Trials最新文献

Introduction: ASCEND assessed the effects of randomisation to aspirin versus placebo and, separately omega-3 fatty acid (FA) supplementation versus placebo on vascular events in 15480 adults with diabetes using mail-based remote methods. This analysis investigates factors associated with adherence to the allocated treatments.

Methods: Adherence was estimated from the 6-monthly follow-up forms and the supply of study treatment packs. A binary adherence variable, full versus less than full adherence during the period at risk of a serious vascular event (SVE), was investigated using logistic regression. Potential predictors of adherence considered were sex, age at randomisation, Hospital Frailty Risk Score, ethnicity, Townsend index, smoking status, type of diabetes, predicted 5-year vascular risk, number of other medications reported at study entry and treatment allocation.

Results: Seven thousand, three hundred twelve (47.2%) participants were fully adherent to aspirin/placebo and 8937 (57.7%) were fully adherent to omega-3 FA/placebo while at risk of a SVE. Women were less likely to be fully adherent than men (aspirin randomisation: 2509 [43.3%] vs. 4803 [49.6%]; OR, 0.73; 95% CI: 0.68 to 0.80; P < 0.0001; omega-3 FA randomisation: 3035 [52.4%] vs. 5902 [61.0%]; OR, 0.67; 95% CI: 0.61 to 0.72; P < 0.0001) and adherence decreased with increasing frailty (trend p-value < 0.0001), smoking (p-value < 0.0001), vascular risk score (p-value < 0.0001) and deprivation (trend p-value = 0.0211, p = 0.0011).

Conclusion: We show this large, mail-based trial has comparable adherence with less streamlined trials in similar populations. In ASCEND, women and those with higher levels of frailty, smoking and vascular risk score had poorer adherence to trial medication. Trialists should consider strategies to improve adherence in these participant groups.

Background: Newer oxazolidinones will be required to advance regimens in pan-TB indications. The addition of host-directed agents may help promote the recovery of lung function during TB treatment and prevent post-TB lung disease.

Methods: The panTB-HM trial assesses the capacity of three novel regimens containing the oxazolidinone sutezolid and the antioxidant N-acetylcysteine (NAC) to meet the target criteria proposed by WHO for pan-TB indications (including use without rifamycin susceptibility testing and of 4 months or less duration) in a phase 2C trial.

Discussion: This trial is ground-breaking in its objectives and design for a 4-month pan-TB indication (in a non-inferiority comparison to standard treatment) and its evaluation of lung function recovery (in a superiority comparison).

Trial registration: ClinicalTrials.gov NCT05686356. Registered on 13 Jan 2023.

Background: Accurate and rapid diagnosis of early-onset neonatal sepsis (EOS) in preterm infants remains problematic due to a lack of specific symptoms and diagnostic tools. Following the Dutch EOS guidelines, over 80% of infants born < 32 weeks of gestation are empirically started on antibiotics directly after birth, while the actual incidence of EOS varies between 1 and 2%. Unnecessary antibiotic exposure leads to severe short and long-term complications. The biomarker presepsin, also known as soluble CD14 subtype, may be used to reduce antibiotic prescription in preterm infants after birth. The objective of this study is to investigate whether adding a presepsin-guided decision to the guideline safely reduces antibiotic exposure directly after birth in preterm infants. Secondly, the diagnostic accuracy of presepsin for EOS will be evaluated.

Methods: The PRESAFE trial is a multicentre, randomized controlled trial (RCT), including a concurrent observational study. Presepsin levels are determined from umbilical cord blood or during the first regular blood draw in all infants born < 32 weeks gestation. Infants who qualify for empirical antibiotics according to the Dutch EOS guideline are categorized as moderate or high risk for EOS based on prespecified high-risk criteria. Infants not qualifying for empirical antibiotics are categorized as low risk. Preterm infants with a moderate risk for EOS are randomized 1:1 into an intervention arm and a comparator arm. In infants allocated to the intervention arm, empirical antibiotics will only be started above a prespecified presepsin level of ≥ 645 pg/ml. In the comparator arm, infants will be treated according to the standard of care following the Dutch EOS guideline, equivalent to starting empirical antibiotics. The co-primary outcomes of the RCT are the incidence of culture-proven EOS (non-inferiority) and unnecessary antibiotics administration (superiority). The required sample size for the RCT is 900 patients. Infants with a high- or low-risk of EOS are excluded from randomization but included in a concurrent observational study and treated according to the Dutch EOS guideline. The primary outcome of this part is the diagnostic accuracy of presepsin.

Discussion: The findings of the RCT will provide evidence for safe and effective reduction of administration of antibiotics for suspected EOS in infants born < 32 weeks of gestation. The observational study will provide more insight in the diagnostic accuracy of all infants born < 32 weeks of gestation.

Trial registration: ClinicalTrials.gov NCT06100614. First registered on October 25, 2023.

Background: Among adolescents, internalizing disorders are a leading cause of the global burden of disability and death due to suicide. There is a critical need to prevent first-lifetime onsets of internalizing disorders, particularly among high-risk adolescents. Insomnia and poor sleep have been robustly linked to internalizing disorders in adolescents. The present trial will examine if brief, web-based Cognitive Behavioral Therapy for Insomnia (CBT-I) reduces insomnia symptoms, improves sleep quality, and improves subthreshold internalizing symptoms in never-clinically depressed or anxious adolescents with sleep problems (insomnia severity scores indicating subthreshold insomnia or higher) who are at risk for internalizing disorders due to a parental history of these disorders.

Methods: This trial uses a two-arm, single-blinded, parallel group randomized controlled design (N = 50). Participants in the treatment group will complete a web-based CBT-I intervention (return2sleep) that is comprised of 7 sessions (six adolescent sessions and one parent session). Participants in the control group will receive a psychoeducational pamphlet and be encouraged to continue treatment (if any) as usual. Insomnia severity, sleep quality, and depressive and anxiety symptoms will be assessed at three time points (baseline, immediately post-treatment, and three months post-treatment). Additionally, clinically significant internalizing disorders in adolescents will be assessed using diagnostic interviews.

Discussion: Web-based CBT-I is a non-invasive, economical, and easily administered intervention targeting sleep which is a potentially modifiable risk factor for the onset of depression and anxiety. Results from this trial will inform larger-scale effectiveness trials to examine whether, via interventions to improve sleep, it is possible to prevent currently healthy, but high-risk, adolescents with sleep problems from developing internalizing disorders for the first time in their lives, thereby preventing a lifelong cascade of adverse psychosocial outcomes.

Trial registration: ClinicalTrials.gov NCT06358495. Registered on April 15, 2024.

Background and aims: Cancer-related lymphedema (CRLE), a chronic complication of cancer treatment, affects 39-73% of patients post-lymph node dissection, impacting physical health, social participation, and finances. Prophylactic immediate lymphatic reconstruction (ILR) via lymphaticovenous anastomosis (LVA) has shown potential in reducing CRLE incidence by two-thirds following axillary and inguinal node dissection. However, rigorous phase III studies with long-term follow-up are still needed to confirm these promising results. This study aims to evaluate the efficacy, safety, and long-term outcomes of ILR in preventing CRLE in a prospective, controlled trial setting.

Methods/designs: A phase III randomized controlled trial will evaluate an intervention in adult patients undergoing axillary or groin node dissection for cutaneous malignancy. Block randomization will stratify participants by upper or lower extremities. Primary outcomes include lymphedema incidence and quality-of-life measures. Statistical analyses will compare lymphedema rates and quality-of-life outcomes between intervention and control groups.

Objectives: The primary endpoint is to assess the impact of prophylactic LVA on the presence or absence of lymphedema post axillary or groin lymphadenectomy and participant quality of life. The secondary endpoint is the incidence of complications related to nodal dissection.

Significance: CRLE, a common complication of cancer surgery and radiotherapy, severely impacts patients' lives and healthcare resources. Reducing its incidence by two-thirds would significantly improve outcomes for cancer survivors and decrease treatment demands. This underscores the need for advanced research in prevention and early intervention strategies to mitigate lymphedema's burden on patients and healthcare systems.

Trial registration: ClinicalTrials.gov ID NCT05136079 2021-11-02.

Background: Alzheimer's disease (AD) is the most common degenerative brain disorder leading to dementia, characterized by a slow onset and gradual progression. Early symptoms typically include difficulties in recalling recent events, which later extend to impairments in various cognitive functions such as language, judgment, and problem-solving, ultimately resulting in the complete loss of independent daily functioning. KCHO-1, a herbal extract with demonstrated anti-inflammatory and neuroprotective properties, has shown promise in mitigating the effects of neurodegenerative disorders. This study aims to develop a protocol for determining the optimal dosage of KCHO-1 in treating AD, providing a foundation for its potential therapeutic application.

Methods: This is a phase II, multi-center, 3-arm randomized controlled study. Sixty patients with AD will be randomly assigned to one of three groups. Each group will receive a standard treatment with 1.6 g of KCHO-1, 2.4 g of KCHO-1, or a placebo. The primary outcome is ADAS-K-cog. Secondary outcomes include results of K-MMSE, K-IADL, NPI-Q, CDR, GDS, KQOL-AD, R-MBPC, and S-GDpS. The frequencies of severe adverse events as well as overall adverse occurrences are listed and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Hospital Gwangju Korean Medical Center and Wonkwang University Hospital (WKIRB 2021/14-19 and WKUH IRB 2023-10-005-012, respectively). The Ministry of Food and Drug Safety (MFDS) approved the drug as an investigational new drug (30731).

Discussion: The purpose of this study is to establish the ideal KCHO-1 dosage. Additionally, it seeks to validate KCHO-1's safety and effectiveness in reducing functional deterioration in AD patients.

Trial registration: Korean National Clinical Trial Registry CRIS; KCT0008433. Registered on 12 May 2023.

Background: Periodontal intrabony defects pose significant challenges in periodontal therapy. Traditional surgical approaches often lead to substantial morbidity and high costs. Recently, endoscopic-assisted subgingival debridement (EASD) has emerged as a non-inferior alternative. This study aims to establish the efficacy of the endoscopic-assisted flapless approach to periodontal regeneration compared to periodontal regeneration with the papilla preservation technique (PPT) in managing residual periodontal intrabony defects.

Methods: This single-centre single-blinded randomized controlled clinical trial aims to recruit 56 participants with residual periodontal intrabony defects. Subjects will be randomly assigned to receive either EASD combined with enamel matrix derivatives (EMD) (test therapy) or PPT combined with EMD (control therapy) in a 1-to-1 ratio, delivered by the clinical investigator. Subjects will be followed up to 12 months post-operation, and an independent, blinded assessor will be responsible for collecting clinical, radiographic endpoints, and patient-reported outcomes measures.

Discussion: This study aims to produce information on the efficacy of periodontal regeneration with EMD in combination with EASD or PPT in the management of intrabony periodontal defects. The findings of this study will assess whether the endoscopic-assisted flapless approach is a non-inferior alternative to the PPT approach for periodontal regeneration, offering additional benefits in terms of patient morbidity and operative time.

Trial registration: ClinicalTrials.gov NCT06978036.

Background: Stroke is common, affecting an estimated one in four people in their lifetime. Fortunately, stroke is also highly preventable. With the rise in digital literacy and the increasing adoption of digital health tools, a promising avenue for stroke prevention is through digitally-delivered interventions. Love Your Brain: A stroke prevention digital platform is a three-year research project to develop and evaluate a digital platform to 1) increase participant visits to their medical practitioner for assessment or management of cardiovascular risk factors (primary outcome); and 2) improve participants' health-related stroke knowledge, adherence to prevention medications and uptake of healthy or risk-modifying behaviour (secondary outcomes). The project is a multi-arm randomised controlled trial, comparing the common control arm to each of the intervention arms (either an online course or text messages). We present the statistical analysis plan for this trial.

Methods/design: Participants are randomised 1:1:1 in variable block sizes, with stratification balancing by age and sex. The sample size of 894 participants was calculated to detect a 30% relative intervention effect, with 80% power and 5% significance level (two-sided). Recruitment will end when the sample size is achieved (adjusting for ≤ 10% attrition rate). The primary outcome will be compared separately for each intervention arm with the common control arm. As the outcome is binary, log-binomial regression models will be used with adjustment for stratification variables (i.e., gender, age groups [45-64 and >= 65 years]) and covariates that demonstrate imbalances between arms at baseline. Secondary outcomes will be evaluated using generalised mixed effects regression models (including linear, log-binomial, or quantile regression). The primary outcome analysis will be based on intention-to-treat. A p-value ≤ 0.05 will indicate statistical significance.

Conclusions: This statistical analysis plan ensures transparency in reporting the trial outcomes. Love Your Brain will provide novel evidence on the effectiveness of two digital health education platforms for the prevention of stroke.

Trial registration: ACTRN12625000124437; U1111-1305-2964 Feasibility Pilot: Australian New Zealand Clinical Trials Registry: ACTRN12624000540516; Universal Trial Number: U1111-1305-2964. SAP Version: 1.0 (September 2025) Protocol version: 1.0 (December, 2024) SAP revisions: Nil.

Background: Poststroke cognitive impairment (PSCI) has an incidence rate ranging from 24% to 80.97%. It reduces survival rates and increases disability among stroke patients, posing a substantial socioeconomic burden. Current treatments for PSCI primarily involve medication and rehabilitation; however, therapeutic efficacy remains limited, with unsatisfactory improvement in activities of daily living. This study aims to conduct a prospective clinical trial to evaluate the safety and efficacy of 40-Hz sensory stimulation-induced gamma oscillations in the treatment of PSCI, including assessment of neuropsychology, psychiatric symptoms, cerebral blood perfusion, and functional and structural brain changes, and to investigate the underlying mechanisms by RNA-sequencing of blood samples.

Methods: This trial is designed as a prospective, randomized controlled, double-blind, non-inferiority study conducted in the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine in China. Participants with confirmed cognitive impairment occurring after the stroke event and persisting for 3 to 6 months will be screened and recruited by the attending neurologists for participation. A total of 120 enrolled patients will be randomly assigned to one of two groups at a ratio of 1:1. The experimental group will receive 40-Hz sensory stimulation, while the control group will receive sensory stimulation at random frequencies. Both groups will receive the same standard clinical drug therapy and rehabilitation treatment. The primary efficacy endpoints include cognitive function and learning ability. Secondary endpoints encompass changes in cerebral hemodynamics, neural network connectivity, synaptic-related gene expression, and neurotransmitter levels. Safety assessments will include monitoring of major adverse events, all-cause mortality, and photosensitive epilepsy. Evaluations will be conducted at baseline, after the 14-day treatment period, and during follow-up visits (at 3 and 6 months). Differences between the two groups will be compared.

Discussion: This study will assess the safety and efficacy of gamma oscillations induced by 40-Hz sensory stimulation in treating PSCI patients. In parallel, potential mechanisms-including alterations in synaptic-related genes and neural network connectivity-will be explored. This trial is expected to provide evidence supporting the effectiveness of this novel technique for treating PSCI and improving patients' quality of life.

Trial registration: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2400088535. Registered on 20 August 2024.

Background: Young adults are experiencing rising levels of mental health concerns and low well-being, which is exacerbated for around 20% of the population who are high in sensory processing sensitivity (SPS), a distinguishable, partly heritable trait associated with poorer mental health. However, despite this worrying increase in mental health issues among young adults, individuals who score highly on beauty appreciation tend to enjoy better well-being and improved mental and physical health. Several studies have shown that beauty appreciation can be taught and may serve as a cost-effective and enjoyable intervention strategy that can be easily implemented.

Methods: This study has two main aims: (1) to evaluate the effectiveness of an art-based beauty appreciation intervention on enhancing beauty appreciation (primary outcome), and (2) to determine whether increasing beauty appreciation has a causal effect on reducing psychological distress and increasing mental well-being (secondary outcomes) when compared to an active matched control condition designed to isolate beauty appreciation skill development. To assess this, we will conduct a mixed-method randomised controlled trial (RCT) across three measurement points: enrollment, post-intervention, and a 4-week follow-up. N = 114 young adults, including those high in SPS, will be blinded and randomly allocated to the intervention or control group (~ N = 57/group). Our primary hypothesis is that the intervention condition will exhibit higher levels of beauty appreciation compared to the control group at the post-test while accounting for baseline differences. Our secondary hypotheses address mental well-being and psychological distress. A follow-up analysis will assess if individuals with high SPS can especially benefit and qualitative analysis will address mechanisms, barriers and facilitators between intervention and control, as well as in a high SPS subgroup.

Discussion: The study aims to provide evidence that beauty appreciation skills specifically can lead to increased well-being and decreased psychological distress by including an active matched control condition that isolates this skill development. Based on positive results, the evidence will support the implementation of such interventions for young adults and highly sensitive individuals, which would be widely accessible and easy to incorporate into day-to-day life.

Trial registration: ClinicalTrials.gov Registry Number: NCT06788496 (2024-12-22).