Trials最新文献

In 2024, Denmark led the European Union in clinical trials per capita. This is celebrated as a marker of innovation, signalling Denmark's research capacity and attractiveness to the global industry. Yet, trial volume alone provides a limited account of clinical research value and hides a more troubling reality: research is concentrated in commercially lucrative areas such as oncology and Alzheimer's, while children, pregnant individuals, older adults, those with chronic pain, multimorbidity, or less profitable conditions are often overlooked. This mismatch is not merely a policy oversight. It reflects structural and epistemic injustices that determine whose bodies, experiences, and health outcomes are considered research-worthy. Drawing on Denmark as a national case example situated within broader European and international debates, this commentary highlights how inclusion strategies risk focusing on numeric representation rather than justice in knowledge production while also pointing to promising opportunities for inclusive innovation within the clinical research ecosystem in Europe. By moving beyond mere checklist inclusion, there is potential to foster a more equitable, reflective, and justice-oriented approach to participation and knowledge generation, one that benefits patients, researchers, and the broader society.

Background: ProMetrioS is a randomized, blinded, placebo-controlled cross-over trial investigating the effect of a specific multispecies probiotic in patients with endometriosis. The aim of this clinical trial is to determine whether probiotic treatment can significantly modulate gut microbiome composition and functionality in endometriosis patients, particularly parameters associated with the estrobolome.

Methods: This is a double-blinded, randomized, cross-over, placebo-controlled trial. Participants are randomly allocated to receive either 3 g of a probiotic formulation daily or a placebo for 8 weeks in two study phases, separated by a 8-week washout period. The gut microbiome is analyzed at four timepoints: start of thestudy, after phase 1, after the washout phase, and at the end of the study (after phase 2) amplicon sequencing. Quality of life related to endometriosis is assessed using validated questionnaires in the same four timepoints. Our primary endpoint is the favorable modulation of the gut microbiome, particularly with respect to the estrobolome. Secondary endpoints include changes in quality of life, reported symptomatology, and psychophysical condition.

Discussion: The findings of this study will provide the first evidence for the use of a combination of probiotics in the treatment of endometriosis. The results are expected at the end of 2025.

Trial registration: ClinicalTrials.gov (NCT06929364).

Background: Stepped wedge cluster randomized trials (SW-CRTs) have historically been analyzed using immediate treatment (IT) models, which assume the effect of the treatment is immediate after treatment initiation and subsequently remains constant over time. However, recent research has shown that this assumption can lead to severely misleading results if treatment effects vary with exposure time, i.e., time since the intervention started. Models that account for time-varying treatment effects, such as the exposure time indicator (ETI) model, allow researchers to target estimands such as the time-averaged treatment effect (TATE) over an interval of exposure time, or the point treatment effect (PTE) representing a treatment contrast at one time point. However, this increased flexibility results in reduced power.

Methods: In this paper, we use public power calculation software and simulation to characterize factors affecting SW-CRT power. Key elements include choice of estimand, study design considerations, and analysis model selection.

Results: For common SW-CRT designs, the sample size (clusters per sequence or individuals per cluster-period) must be increased substantially, commonly by a factor of 1.5 to 3, but often by much more, to maintain 90% power when switching from an IT model to an ETI model (targeting the TATE over the study). However, the inflation factor is lower for TATE estimands over shorter periods that exclude longer exposure times. In general, SW-CRT designs (including the "staircase" variant) have much greater power for estimating "short-term effects" relative to "long-term effects." For an ETI model targeting a TATE estimand, substantial power can be gained by adding time points to the start of the study or increasing baseline sample size, but surprisingly, little power is gained from adding time points to the end of the study. More restrictive choices for modeling the exposure time or calendar time trends (e.g., splines or linear terms) have little effect on power for TATE estimands but increases power for PTE estimands. If the effect curve is constant after a washout period, a "delayed constant treatment" model that uses exposure time indicators during the washout period but assumes a constant effect thereafter can slightly increase power relative to an IT model that discards washout period data.

Background: Cardiovascular (CV) disease and its risk factors such as hypertension, diabetes, and hyperlipidemia account for most chronic diseases experienced by adults in the US. The use of text-based "behavioral nudges" supports behavior change and self-management of chronic disease. Building upon our previous trial utilizing an artificially intelligent (AI) chatbot for medication adherence, the Chat for Heart Health randomized controlled trial aims to test the comparative effectiveness of 3 text-based methods of delivering "nudges" to change health behaviors to reduce cardiovascular disease risk in patients across 3 safety-net healthcare systems.

Methods: Adult patients ages 18-89 with CV risk factors will be recruited from 3 health systems. A target of 2097 participants will be randomized to 3 study arms: generic text messaging, AI interactive chatbot messaging, and AI interactive chatbot messaging plus pharmacist support. Evaluation of the intervention and the program will be carried out using the RE-AIM and PRISM frameworks. The primary effectiveness outcome is the change in CV risk reduction behaviors as defined by the American Heart Association's Life's Essential 8 score. Secondary outcomes including patient self-efficacy scores, clinical events, healthcare utilization, and facilitators and barriers to implementation and adoption will also be assessed.

Discussion: Our large-scale pragmatic trial engages with patients and health systems who have traditionally not engaged in research, which presented substantial challenges yet will make our results more generalizable to diverse populations. Additionally, we engaged a diverse advisory panel made up of patients, community members, providers, and health systems leaders throughout the study to ensure sociocultural, linguistic, and community relevance. The results of this trial (if the intervention is effective) could lead to broader dissemination of a low-cost intervention to support behavior change to reduce CV risk.

Trial registration: NCT06324981 (3/14/2024), https://clinicaltrials.gov/study/NCT06324981.

Background: The most popular surgical treatment for end-stage hip joint arthritis is total hip arthroplasty (THA). The main problems that occur after THA are pain, functional disability, and reduced quality of life. The primary rehabilitation program for post-THA is conventional physiotherapy, but there is growing interest in complementary therapies that could hasten recovery and enhance results. Pulsed electromagnetic field therapy (PEMF) is a non-invasive treatment that reduces pain, promotes tissue repair, and may improve musculoskeletal outcomes. However, its effectiveness in THA patients is yet unknown, especially in comparison to sham PEMF therapy.

Methods: A single-blind, two-arm parallel-group randomized controlled trial will be conducted with 90 participants aged 18-70 years who have undergone total hip arthroplasty. Participants will be randomized into two groups: group A (n = 45) will receive pulsed electromagnetic field therapy in conjunction with conventional physiotherapy and group B (n = 45) will receive sham pulsed electromagnetic field therapy in conjunction with conventional physiotherapy. The intervention will be administered 4-5 times per week for 2 weeks, with each PEMF lasting 30 min. Participants will be evaluated before (baseline-POD 3) and after the intervention (end of 2 weeks) and administered during a predetermined time frame. The primary outcomes will be a visual analog scale and a Harris hip score for assessing postoperative pain and functional impairment. The secondary outcome will consist of an SF-36 questionnaire to evaluate quality of life and patient satisfaction. Additionally, safety and compliance with the intervention will be observed throughout the study.

Discussion: The purpose of this study is to investigate the possible impact of combining traditional physiotherapy with pulsed electromagnetic field therapy after total hip replacement. By comparing active versus sham PEMF therapy, this study may give fresh perspectives on comprehensive and successful rehabilitation techniques for participants who have undergone total hip arthroplasty by emphasizing pain, functional disability, and quality of life.

Ethics and dissemination: The trial has been reviewed and approved by the Institutional Ethics Committee (Reference no. DMIHER (DU)/IEC/2025/618).

Trial registration: CTRI/2025/03/083475. Registered on 26 March 2025.

Background: Post-COVID condition (PCC) encompasses a heterogeneous spectrum of pathological responses to SARS-CoV-2 infection, with unknown individual predispositions. No evidence-based, curative treatments are available. Many patients therefore resort to off-label use of medications originally developed for other indications. However, the efficacy and safety of repurposed drugs in the context of PCC are unknown.

Methods: RECLAIM is a phase III, randomised, controlled, adaptive platform trial. The trial population consists of adult patients who have had persistent PCC symptoms, including fatigue and/or post-exertional malaise, 12 or more weeks after the onset of a SARS-CoV-2 infection. Randomisation occurs within trial domains. A trial domain consists of one or multiple investigational products (IPs), each to be compared to one usual care arm, or one or multiple IPs, each to be compared to a matching placebo. Within each trial domain, patients can be enrolled if they are eligible for at least one IP and its control. They are randomised with equal probability to each arm for which they are eligible. Trial product use (if applicable) starts as soon as possible after randomisation for a default duration of 12 weeks. Study procedures are implemented remotely, using video consultations, eConsenting, trial product delivery to participants' homes (if applicable), and online questionnaires at baseline, day 1, and weeks 2, 4, 6, 8, 10, 12, and 24. The primary outcome is health-related quality of life at week 12, assessed by Patient-Reported Outcomes Measurement Information System Profile29 (PROMIS-29) physical health summary scores, and is analysed with a Bayesian analysis of covariance model with adjustment for the baseline value. Secondary outcomes include week 12 PROMIS-29 mental health summary scores and topic domain scores; specific PCC symptoms using other patient-reported outcome measures, safety, and tolerability; and durability of treatment responses at week 24. Participants are allowed to participate in only one trial domain at a time, but can be rerandomised into a different trial domain after completing week 24.

Discussion: RECLAIM commenced in February 2025 with an open-label domain including two IP arms (metformin and colchicine) and one usual care control arm. A second placebo-controlled domain, comparing minocycline to a matching placebo, was initiated in February 2026.

Trial registration: European Clinical Trials Information System (CTIS) EUCT number 2024-511580-28-02. Registered on 9 October 2024.

Clinicaltrials: gov identifier NCT07280572. Registered on 11 December 2025.

Introduction: Procedural sedation during dental treatment has been reported to have a high incidence of respiratory depression. Nasal high flow (NHF) therapy uses a mild positive pressure load that improves carbon dioxide washout and reduces rebreathing to improve respiratory function and therefore is widely used to prevent hypoxemia and hypercapnia. We will investigate the efficacy of respiratory support with NHF during dental treatment under procedural sedation.

Methods/design: In a multicenter randomized controlled study, adult patients undergoing dental treatment under procedural sedation were allocated to either a nasal high-flow (NHF) group or a low-flow oxygen group. For sedation, midazolam plus propofol were used according to the guidelines to obtain a moderate sedation level. The primary endpoint is the incidence of hypoxemia, defined as SpO₂ ≤ 90% during intravenous anesthesia. As a secondary evaluation item, the percutaneous CO₂ concentration is evaluated to examine whether it is effective in preventing hypercapnia. Furthermore, we will evaluate sedative and analgesic doses, and examine whether the use of equipment is effective in preventing the occurrence of hypercapnia and hypoxemia.

Discussion: The purpose of this study was to obtain evidence for the utility of NHF as respiratory support for dental treatment under procedural sedation, assessed by determining if the incidence rates of hypercapnia and hypoxemia can be decreased by NHF.

Trial status: The protocol version number and date: Version 1.2 (approved on January 14, 2025). The date recruitment began: Patient recruitment began on August 1, 2025. The approximate date when recruitment will be completed: The patient recruitment will be completed on March 31, 2026.

Background: Slow-wave activity (0.5-4 Hz electroencephalographic activity) during non-rapid eye movement sleep is consistently associated with better cognitive performance in older adults. Slow-wave activity is known to regulate synaptic plasticity and may thereby mitigate excitotoxicity and accumulation of Alzheimer's pathology. Paradoxically, longer total sleep times in older adults are often associated with poorer cognition and general health. Conventional behavioral sleep treatments robustly increase sleep efficiency and sleep time, but do not consistently enhance slow-wave activity and have shown only subtle effects on cognition. Thus, enhancement of slow-wave activity may be a critical target for sleep-based cognitive enhancement. The Alzheimer's Pathways Sleep Study (ALPS) uses a novel time-in-bed (TiB) restriction intervention designed to increase slow-wave activity through homeostatic sleep drive and assesses improvements in measures of excitotoxic hippocampal hyperactivation, plasma levels of amyloid beta (Aβ), and overnight memory retention.

Methods: ALPS is a randomized controlled trial designed to increase slow-wave activity behaviorally in older adults with poor sleep. Target enrollment is 116 participants aged 65-85. Participants are randomized to a TiB restriction intervention or an attention-matched control intervention. Participants randomized to TiB restriction follow a sleep schedule restricting their TiB to 85% of their habitual TiB for 4 weeks. The control group follows their habitual TiB for 4 weeks. Both groups are monitored with diary, actigraphy, check-in calls, and sleepiness ratings over the 4 weeks. The primary outcomes for four specific aims are (1) absolute power in the slow oscillation (0.5-1 Hz) range during non-rapid eye movement sleep, (2) hippocampal activation during memory encoding, (3) plasma Aβ_1-42, and (4) overnight word pair memory retention. Here we describe how the ALPS intervention is administered, the protocols and scripts implemented to maximize adherence and safety, and outcomes measured to test the proposed conceptual model linking slow-wave activity with excitotoxic hyperactivation, Alzheimer's pathophysiology, and memory performance.

Discussion: Behavioral enhancement of homeostatic sleep drive through TiB restriction is a promising approach to improve memory performance and Alzheimer's pathophysiology. Safety measures, as described here, should be implemented to minimize risks associated with TiB restriction.

Trial registration: ClinicalTrials.gov NCT05138848. Registered on December 1, 2021.

There is a growing focus on ensuring research is accessible and inclusive to individuals traditionally not represented. To be truly inclusive, the broader context needs to be explored, as barriers might not only be linked to population characteristics but also to the complexity of their environment, and limited research opportunity within certain healthcare professions. The SCHEMA trial is a randomised controlled trial evaluating whether interpersonal art psychotherapy is effective at reducing aggressive behaviour in individuals with learning disability or borderline intellectual function in secure care. The trial illustrates the challenges and solutions to conducting research in secure care settings, a challenging environment, with an underrepresented patient population and healthcare professionals unfamiliar with conducting research. To better understand the challenges, a survey was circulated to understand site staff's general experience with research and their specific experiences of the SCHEMA trial. Difficulty of balancing research with other responsibilities and a fear of making a mistake were the most common barriers. The top two facilitators were working with collaborators and the presence of clear guidelines and protocols. Site setup was identified as the most challenging stage of the trial, while follow-up data collection was identified as the least challenging. In response to these challenges, the central trial team worked closely with site staff to provide tailored support to address the unique needs of the healthcare professionals and participant population.

Background: Trials have demonstrated that azithromycin mass drug administration (MDA) to children 1-59 months old reduces mortality but increases antimicrobial resistance (AMR). The World Health Organization recommends that programs include mortality and AMR monitoring. Niger is expanding the azithromycin MDA for child survival program nationwide.

Methods: To establish program monitoring and leverage the infrastructure to evaluate other community health interventions, AVENIR II is designed as a cluster-randomized adaptive platform trial with monitoring and re-randomization every 2 years. The initial focus is to monitor under-5 mortality, AMR, implementation, and safety as the azithromycin program expands in Niger. All eligible primary health center catchment areas (Centre de Santé Intégrés, CSIs) will be included in biannual oral azithromycin MDA to children 1-59 months old. A subset will be randomized to delay MDA for the first 2 years, after which they will receive MDA. Another subset will then be randomized to stop MDA for the next 2 years. The proportion randomized to delay or stop will be determined using an adaptive algorithm including (1) results of prior azithromycin MDA mortality trials, (2) expert opinion on the appropriate ethical balance between delivering the program and monitoring AMR, and (3) statistical power to detect a programmatically relevant difference between arms. We anticipate 5-10% of CSIs will be randomized to delay or stop at each randomization. Mortality and AMR will be monitored at baseline and every 2 years. Implementation and safety outcomes will be monitored continuously. To enable ongoing monitoring while ensuring program access, CSIs receiving MDA will be re-randomized using the adaptive algorithm updated with new mortality results, and no CSI will go without MDA for more than 2 years. In this platform design, additional arms may be added or dropped based on information from other studies, updates to guidelines, or preferences of Niger policymakers, and other interventions may be evaluated.

Discussion: The risk of AMR has led to caution in the implementation of azithromycin MDA. We present a design that enables continued rigorous evaluation of program impact on key outcomes, with flexibility to evaluate other interventions as well.

Trial registration: ClinicalTrials.gov NCT06358872. Registered on April 2024.