Trials最新文献

Background: Estimands are increasingly used in randomised trials to clarify research objectives. The ICH E9(R1) addendum sets out five attributes necessary to describe a well-defined estimand. However, the addendum was primarily developed for individually randomised trials. There is growing recognition that estimand descriptions for cluster randomised trials, where groups of individuals are randomised, may require specification of additional considerations. We conducted a Delphi study to assess stakeholder views on additional items for inclusion in a consensus extension of the ICH E9(R1) for cluster randomised trials.

Methods: We invited experts in estimands and cluster randomised trials to participate in a modified Delphi process to identify critical items for describing estimands in cluster randomised trials. The research team generated an initial list of eight items and definitions. Across three Delphi rounds, panellists scored items, suggested additional items, and provided open-ended rationales for responses. The consensus threshold was set as ≥ 70% of respondents rating an attribute as "essential" (i.e. score of ≥ 7 on a 9-point Likert scale) and < 15% of respondents rating the item as "not important" (i.e. a score of ≤ 3).

Results: Seventy-three (52%) invited individuals participated in Round 1. Response rates were 85% in Round 2 and 95% in Round 3. Panellists included largely statisticians (62, 85%) and clinical trialists (18, 25%). After Round 1, one additional item was added for Round 2 inclusion. After Round 3, five items met consensus criteria: how individuals and clusters are weighted, population of clusters, exposure time of clusters and individuals to the intervention, whether treatment effects are marginal or cluster-specific, and handling of cluster-level intercurrent events.

Conclusions: This Delphi identified expert consensus around the importance of several key items for defining estimands in cluster randomised trials. These results can inform the development of consensus guidance outlining the set of attributes to describe when defining estimands for cluster randomised trials.

Background: Temporomandibular Disorders (TMD) are musculoskeletal disorders that affect the chewing structures and has a complex and multifactorial etiology. A biopsychosocial approach is recommended for the management of these disorders considering the multifactorial nature of TMD etiology. The aim of this study is to compare the effect of condensed Pain Science Education (PSE) program (2 initial sessions of 75 min) versus longitudinally administered PSE (6 sessions of 25 min) combined with manual therapy and neck motor control exercises (NMCE) on primary outcomes-pain intensity and disability-and secondary outcomes - mandibular range of motion, pain self-efficacy, fear of movement, global perceived effect of improvement, empathy, knowledge about pain neuroscience, beliefs about pain, exercise adherence, and pain catastrophizing-in patients with painful TMD.

Methods: This study will be a randomized controlled trial with a sample of 148 participants. Participants will undergo a screening process to identify TMD according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), aged 20 to 60 years, of both sexes, and then the volunteers will be randomized into two groups (G1: Condensed PSE + Manual therapy/orofacial and NMCE vs. G2: Longitudinal PSE + Manual therapy/orofacial and NMCE). The exercise intervention will take place once a week for 8 weeks, conducted by a physiotherapist, with each session lasting 1 h. The interventions will be administered by trained care providers. The primary outcomes will be pain intensity and disability, assessed using the numeric pain rating scale and the Craniofacial Pain and Disability Inventory (CF-PDI), respectively. For statistical analysis, a linear mixed models considering time and groups as factors will be used. A significance level of p < 0.05 will be considered.

Discussion: To date, no randomized controlled trial has yet been conducted to compare the effect of different modes of PSE delivery on pain intensity and disability in patients with painful chronic TMD.

Trial registration: NCT06259344. Registered on February 14, 2024. https://classic.

Clinicaltrials: gov/ct2/show/NCT06259344.

Background: Newborns requiring invasive mechanical ventilation are at high risk of neurodevelopmental impairment, prolonged hospitalisation, and increased mortality. Treatment guided by cerebral oximetry monitoring has been proposed to reduce morbidity and mortality.

Methods: The SafeBoosC-IIIv trial is a multicentre, parallel-group, randomised clinical trial. The trial will be conducted in two steps. This is a statistical analysis plan for step one. The objective of step one is to assess whether treatment guided by cerebral oximetry monitoring, compared with usual care, increases the number of hospital-free days in newborns receiving invasive mechanical ventilation. Inclusion criteria are gestational age ≥ 28 + 0 weeks, postnatal age less than 28 days, expected to receive invasive mechanical ventilation (intubation) for at least 24 h, and a cerebral oximeter available so monitoring can be started within 6 h after initiation of invasive mechanical ventilation. Exclusion criteria are suspicion of or confirmed brain injury or congenital heart malformation likely to require surgery. A total of 1610 participants will be randomised 1:1 to treatment guided by cerebral oximetry monitoring or usual care. The primary outcome will be hospital-free days within 90 days of randomisation, which will be analysed with the van Elteren test stratified by 'centre'. This statistical analysis plan provides a detailed description of the planned analyses, including methods for handling missing data and assessing statistical assumptions. Analyses will follow the intention-to-treat principle and will be performed independently by two statisticians.

Conclusion: This statistical analysis plan describes the planned statistical analyses in detail for step one of the SafeBoosC-IIIv trial.

Trial registration: ClinicalTrials.gov NCT05907317. First submitted on 8 June 2023, https://clinicaltrials.gov/study/NCT05907317.

Background: Excessive earwax causes unwanted symptoms such as hearing loss, tinnitus, discomfort and changes in the quality of one's own voice. The NHS Audiology Wax Removal Service in North Wales recommends the use of olive oil as a pretreatment wax softener administered as either drops or spray prior to microsuction. For one in four patients microsuction is unsuccessful at the first attempt. Anecdotal evidence suggests that the administration of olive oil as a spray is a more effective pretreatment. This trial aims to explore whether administering olive oil pretreatment softener is more effective when administered as drops or spray.

Methods: This two-arm cluster randomised control trial will be conducted within the existing NHS Audiology wax removal service in North Wales from January to July 2025. This pragmatic trial involves 26 NHS GP practices (clusters) and compares the administration methods of olive oil pretreatment via drops and spray. A sample size of 1,742 participants (67 in each of the 26 practices) was calculated as sufficient to determine a clinically significant difference. Presumed consent is used for all eligible patients seen within the wax removal service. Patients will be advised to source and self-administer three drops or sprays of olive oil for seven days before attending a wax removal microsuction appointment with an audiology practitioner where routine anonymized data will be collected. The primary outcome is whether wax removal is successful, as assessed via visual examination. The secondary outcomes include: improvements in self-reported symptoms, the amount of residual wax following microsuction and the number of adverse events. Statistical analyses will be conducted with an intention-to-treat design to compare outcomes between the groups.

Discussion: This RCT aims to investigate whether administering olive oil as a pretreatment wax softener via drops or spray affects the outcome of wax removal. The outcome of this trial will inform future recommendations to patients and improve service effectiveness and efficiency by reducing the need for repeat visits. The results will be shared nationally and used to inform national guidance on wax removal.

Trial registration: ISRCTN, ISRCTN28211073. Registered 23 December 2024, https://www.isrctn.com/ISRCTN28211073?q=earwax&filters=&sort=&offset=1&totalResults=3&page=1&pageSize=10.

Background: Children living in regional and rural Australia have diminished health outcomes and are more likely to be developmentally vulnerable on one or more domains compared to urban peers. Despite this, children in regional and rural Australia often cannot access specialist care due to lack of availability, financial constraints, or waiting times of over 12 months. Strengthening Care for Rural Children (SC4RC) aims to evaluate an integrated general practitioner (GP)-paediatrician model of care in rural communities to enhance the quality of paediatric care by ensuring children receive timely, accessible care within their communities by reducing referrals to public and private paediatric services.

Methods: SC4RC is a stepped-wedge randomised controlled trial of 22 general practice clinics in regional and rural Victoria and New South Wales, Australia. Control data for each general practice clinic will be collected for a minimum of 1 month and each clinic will be randomly allocated a start month, with the intervention running for 11 months at each clinic. The intervention will consist of fortnightly GP-paediatrician co-consultation sessions, weekday phone and email paediatrician support for GPs, and access to a paediatric online community of practice via a Project ECHO™ series. The primary outcome is the proportion of paediatric (0 to <18 years) GP appointments that result in a referral to a paediatric service (hospital emergency departments, outpatient clinics, or private paediatricians) during the intervention period compared with the control period. Secondary outcomes include GP quality of care across 17 common childhood conditions, GP confidence in paediatric care, family confidence in GP care, and the sustainability of the SC4RC model. Integral to the project is our consumer engagement framework which will inform the translation and implementation of the project. An implementation evaluation will assess the acceptability, adaptability, and scalability of the model, whilst a health economic evaluation will measure the cost-effectiveness/benefit of the intervention.

Discussion: This protocol paper outlines how we will partner with primary care organisations and paediatric services to implement and evaluate SC4RC in some regional and rural communities in Victoria and NSW.

Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12623000550606. Registered on 23 May 2023.

Adolescent mothers in the Caribbean represent a high-need, under-served population facing overlapping reproductive, mental health, and social challenges. Despite the urgency of these needs, few randomized controlled trials (RCTs) target this group using culturally tailored, integrated care models. The Teen motHers' ReproductIve and behaVioral health intErvention (THRIVE) was conceptualized in Barbados in April 2024 as a randomized trial to evaluate such a model. However, as of today, THRIVE has not launched due to prolonged Institutional Review Board (IRB) delays and cultural sensitivities surrounding adolescent pregnancy-barriers that reflect broader systemic challenges common across low- and middle-income country (LMIC) contexts. In response, a parallel initiative-the Project Amai-was launched as a community-driven, service-based intervention outside the traditional RCT framework. Prioritizing cultural responsiveness, youth engagement and leadership, and low-barrier access, Amai reached a cohort of marginalized adolescent mothers and achieved high retention, program graduation, and improvements in agency and well-being within 8 months. This commentary contrasts the stalled progress of THRIVE with the rapid implementation of Amai to examine how institutional, infrastructural, and cultural factors shape the feasibility of equity-focused trials. We draw lessons for trialists working in under-resourced settings and suggest that advancing diversity, equity, and inclusion in trials requires adaptive strategies-including pragmatic designs, regional ethics collaboration, and broader outcome measures in the Caribbean. These insights contribute to emerging models of inclusive global health research and offer actionable guidance for designing trials and programs that are not only methodologically rigorous but also socially just and accessible to those most in need.

Background: The implantation of cardiac implantable electronic devices (CIED) is the treatment of choice for the prevention of sudden cardiac deaths in high-risk patients. Given the comorbidities, this superficial surgical intervention is mostly performed in local anaesthesia. Triggered by the upcoming opioid crisis, the burden of postsurgical pain has gained popularity, as adequate perioperative pain management is a cornerstone in the prevention of persistent opioid use. Aim of this study is to assess the perioperative pain management of local anaesthesia versus pectoserratus plain/interpectoral plain (PSP/IPP) block for submuscular CIED implantation.

Methods: In a single-centre, prospective, single-blinded, two-group randomized trial, 80 patients undergoing submuscular CIED implantation will be randomized to receive a PSP/IPP with ropivacaine 0.375% (intervention group) or a LA with lidocaine 2% (control group). The primary outcome is the Quality of Recovery-15 (QoR-15) assessed 24 h after surgery. Secondary endpoints include the intraoperative additional LA administration; the postoperative analgesic consumption; the need and dose of additional analgesia; Visual Analogue Scale (VAS) after 2, 4, 6, 12, and 24 h; and VAS-AUC and VAS groups <30 mm/30-60 mm/>60 mm.

Discussion: This prospective, randomized, controlled, and single-blinded trial aims to assess if a PSP/IPP with ropivacaine affects the postoperative QoR-15 score compared to a conventional local anaesthesia with lidocaine in patients undergoing submuscular CIED implantation. Given the impressively high rate of persistent opioid use (POU) in patients after CIED, results from this study could help improve the perioperative pain management.

Trial registration: EUDRA CT Number: 2023-508997-27. Registered on 20 September 2024. https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-508997-27-00.

Background: Antibiotic resistance (ABR) is a global health threat, significantly driven by its misuse. The World Health Organization stresses the need for better antibiotic use to combat ABR through behavioral change interventions. Visual storytelling, which merges narrative with visuals, can enhance health behaviors by boosting cognitive and emotional engagement. In Pakistan, more than half of the population lack access to mobile phone, limiting digital health solutions. To address this gap, we developed a culturally tailored Visual Storytelling for Antibiotic Adherence (VISTA) intervention - a theory-driven sticker-based tool - to improve antibiotic adherence among urinary tract infection (UTI) patients in low-connectivity settings.

Methods: In this parallel, two-arm superiority randomized controlled trial, participants with physician-confirmed uncomplicated UTI who have filled an oral antibiotic prescription will be recruited from six tertiary care hospitals in Khyber Pakhtunkhwa, Pakistan. The participants will be randomized in a 1:1 manner to receive either the VISTA intervention or standard care. The VISTA intervention was developed based on nudge theory, guided by the Taxonomy of Choice Architecture framework, and complemented by the MINDSPACE (messenger, incentives, norms, defaults, salience, priming, affect, commitments, and ego) framework. It was developed and validated through a Delphi method, assessing expert feedback, and refined based on a patient understanding study. The intervention sticker uses contrasting colors-red (non-adherence: bacteria evolving into "superbugs") and green (adherence: antibiotics fully eradicating bacteria)-to communicate the consequences of incomplete versus complete adherence. The primary outcome is adherence, measured by pill count at the initial follow-up. Secondary outcomes include UTI recurrence, knowledge, and attitudes regarding antibiotic adherence. Analysis will follow both intention-to-treat and per-protocol principles.

Discussion: This randomized controlled trial will evaluate a theory-driven, scalable intervention for low-resource, low-connectivity settings, aligning with WHO priorities for ABR mitigation. It addresses the patient support gap caused by limited digital access. Pill counts provide an objective adherence measure, though they may miss intentional non-adherence; including UTI recurrence as a secondary outcome helps mitigate this. Cultural tailoring through expert panels and patient feedback aims to enhance relevance and applicability across similar contexts, improving generalizability.

Trial registration: The trial was registered with ClinicalTrials.gov (registered: March 13, 2025, NCT06885658, https://clinicaltrials.gov/study/NCT06885658).

Background: Young transgender women are disproportionately impacted by HIV in comparison to other risk groups in the United States. Despite research documenting this vulnerability, few interventions have been developed and tested to reduce their risk and none to evaluate effects on HIV incidence. The LifeSkills Mobile app addresses the specific structural, developmental, and interpersonal challenges to HIV prevention among young transgender women ages 16-29 and is adapted from LifeSkills, a group-based intervention with evidence of efficacy to reduce sexual risk for HIV. The LifeSkills Mobile app was developed to increase the reach of LifeSkills, an evidence-based intervention, broadly via mobile access.

Methods: This study is a digital, limited interaction national randomized controlled trial. Participants are randomized (1:1) to the LifeSkills Mobile intervention or an HIV prevention standard of care condition. The study aims to enroll up to 5000 participants with follow-up visits at 6-month intervals up to 48 months, depending on the date of enrollment. The primary endpoint is incident HIV infection (confirmed via lab test or medical records). A log-rank test will be used to evaluate the null hypothesis of no difference in survival (cumulative HIV incidence) between the two study arms. Secondary endpoints are Behavioral risk is defined as total condomless sex acts in the context of insufficient PrEP protection and PrEP care linkage, initiation, and retention/constancy over time.

Discussion: This study will test the efficacy of the LifeSkills Mobile intervention on HIV incidence among young transgender women, ages 16-29 across the US. TRIAL REGISTRATION {2A, 2B}: ClinicalTrials.gov NCT05018611. Registered on August 24, 2021.