Trials最新文献

Background: Neurosurgical trials have a high burden on participants, which underscores the need to involve patients, carers, and the public in trial design to ensure their needs and expectations are met. However, there is currently limited guidance on the establishment, retention, and role of patient and public involvement (PPI) groups in neurosurgical trials, beyond generic guidance, which may contribute to the very low use of PPI in surgical trials. To promote meaningful public involvement in neurosurgical trials based on lived experience, we evaluated our public involvement and developed actionable recommendations. We also co-created a novel support package for neurosurgical trial participants.

Methods: During the planning of a neurosurgical trial, 14 individuals formed a PPI group, including people with Parkinson's, care partners, and charity staff. This reflective evaluation of the group used mixed-methods data collected using the PIRIT Tracking Tool, meeting polls/reflections, and reflective diaries. Our PPI group co-created the resulting reflections and recommendations, which follow the UK Standards for Public Involvement framework. The support package was co-designed in two online workshops, with 12 participants, including people with Parkinson's and care partners.

Results: Our recommendations for meaningful PPI cover inclusive opportunities, working together, support and learning, governance, communications, and impact. For example, we recommend providing all public contributors with an approachable point of contact, defining a clear plan for evaluation and addressing concerns identified through evaluation, and ensuring co-created tasks have clearly defined, tangible outcomes. The support package for neurosurgical trial participants spans before (psychological assessment and support; trial buddies; videos and written case studies from participants in similar trials), during (medical advice and support; Patient Liaison; psychological support), and after (medical, social, and psychological support) trial support.

Conclusions: Our practical, generalisable recommendations and novel participant support package aim to strengthen public involvement and enhance care in neurosurgical trials. The support package needs testing within a trial to determine its feasibility and effectiveness.

Background: Major depressive disorder (MDD) is highly prevalent and associated with substantial disease burden and significantly reduced life expectancy. Physical activity (PA) has been shown to reduce depressive symptoms to a similar extent as antidepressant medication. Despite this evidence, individuals with MDD engage in lower levels of PA and exhibit higher levels of sedentary behavior. Structural, physical, and psychological barriers hinder PA engagement. PA coaching offers a promising strategy to overcome these barriers and promote sustainable behavior change. Previous research highlights the importance of addressing affective responses to PA in interventions. Moreover, the support of technology-based tools, such as wearables, seems promising. This study aims to investigate the short- and long-term effects of a new PA coaching approach on PA behavior, depression severity, and quality of life in outpatients with MDD. Potential mechanisms of behavior change and participant experiences are also examined.

Methods: This study uses a three-arm randomized controlled trial (RCT) design and is conducted at a psychiatric day clinic in German-speaking Switzerland. A total of 114 individuals aged 18 to 65 years with a clinical diagnosis of MDD (ICD-10: F32 and F33) are recruited on an ongoing basis and randomly assigned to one of three groups: (1) A 10-week PA coaching program based on interest and experience in PA, supported by a wearable smart ring for self-monitoring; (2) the same 10-week program extended by an additional, remote 26-week cognition-based coaching phase; or (3) a control group receiving treatment as usual along with written current PA guidelines. Data is collected at three measurement timepoints: 2-4 weeks after the start of day clinic treatment (baseline), after the 10-week coaching phase (post), and after a 6-month follow-up period (follow-up). The primary outcome is the change in device-measured PA over time (baseline, post, and follow-up), measured via Fibion^® accelerometer, and analyzed using linear mixed models.

Discussion: A new PA coaching program is introduced to counteract low PA levels observed in individuals with MDD. By combining affective with cognitive components of behavior change, the intervention aims to promote a sustainable increase in PA and ultimately improve mental and physical health and quality of life.

Trial registration: DRKS: DRKS00036209. Registered on 08 May 2025.

Background: Traumatic brain injury (TBI), particularly mild forms resulting from blast exposure, remains a diagnostic challenge among veterans due to delayed symptom onset and overlapping psychological conditions such as posttraumatic stress disorder. Current diagnostic methods rely heavily on subjective assessments, contributing to underdiagnosis and inconsistent care. Electroencephalography (EEG) offers a non-invasive, real-time measure of cortical activity with high temporal resolution, making it a promising tool for objective TBI assessment. This sub-study, nested within a randomized controlled trial evaluating hyperbaric oxygen therapy (HBOT) for veterans with TBI, investigates EEG as both a diagnostic modality and a therapeutic monitor.

Methods: This sub-study adopts the same triple-blinded, randomized, parallel-group design as the parent trial. Participants are veterans with mild to moderate TBI, randomized to receive either HBOT or a sham treatment. EEG data are collected at three time points: baseline (pre-treatment), midpoint (18-21 dives), and post-treatment (2 weeks after completion). EEG recordings are performed during standardized cognitive and motor tasks using a 32-channel wireless headset. Primary outcomes include event-related potential amplitudes and alpha-band spectral power, analyzed for longitudinal changes and group differences. Secondary outcomes include latency measures, spectral power across additional frequency bands, and functional connectivity metrics. Data are modeled using repeated measures analysis to assess treatment effects and individual trajectories.

Discussion: This sub-study aims to validate EEG as a scalable and objective tool for diagnosing and monitoring TBI in clinical settings. By identifying electrophysiological signatures associated with injury severity and treatment response, EEG may enhance diagnostic precision and support personalized care strategies. The integration of EEG within a larger therapeutic trial framework allows for comprehensive evaluation of its clinical utility. Findings may inform future protocols for TBI assessment and contribute to the development of neurophysiological biomarkers that complement existing symptom-based approaches.

Trial registration: ClinicalTrials.gov NCT06581003. Registered on 30 August 2024.

Background: Major depressive disorder (MDD) is a significant contributor to the global burden of disease, with a high prevalence in Pakistan. MDD is treatable, and eye movement desensitization and reprocessing (EMDR) therapy is recognized as an effective treatment worldwide. However, EMDR therapy, rooted in Western psychological frameworks, may require cultural and methodological adaptation to fit clients' needs in Pakistan. Notably, there is a lack of research on adapting EMDR therapy in Pakistan, and scarce studies on its effectiveness through online modalities. To bridge these research gaps, this study has two aims: first to develop an adapted DeprEnd EMDR therapy protocol in Pakistan; second, to test its feasibility, relevance, and clinical effectiveness across in-person and online modalities.

Methods: This research adopts a mixed-mode exploratory sequential randomized controlled trial design. In the first phase, an exploratory qualitative approach will be utilized to culturally and methodologically adapt DeprEnd EMDR therapy protocol through narrative review and focus group discussion. Data will be qualitatively analyzed. This phase has been previously reported in a separate peer-reviewed publication. In the second phase, a randomized controlled trial design will be used to test the feasibility, relevance, and clinical effectiveness of the adapted DeprEnd EMDR therapy protocol. Initially, it will be pilot tested among 25 handful clients, and later an estimated sample of 80 clients will be selected to test it on a large scale. Clients will be randomized via a covariate-adaptive technique to in-person and online arms with a 1:1 ratio. Symptom-related data will be collected at the baseline, midpoint, post-treatment, and follow-up stages. Data will be analyzed using a combination of univariate and multivariate statistics.

Discussion: This research conducts the first known scientific adaptation and clinical testing of the DeprEnd EMDR therapy protocol in Pakistan. Through systematic adaptation and assessment of its feasibility and clinical effectiveness, this protocol is positioned to be scalable, showing potential for broader dissemination across South Asia. It contributes a vital framework for culturally sensitive mental health interventions that bridge global evidence-based practices and local sociocultural needs. This study paves the way for collaborative efforts to optimize trauma-focused psychotherapies in low-resource contexts, thus promoting health equity in the region.

Trial registration: The initial study protocol was registered in the ClinicalTrials.gov database under registration no: NCT-06439043. Last Updated:01/21/2025 and Initial Release:05/27/2024.

Background: Nocturia (i.e., waking to void during the primary sleep period) of two or more times per night affects nearly one-third of older adults and can have a severe impact on sleep, contributing to insomnia symptoms. Current treatment approaches for nocturia often overlook non-lower urinary tract factors that may contribute to nighttime awakenings. Nocturia management, for example, may benefit from more effective integration of cognitive behavioral therapy for insomnia (CBT-I) principles that address other factors underlying insomnia symptoms, and early evidence suggests it also reduces nocturia and the bother it causes. Because nocturia treatment crosses specialties, coordinated delivery of urological and sleep therapies is a treatment barrier. The overall purpose of this trial is to determine whether a promising coordinated, integrated behavioral, non-pharmacological, non-surgical treatment that simultaneously addresses both the urological and insomnia factors contributing to nocturia is efficacious for improving nocturia, sleep, and daytime function.

Methods: This multicenter parallel-group randomized, efficacy trial compares a 5-week integrated behavioral treatment program delivered by a single interventionist (psychologist, nurse practitioner, or physician assistant) to a health education control program in adults aged 60 years or older (proposed n = 192) recruited from sites in Atlanta and Los Angeles, who report typically getting up to urinate two or more times per night (International Consultation on Incontinence Questionnaire-Overactive bladder [ICIQ-OAB] nocturia item) and insomnia symptoms (Insomnia Severity Index > 7). The integrated program includes components of CBT-I and pelvic floor muscle exercise-based behavioral therapy for nocturia. The primary outcome is ICIQ-OAB-measured nocturia frequency 4 months after randomization. Secondary outcomes are sleep diary-measured wake after sleep onset (mean minutes) and Insomnia Severity Index total score.

Discussion: The interdisciplinary trial team has developed a program aimed at improving nocturia symptoms and overall sleep of older adults in an efficient and safe manner. The integrated behavioral program has the potential to address nocturia, which is a challenging symptom because it has many etiologies that cross multiple specialties. Findings will provide rigorous evidence of the efficacy of the integrated behavioral treatment program to reduce nocturia frequency as well as sleep disturbance in older adults.

Trial registration: Clinicaltrials.gov NCT06110091, registered 10/25/2023.

Background: To end the tuberculosis (TB) epidemic, the WHO recommends implementing active case-finding to increase TB detection, as well as the provision of TB preventive treatment (TPT) in contacts of people with TB. However, the scale-up of both strategies remains limited in high TB-burden countries such as Thailand. Despite the country's highly decentralised healthcare system, significant inequalities remain in access to care, particularly in vulnerable populations. We designed an intervention study investigating the effectiveness and feasibility of a novel strategy combining active case-finding and the implementation of short-course TPT in households of newly diagnosed adults with TB in Thailand.

Methods: This is a pragmatic phase IV stepped-wedge cluster-randomised trial conducted in 20 provincial hospitals (clusters). The study population comprises household members who were exposed within the last 3 months to adults with newly detected bacteriologically confirmed TB. The intervention combines an educational video to the index TB case, provision of an invitation card to household contacts for free TB screening at the facility, with a transport voucher, and support from village or urban health volunteers. Household contacts without active TB are offered TPT regimens according to age: 1-month rifapentine-isoniazid (1HP), 3-month rifapentine-isoniazid (3HP) or 3-month rifampicin-isoniazid (3HR). In the control phase, TB staff implement the current standard of care, including verbal information to persons newly diagnosed with TB on the need to screen their household contacts and provision of standard TPT. Hospitals shift from the control to the intervention phase every 3 months in four randomised sequences until all clusters apply the intervention. Generalised linear mixed models will be used to compare the intervention outcomes versus the standard of care, controlling for clustering and confounding by time.

Discussion: Active case-finding and systematic TPT in at-risk populations is currently limited in Thailand. This protocol incorporates pragmatic design features with a participant-centred approach to assess the effectiveness, feasibility and acceptability of a combined strategy including systematic screening of household contacts, active case-finding and TPT provision. If successful, this strategy will likely contribute to TB elimination in Thailand and beyond.

Trial registration: The study is registered at ClinicalTrials.gov NCT05581212 on April 3rd, 2024, and is currently recruiting.

Background: Knee osteoarthritis (KOA) is one of the most prevalent health issues, affecting approximately 67% of women over 60 years old. Clinical guidelines recommend individualized muscle training to treat this condition. However, a lack of human and financial resources hinders the delivery of this treatment. In response to this limitation, group training may be an alternative. Although a few studies have compared group and individual exercise for knee OA, none have tested the non-inferiority of group-delivered circuit training specifically in elderly women. Therefore, this study aims to compare the non-inferiority of a group-delivered muscle training program to the same individually delivered training in clinical and functional aspects in elderly women with KOA.

Methods: This is a randomized controlled non-inferiority trial with two arms, parallel groups, blinded evaluator, conducted in Petrolina-PE, evaluating women aged 60 or older. Participants randomly assigned will undergo an 8-week training, either in individual sessions (control group-IB) or as part of a group (intervention group-GB) of four participants, supervised by a physical therapist. Blind assessments at baseline, immediately post-intervention, and 4 weeks post-intervention will include feasibility, safety, and satisfaction analysis of the training program; pain; quality of life; and physical function. Data will be analyzed using the Statistical Package for Social Sciences (SPSS) version 22. Estimated marginal means of each clinical and functional outcome for both groups (IB and GB) will be compared using mixed-effects generalized linear models. The primary analysis will test our main hypothesis that group training is non-inferior to individualized training regarding the primary outcome: relative reduction (%) in the WOMAC questionnaire pain subscale. Confidence intervals of 95% will be calculated. A significance level of p < 0.05 will be adopted in all analyses.

Discussion: Expected results suggest that a group-based approach is not inferior to an individual one in this population.

Trial registration: Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-5bq9jh3. Registered on 18 August 2023. Link: http://www.ensaiosclinicos.gov.br; Universal Trial Number (UTN) of World Health Organization: U1111-1289-2580.

Background: Older adults represent a growing proportion of Emergency Department (ED) attendees and experience high rates of adverse outcomes post discharge from the ED such as functional decline, increased risk of institutionalisation and unplanned hospital readmissions. In response to these issues, there has been a proliferation of studies evaluating various interventions to mitigate these adverse outcomes. However, this expansion of research has been hampered by a lack of agreement on 'what to measure' in these studies and a lack of attention to the measurement of patient/ service user reported outcomes. To address these issues, we aim to develop a Core Outcome Set (COS) for intervention studies based, or initiated, in the ED with older adults.

Methods: A five-stage approach will be undertaken to develop the COS in conjunction with a Public and Patient Involvement (PPI) panel of older adults and family carers. To generate a long list of outcomes, three stages will be undertaken. 1. A scoping review to identify commonly reported outcomes in intervention studies based/initiated in the ED, associated instruments and measurement timepoints. 2. A rapid qualitative evidence synthesis to identify outcomes of importance to older adults attending the ED. 3. Participatory research methods will be employed to identify outcomes of relevance to older adults and their families/ caregivers, health care Providers and research stakeholders. To achieve consensus on outcomes and associated instruments to include in the COS, a further two stages will be undertaken. 4. A Real-Time Delphi survey study and consensus meeting with key stakeholders to reach consensus on inclusion of outcomes in the COS. 5. A search for existing instruments to evaluate each outcome identified in stage 4 will be conducted. Identified instruments will be evaluated, and a consensus meeting will be held to select one outcome measure instrument for each outcome included in the COS.

Discussion: A COS for research with older adults in the ED will serve to enhance future clinical trials, systematic reviews and clinical guidelines by enhancing the availability of comparable data and by ensuring outcomes that matter to all stakeholders are represented.

Trial registration: Development of a Core Outcome Set for research studies with older adults in the Emergency Department-CREAT-ED (COMET) initiative 2749 COMET Initiative | Development of a Core Outcome Set for research studies with older adults in the Emergency Department-CREAT-ED. https://www.comet-initiative.org/Studies/Details/2749.

Background: Acute cholangitis is an infection of the biliary tract that is managed with adequate biliary drainage combined with antibiotic treatment. The international Tokyo Guidelines 2018 recommend 4 to 7 days of antibiotic treatment after adequate biliary drainage, but observational data suggest shorter treatment may be sufficient. We assessed whether 1 day of antibiotic treatment is non-inferior to 4-7 days of antibiotic treatment for acute cholangitis after adequate biliary drainage.

Methods: The COBRA-trial is a multicentre, open-label, parallel group randomized controlled non-inferiority trial with blinded outcome assessment. A total of 416 patients with acute cholangitis will be randomly assigned in a 1:1 ratio to the intervention group (1 day of antibiotic treatment after adequate biliary drainage) or to the control group (4-7 days of antibiotic treatment after adequate biliary drainage). Patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction, or distal biliary stent dysfunction are eligible. Randomization will take place once adequate biliary drainage is achieved by ERCP. Main exclusion criteria are concomitant pancreatitis, liver abscess, cholecystitis, and another infectious diagnosis at the time of randomization, use of systemic maintenance antibiotics, and specific immunosuppressants. Patients will be stratified for blood culture results at the time of randomization and aetiology of cholangitis. The primary endpoint is clinical cure, defined as the patient being symptom-free by day 14, with no relapse or death occurring by day 30. Secondary endpoints include 30-day and 90-day all-cause mortality, relapse of cholangitis by day 90, time from ERCP to first relapse, any other subsequent infection requiring antibiotic treatment within 90 days, duration of initial hospital stay, number of days treated with antibiotics by day 30, subsequent infections with multidrug resistant (MDR) bacteria, quality of life, and cost-effectiveness.

Discussion: This trial assesses whether a short course of antibiotic treatment for acute cholangitis is as safe and effective compared to a longer course of antibiotic treatment. If confirmed, the results could substantially reduce antibiotic exposure and healthcare resource utilization, thereby contributing to global efforts to minimize unnecessary antibiotic treatment.

Trial registration: ClinicalTrials.gov NCT05750966, registered on March 2nd, 2023.