ISUP 1). Secondary endpoints include patient-reported outcomes (EORTC-QLQ-C30, EPIC-26, VAS), biopsy-related complications, biopsy approach, MRI in-bore yield, AI/radiomics validation and follow-up cancer incidence. SAMPLE SIZE: One thousand nine hundred eight men were allocated to achieve 1590 analyzable patients (> 80% power; non-inferiority margin δ = 13%). DISCUSSION: PRIMA will provide high-level evidence whether systematic biopsy can be safely omitted in MRI-positive biopsy-naïve men, potentially reducing diagnostic morbidity and overtreatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04993508. Registered on 2 December 2022.
Serious game-interactive digitalised cognitive behavioural therapy versus psychoeducation for adults with mild to moderate depression: study protocol for a randomised, parallel-group, controlled trial.
Yang J, Chang S, Zhang Y … +7 more , Cheng S, Zhao J, Li N, Cai L, Xian C, Wang X, Wang G
Trials · 2026 Apr · PMID 42032743 · Full text
BACKGROUND: Serious game-interactive digital cognitive behavioural therapy (dCBT) has emerged as an innovative approach to managing depression, combining the efficacy of CBT with gamified and interactive elements to enha...
BACKGROUND: Serious game-interactive digital cognitive behavioural therapy (dCBT) has emerged as an innovative approach to managing depression, combining the efficacy of CBT with gamified and interactive elements to enhance user engagement and adherence. This protocol outlines the structure and methodology of a randomised controlled trial (RCT) designed to evaluate the effectiveness of serious game-interactive dCBT in alleviating depressive symptoms, compared to psychoeducation. METHODS: This study is a parallel-group superiority RCT to assess the efficacy of the serious game-interactive dCBT. In total, 124 patients aged 18 to 45 years with mild to moderate major depression were recruited primarily from the community, with a smaller portion from the outpatient department of Beijing Anding Hospital, and were included in two groups. Randomisation was performed using computer-generated random allocation sequences concealed within sealed envelopes. The intervention duration is 6 weeks. Assessments, conducted using a combination of self-rated and observer-rated scales, are scheduled at baseline, week 2, week 4, and week 6. The primary outcome is improvement in depressive symptoms at week 6, measured by the reduction in Beck Depression Inventory (BDI) scores. Secondary outcomes assessed at week 6 include changes in automatic thoughts, pleasure responsiveness, and quality of life. Self-rated outcomes are collected every 2 weeks to investigate the process of change. As the revision was submitted, participant recruitment has been completed. DISCUSSION: This is the first RCT of serious game-interactive dCBT conducted in China. The interactive design overcomes the limitations of computerised CBT, while the fully digital traceability model addresses the issue of CBT treatment adherence. Additionally, the modular architecture facilitates the scalability of applications. Given its accessibility and cost-effectiveness, serious game-interactive dCBT may pave new pathways for depression treatment. TRIAL REGISTRATION: ChiCTR2400085819.
Gonadotropin-releasing hormone agonist (GnRH-a) pretreatment duration and letrozole supplementation for optimizing live birth rates in women with adenomyosis undergoing frozen-thawed embryo transfer (GOLD-FET): study protocol for a multicenter, 2 × 2 factorial randomized controlled trial in China.
Xiong Y, Gu F, Du L … +7 more , Gu J, Ke Z, Xu Y, Mol BW, Zheng B, Lin X, Xu Y
Trials · 2026 Apr · PMID 42032741 · Full text
BACKGROUND: Adenomyosis, an estrogen-dependent condition characterized by endometrial invasion into the myometrium, is associated with reduced live birth rates and increased miscarriage risk in women undergoing assisted...
BACKGROUND: Adenomyosis, an estrogen-dependent condition characterized by endometrial invasion into the myometrium, is associated with reduced live birth rates and increased miscarriage risk in women undergoing assisted reproductive technologies (ART). Gonadotropin-releasing hormone agonists (GnRH-a) are commonly used for pretreatment before frozen-thawed embryo transfer (FET) in adenomyosis patients, but optimal duration remains unclear. Letrozole, an aromatase inhibitor, may enhance GnRH-a efficacy by mitigating its flare-up effect and reducing peripheral estrogen production, yet high-level evidence on their combined effect is lacking. This study aims to compare the live birth rate and other pregnancy outcomes between one and two doses of GnRH-a pretreatment with or without letrozole supplementation in women with adenomyosis undergoing FET. METHODS: This is a 2 × 2 factorial, multi-center, open-label, randomized controlled trial (RCT) conducted at three reproductive medical centers in China, with a planned enrollment of 432 women aged 20-38 years with sonographically diagnosed adenomyosis scheduled for single blastocyst FET. This study is designed as a superiority trial. Recruitment will be conducted by trained clinical research coordinators. Participants are randomized in a 1:1:1:1 ratio to four arms: one dose of GnRH-a (3.75 mg), two doses of GnRH-a, one dose of GnRH-a with letrozole (2.5 mg daily for 28 days), or two doses of GnRH-a with letrozole (2.5 mg daily for 28 days). The primary outcome is live birth rate. Secondary outcomes include fertility outcomes, pregnancy and obstetric outcomes, and neonatal outcomes. Safety outcomes, including the incidence and severity of low-estrogen-related adverse events (e.g., hot flashes, bone loss, vaginal dryness) and other serious adverse events, will be collected and compared. An internal pilot phase will assess procedural feasibility when approximately 25 participants are randomized per arm. Data are collected via medical records and follow-up assessments up to 6 months postpartum. DISCUSSION: This factorial RCT is the first to assess the synergistic effects of GnRH-a dosage and letrozole supplementation, overcoming limitations of single-factor studies. By comprehensively evaluating pregnancy outcomes, the study aims to optimize pretreatment strategies, inform clinical guidelines, and improve pregnancy outcomes for adenomyosis patients undergoing FET. TRIAL REGISTRATION: ClinicalTrials.gov NCT07065539. Registered on 14 July 2025. https://clinicaltrials.gov/study/NCT07065539 . The first participant was enrolled in August 2025.
Platform for the Evaluation of innovations in Radiation oncology through registry-based conduct of multi-centric pragmatic randomized trials: PERa implementation.
Giguère P, Bahig H, Westra S … +11 more , Roberge D, Bourque JM, Masucci GL, Nkurunziza ES, Freire V, Belliveau C, Duplan D, Vigneault E, Wong P, Lang P, Ménard C
Trials · 2026 Apr · PMID 42032732 · Full text
PURPOSE: Radiotherapy has achieved substantial progress often attributed to accelerated technological innovation over decades. However, randomized controlled trials (RCTs) are costly, difficult to fund and to conduct, su...
PURPOSE: Radiotherapy has achieved substantial progress often attributed to accelerated technological innovation over decades. However, randomized controlled trials (RCTs) are costly, difficult to fund and to conduct, such that the generation of quality evidence is outpaced by changes in practice. We sought to evaluate the implementation performance of a platform approach to the conduct of pragmatic RCTs in radiation oncology. METHODS: We implemented PERa, a platform consisting of a prospective registry of patients receiving standard-of-care radiation therapy, designed to support pragmatic registry-based RCT (rRCT) methods and staged informed consent. Implementation performance metrics included rate of registry enrollment, acceptability of re-contact and/or serving as controls for interventional trials, activation and recruitment of embedded comparative effectiveness rRCTs, compliance to study arms, and completeness of ePRO data acquired at scale. RESULTS: Between January 1, 2018 and December 31, 2023, the registry accrued 1415 participants across 5 participating institutions. At time of stage 1 consent, 93% agreed to re-contact for participation in a clinical trial, and 97% consented to serve as control. Seven embedded rRCTs were activated, and one third of participants (n = 477) were randomized. Only two study arm non-compliance events were recorded. Although 97% of subjects consented to ePROs, completion rate was only 53% in those with stage 1 only consent, rising to 62% in those subjects also consented at a second stage to a companion rRCT. CONCLUSION: The PERa platform is met with high acceptance demonstrating efficient conduct of rRCTs embedded in routine radiation oncology practice. Future work to improve ePRO completions and automate harmonization with EMR data lakes have the potential to improve the quality of evidence generation and support learning health systems. TRIAL REGISTRATION: NCT03378856: Registered on December 12, 2017. NCT04100174: Registered on September 20, 2019. NCT04178174: Registered on November 17, 2019. NCT05457699: Registered on July 04, 2022. NCT04405401: Registered on May 24, 2020. NCT04901234: Registered on May 17, 2021. NCT05317026: Registered on March 08, 2022.
Challenges and strategies to improve recruitment in international, multi-centre research studies in locally recurrent rectal cancer: experience from the Locally Recurrent Rectal Cancer-Quality of Life (LRRC-QoL) study.
McKigney N, Croft J, Velikova G … +2 more , Brown JM, Harji DP
Trials · 2026 Apr · PMID 42032664 · Full text
BACKGROUND: Locally recurrent rectal cancer (LRRC) is an emerging area for research; however, it represents significant challenges as a relatively rare form of advanced pelvic malignancy, from both a recruitment and stud...
BACKGROUND: Locally recurrent rectal cancer (LRRC) is an emerging area for research; however, it represents significant challenges as a relatively rare form of advanced pelvic malignancy, from both a recruitment and study setup and delivery perspective. To date, there have been relatively few published trials in this setting. High-quality, multi-centre, prospective studies could offer helpful insights regarding the challenges associated with delivering studies in rare disease settings such as LRRC, and how to effectively address them. METHODS: The Locally Recurrent Rectal Cancer-Quality of Life (LRRC-QoL) study is an international, multi-centre, mixed-methods study of health-related quality of life (HrQoL) in LRRC. The International Surgical Trials Toolkit was utilised as a guideline in navigating site setup processes and to describe the challenges encountered during this study. A modified Quintet Recruitment Intervention (QRI) was used as a framework to identify recruitment challenges and drive improvements. RESULTS: Overall, 227 patients were recruited to the LRRC-QoL study across 14 countries. Significant challenges were encountered during site setup, including issues related to legal agreements which were further complicated by Brexit, expenses related to translation, and requirements for multiple ethical approvals. Delays during study setup and recruitment challenges occurred due to the COVID-19 pandemic. Several strategies were identified through the modified QRI with a positive impact on recruitment. Recruitment pathways were refined to a more streamlined, centralised approach, facilitated by verbal consent to contact. Recruitment rates also improved with the introduction of multiple options for participation, including traditional paper-based methods, online, and via telephone. Patient information leaflets were refined following patient and public involvement (PPI) work. CONCLUSIONS: Several approaches identified during the LRRC-QoL study should be considered in the development of future studies and trials recruiting patients with LRRC. These include undertaking PPI during study development, identifying flexible recruitment strategies which complement sites' existing clinical processes, and partnering with existing collaborative networks. Study registration The LRRC-QoL study registration reference: ISRCTN13692671 ( https://doi.org/10.1186/ISRCTN13692671 ).
The use of Bayesian methods for the analysis of Studies Within A Trial: a proof-of-concept case study.
Cro S, He Z, Babalis D … +1 more , Billot L
Trials · 2026 Apr · PMID 42032615 · Full text
UNLABELLED: BACKGROUND AND AIMS: A Study Within A Trial (SWAT) is a research study embedded within a larger trial which aims to investigate different strategies for a particular trial process, such as trial recruitment....
UNLABELLED: BACKGROUND AND AIMS: A Study Within A Trial (SWAT) is a research study embedded within a larger trial which aims to investigate different strategies for a particular trial process, such as trial recruitment. It is imperative such studies, which are often underpowered, employ efficient and informative analytical methods. The use of Bayesian methods and interpretation of SWAT results in this context requires exploration. Bayesian methods provide direct probability statements about intervention effects and readily enable ACceptability Curve Estimation using Probability above Threshold (ACCEPT) analyses, which consider the probability of the tested intervention being effective for different threshold values. Additionally, they provide an opportunity to incorporate the results of previous similar studies within the analysis using informative priors. This proof-of-concept study re-analysed two previous SWATs using Bayesian methods and ACCEPT analyses. METHODS: A SWAT conducted by Du et al. in 2009 and a subsequent SWAT by Mattock et al. in 2020 compared a video intervention against standard patient information on trial recruitment. For each SWAT, a primary Bayesian analysis was performed using a logistic model with non-informative priors. Sensitivity analysis explored informative priors informed by meta-analysis of previous similar studies; this included an analysis of the Mattock et al. SWAT incorporating the result of the earlier Du et al. SWAT. ACCEPT curves were constructed. Results were compared with frequentist analyses. RESULTS: For the Du et al. SWAT, the primary Bayesian analysis gave an OR for recruitment for the video relative to standard information of 2.12, 95% CrI: 0.38-4.65 and a posterior probability of the video being effective (OR > 1) of 0.86. When taking into account results of previous SWATs by using an informative prior there remained a moderately high probability of video benefit (0.82). For the latter Mattock et al. SWAT, the primary Bayesian analysis gave an OR for recruitment for the video relative to standard information of 0.26, 95% CrI: 0.07-0.51 and the posterior probability of the video being effective was 0.0005, indicating very little chance of effectiveness; ACCEPT plots facilitated interpretation by showing the probability that the video was better than standard information for OR > 0.8 was very small (0.0032). When taking into account the results of previous SWATs using an informative prior, including Du et al., the probability of the video being effective was still very small (0.12). CONCLUSIONS: Bayesian methods and ACCEPT analyses offer solutions to challenges experienced in the analysis and interpretation of SWATs, which are often underpowered. Greater use of these analytical approaches within SWATs will lead to a more accessible, improved evidence base on how to effectively conduct trials.
Efficacy of oral azithromycin in pregnant women living in low-middle income neighborhoods with high risk of reproductive tract infections to prevent preterm birth: study protocol of an individually randomized trial (pPAZI trial).
Sinha B, Biswas R, Dhabhai N … +12 more , Nangia S, Goyal N, Yadav R, More D, Banerjee D, Farooqui S, Puri M, Natchu UCM, Dang A, Chatterjee L, Rongsen-Chandola T, pPAZI trial group
Trials · 2026 Apr · PMID 42032611 · Full text
BACKGROUND: India contributes to around one-fifth of all preterm births globally. Reproductive tract infections (RTIs), colonization of fetal membranes, and associated maternal inflammatory immune response are recognized...
BACKGROUND: India contributes to around one-fifth of all preterm births globally. Reproductive tract infections (RTIs), colonization of fetal membranes, and associated maternal inflammatory immune response are recognized as a major trigger associated with preterm birth. Azithromycin is a broad-spectrum macrolide antibiotic with anti-inflammatory properties and is commonly used for symptomatic reproductive tract infections. Evidence from African trials suggests that oral azithromycin in the antenatal period can substantially reduce preterm births in malaria holoendemic settings (where all pregnant women receive antimalarials as standard). It is unclear whether the intervention works in South Asian settings where malaria is not holoendemic. METHODS: Using an individually randomized trial design, our primary study objective is to evaluate whether two doses of oral azithromycin (each dose 1 g/day for two consecutive days) compared to control (calcium 500 g/day for two consecutive days) during the antenatal period, i.e., at 20-24 weeks and at 28-32 weeks of gestation, in Indian women with high risk of reproductive tract infections can substantially prevent preterm birth and birth of other small vulnerable infants. The live newborns and their mothers will be followed up till 2 months after birth to estimate the intervention effect on neonatal sepsis, puerperal pyrexia, or sepsis in the mothers, antibiotic use during the first 2 months of birth, and cumulative incidence of phenotypic macrolide resistance. Separate independent teams will conduct the intervention delivery and outcome assessment. DISCUSSION: In low-middle income neighborhoods in India, around half of the RTIs are often asymptomatic or unreported and contribute to preterm birth. Our approach involves screening pregnant women at risk of RTI and using azithromycin as a preventive treatment for preterm birth reduction in Indian settings. Additionally, the study will generate data on the intervention effect on child growth, overall antibiotic use, and any concern related to emerging antimicrobial resistance. If the results show a beneficial effect, they could inform policy discussions on the potential use of azithromycin as a preventative treatment for women at risk of RTIs to reduce preterm birth rates. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry-India # CTRI/2024/10/075570, registered on 21 October 2024 https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE0NzM1&Enc=&userName= .
Failure to rescue the trial: lessons from a randomised antibiotic treatment trial in the acute care setting.
van den Eijnde SEJD, Koekenbier EL, van der Linden PD … +4 more , Oosterheert JJ, Bonten MJM, van Werkhoven CH, SAGA study group
Trials · 2026 Apr · PMID 42026686 · Full text
BACKGROUND: A cluster-randomised cross-over trial assessing whether cephalosporin monotherapy is non-inferior to cefuroxime plus short-course aminoglycoside combination therapy for empirical sepsis treatment was terminat...
BACKGROUND: A cluster-randomised cross-over trial assessing whether cephalosporin monotherapy is non-inferior to cefuroxime plus short-course aminoglycoside combination therapy for empirical sepsis treatment was terminated for operational futility due to low enrolment and low protocol adherence. We evaluated barriers to enrolment and treatment compliance. METHODS: Trial enrolment was between May 2022 and May 2023. For this mixed-methods study, we used questionnaires to identify barriers to enrolment and prescribing randomised treatment among local research teams (LRTs) and local clinical staff, which were obtained between January and March 2024. In addition, we investigated screening logs for non-enrolment reasons and determined patient characteristics associated with non-compliance. Clinicians being part of LRT received questionnaires for both roles, with their role clearly indicated per question. RESULTS: In total, 65 questionnaires were completed: 23 by LRT members and 54 by clinical staff (including 12 LRT members). For patient enrolment, screening of inclusion and exclusion criteria was considered challenging in one hospital. According to screening logs, 52.2% of patients were excluded due to at least one exclusion criterion, and 15.6% of eligible patients declined consent for study participation. Primary barriers to prescribe combination therapy were concerns about potential side effects and limited perceived benefit compared to monotherapy. Secondary barriers included supervisors recommending deviations from study protocol. Keeping clinical staff informed and trained during the study was reported as relevant barrier for implementation by LRTs, but considered of low importance by clinical staff. No barriers were reported for monotherapy. CONCLUSIONS: In this study, the main barrier for patient enrolment was the higher than expected proportion of patients with exclusion criteria. The main barrier for treatment compliance was concerns about potential side effects of combination therapy. We recommend quantitative and qualitative pilot studies to identify barriers during the trial design phase, to optimise recruitment strategies and protocol adherence. TRIAL REGISTRATION: European Union Clinical Trials Register, EUCTR2021-001840-83-NL. Registered on 7 July 2021, https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-001840-83.
Effect of pelvic floor muscle training on pelvic floor muscle function and symptoms of dysfunction in women post obstetric anal sphincter injury (OASIS): study protocol for a randomized controlled trial.
de Amorim AC, de Oliveira Lima TV, de Carvalho Frate BN … +2 more , Sartori MGF, GPAP Study Group
Trials · 2026 Apr · PMID 42026644 · Full text
BACKGROUND: Pelvic floor disorders encompass several problems resulting from inadequacies in the pelvic floor muscles (PFMs), especially after childbirth. Obstetric anal sphincter injury (OASIS) is a possible complicatio...
BACKGROUND: Pelvic floor disorders encompass several problems resulting from inadequacies in the pelvic floor muscles (PFMs), especially after childbirth. Obstetric anal sphincter injury (OASIS) is a possible complication of vaginal birth that may significantly affect quality of life. Factors related to the pregnant woman, childbirth, and the newborn can increase the risk of developing OASIS. METHODS: This study encompasses a prospective, randomized clinical trial design with parallel groups. Women diagnosed with OASIS are recruited within 60 days of giving birth. The control group receives standard postpartum care, and the intervention group receives standard care plus a PFMs training program for 12 weeks. Participants are assessed in three in-person and two online sessions throughout the study. The study is conducted at a single center. The primary outcome will be pelvic floor muscle function assessed using the PERFECT scheme, dynamometry, and surface electromyography. Secondary outcomes will include pelvic floor dysfunction symptoms (Australian Pelvic Floor Questionnaire), self-efficacy, and subjective cure. Data will be analyzed using intention-to-treat principles, with appropriate parametric or non-parametric tests. DISCUSSION: This study aims to investigate the effect of PFMs' training in postpartum women with OASIS on PFMs' function and pelvic floor disorder symptoms. PFMs' training is expected to improve PFMs' function, reduce pelvic floor disorder symptoms, and provide an effective therapeutic option for postpartum women with anal sphincter injuries. This study provides significant results on the effectiveness of PFMs' training as an intervention for women with OASIS, contributing to improving the quality of life of these patients. This study will provide evidence on the effectiveness of pelvic floor muscle training in postpartum women with OASIS and may contribute to improving clinical management in this population. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC) (registration number: RBR-32z6gw2, registered 4 April 2024). Study protocol version 1.
The ICARUS project: study protocol for a randomised controlled trial Investigating aCute heArt failuRe decongestion guided by lung UltraSonography.
Leidi A, Mann T, Gosselin P … +10 more , Bedulli M, Esposito F, Schneider C, Parent T, Combescure C, Desmettre T, Reny JL, Stirnemann J, Grosgurin O, ICARUS study group
Trials · 2026 Apr · PMID 42021403 · Full text
BACKGROUND: Acute congestive heart failure (AHF) is a leading cause of hospital admission, with decongestion serving as the cornerstone of its treatment. In the absence of congestion-specific quantitative measures, howev...
BACKGROUND: Acute congestive heart failure (AHF) is a leading cause of hospital admission, with decongestion serving as the cornerstone of its treatment. In the absence of congestion-specific quantitative measures, however, undertreatment often occurs and it is associated with an increased risk of readmission. Lung ultrasonography (LUS) has high accuracy for detecting extravascular lung water. Its use for guiding decongestion in ambulatory patients has shown a reduction in hospital admission and urgent outpatient visits, whereas data are lacking for AHF inpatients. Our aim is to investigate the effect of a LUS-guided decongestive therapy on early clinical outcomes, as compared to physical examination, in hospitalised AHF adults. METHODS: The ICARUS project is a multicentric, multi-blinded, randomised, controlled superiority study, aiming to recruit 222 adult, hospitalised AHF patients with raised values of natriuretic peptide. Participants will be randomised to a decongestive strategy guided by either daily LUS findings (8-point protocol) or daily physical examination. The randomisation will be stratified by study centre and inclusion delay (i.e. within 24 h or more). The primary outcome is the number of days spent alive and out of hospital in a 40-day timeframe from study inclusion (DAOH-40). Secondary outcomes include successful decongestion, length of hospital stay (index hospitalisation), early readmission and mortality, dyspnoea and quality of life (EQ-5D-5L). DISCUSSION: Incomplete decongestion at discharge is frequent in patients hospitalised for AHF and it is strongly associated with rehospitalisation and mortality. There is a need to clarify the role of LUS as a guide for decongestive therapies. The ICARUS project will provide strong evidence on the usefulness of LUS as a guide for decongestive therapy in hospitalised AHF patients. TRIAL REGISTRATION: The present protocol is registered in ClinicalTrials.gov (NCT06465498, registered 20 June 2024, https://clinicaltrials.gov/study/NCT06465498 ) and in the Swiss human research platform HumRes of the Federal Office of Public Health (CCER 2024-00268).
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe