Trials最新文献

As the fastest growing demographic worldwide, the elderly population is projected to reach nearly 1 billion by 2030 and double the 2022 number by 2050. Despite being the largest consumers of medications, they have been historically underrepresented in clinical trials. However, we are witnessing a promising shift as their participation in trials is on the rise. In fact, recent megatrials enrolling more than 30,000 elderly participants demonstrated the feasibility of large-scale clinical trials involving this very specific population. However, unique challenges, including multi-morbidities, frailty, and ethically sound informed consent in those with cognitive deficits, require continuous careful reassessments and flexibility. Creative and tailored strategies are of paramount importance to bolster elderly trial participation. This paper highlights challenges and shares our experiences on novel methods and success stories associated with the enrollment and retention of elderly individuals in clinical trials. Successful tactics to balance the burden of clinical trial participation with its benefits encompass regular contact, family and friends' engagement, making travel easier or unnecessary, use of digital tools, and building relationships with community organizations. Through innovative strategies that consider the unique needs and limitations of this population, we can achieve successful participation in clinical trials. This will lead to more effective treatments and interventions for our growing elderly population.

Background: The euglycemic clamp test stands as the best method for assessing the pharmacokinetic and pharmacodynamic properties of long-acting insulin. However, despite its widespread use, there remains a notable absence of an established gold standard for evaluating the test's quality. Existing recommendations from regulatory agencies lack specific threshold values, particularly concerning long-acting insulin. This study aimed to determine the evaluation criteria for assessing the quality of the long-acting insulin euglycemic glucose clamp test and to improve the overall quality of this testing method.

Methods: Fifty-three healthy volunteers were administered a single dose of insulin degludec (0.4 IU/kg) and underwent a 24-h euglycemic clamp test. Blood samples were collected to evaluate the pharmacokinetics and pharmacodynamics of insulin degludec. Volunteers were separated into group A (coefficient of variation in blood glucose [CVBG] ≤ 3.5%) and group B (CVBG > 3.5%). The quality difference of the clamp test between the groups was assessed using various quality control indices. Volunteers were also categorized into group C (C-peptide reduction rate < 50%) and group D (C-peptide reduction rate ≥ 50%). The clamp test quality, pharmacokinetics, and pharmacodynamics of groups C and D were compared.

Results: According to CVBG, group A had a mean CVBG of 2.95%, group B had a mean CVBG of 4.15%, and group A had a significantly lower CVBG than group B (p < 0.001). CVBG was positively correlated with other quality control indicators, such as the percentage of glucose excursion from the target range (GEFTR), duration of GEFTR, and area under the curve (AUC) of GEFTR. According to the reduction of C-peptide levels: group D had significantly higher C-peptide reduction than group C (p < 0.001). Groups C and D had CVBG < 3.5%. The quality of groups C and groups D was evaluated by the quality control indicators of the clamp test. Only the AUC of GEFTR was statistically different between Groups C and D (p = 0.043, < 0.05), and there was no statistical difference in other indicators between the two groups.

Conclusions: CVBG could be used as a standard for evaluating the quality of long-acting insulin euglycemic glucose clamp test, and the test quality was superior with a CVBG ≤ 3.5%. A C-peptide reduction ratio ≥ 50% indicated sufficient endogenous insulin inhibition; however, when the glucose fluctuation is small (CVBG is maintained at a low level) during the clamp test, even if the clamp test quality is slightly different, it is not sufficient to interfere with endogenous insulin secretion.

Objective: To evaluate the impact of vitamin E supplementation on sperm analysis results in patients post-varicocelectomy.

Martials and method: This single-center, triple-blind, randomized controlled trial was conducted at Imam Reza Hospital, Mashhad, Iran. Ninety male patients, aged 15-25 years, with infertility and varicocele grade 2 or 3, were randomized into two groups. The intervention group received 400 units of vitamin E daily for 3 months, while the control group received a placebo. Sperm analysis was conducted before and 3 months after the intervention. Statistical analyses were performed using SPSS version 23, with significance set at P < 0.05.

Results: A total of 90 patients were enrolled and equally randomized into two groups (n = 45 per group). The mean age was 30.68 ± 6.31 years. Post-intervention, the improvement in sperm motility was significantly higher in the vitamin E group compared to the placebo group (P = 0.03). Both groups showed significant improvements in sperm motility, count, and morphology from pre- to post-intervention (P < 0.001).

Conclusion: Vitamin E supplementation post-varicocelectomy is associated with improved sperm parameters, suggesting potential benefits in the management of male infertility related to varicocele. However, varicocelectomy alone also results in significant improvements.

Trial registration: This study is registered at the Iranian Registry of Clinical Trials (IRCT20200911048689N1). Registered on October 10, 2020.

Background: Linking registered clinical trials with their published results continues to be a challenge. A variety of natural language processing (NLP)-based and machine learning-based models have been developed to assist users in identifying these connections. To date, however, no system has attempted to detect mentions of registry numbers within the full-text of articles.

Methods: Articles from the PubMed Central full-text Open Access dataset were scanned for mentions of ClinicalTrials.gov and international clinical trial registry identifiers. We analyzed the distribution of trial registry numbers within sections of the articles and characterized their publication type indexing and other metrics.

Results: Registry numbers mentioned in article metadata (e.g., the abstract) or in the Methods section of full-text are highly predictive of clinical trial articles. When a clinical trial article mentioned ClinicalTrials.gov identifier numbers (NCT) only in the Methods section, in every case examined, it was reporting clinical outcomes from that registered trial, and thus can reliably be used to link that trial to that publication. Conversely, registry numbers mentioned in Tables arise almost entirely from reviews (including systematic reviews and meta-analyses). Registry numbers mentioned in other full-text sections have relatively little predictive value for linking trials to their publications. Clinical trial articles that mention CONSORT or SPIRIT guidelines have a higher rate of mentioning registry numbers in article metadata, and hence are more easily linked to their underlying trials, than articles overall.

Conclusions: The appearance and location of trial registry numbers within the full-text of biomedical articles provide valuable features for connecting clinical trials to their publications. They also potentially provide information to assist automated tools in assigning publication types to articles.

Background: Self-stigma refers to the process whereby individuals with mental disorders internalize negative societal attitudes and misconceptions about mental health conditions, potentially affecting their sense of self-worth and identity. This internalization can significantly impact various aspects of life, including treatment engagement, personal relationships, and overall well-being. Narrative Enhancement and Cognitive Therapy (NECT) was developed in the United States to counteract self-stigma and has been supported by multiple randomized controlled trials. However, NECT has not yet been implemented in Italy or within a public mental health system grounded in community psychiatry. This study aims to evaluate the efficacy and feasibility of the Italian version of the NECT within the public mental health sector in a large part of North-East Italy.

Methods and analysis: This pragmatic, multisite, superiority, randomized, wait-list controlled trial with two parallel arms will recruit over four hundred patients with severe mental disorders from 26 public community-based mental health centers in North-East Italy. The experimental intervention, NECT, consists of 20 group-based sessions to reduce self-stigma. The study will assess NECT's impact on several psychological dimensions, including self-stigma levels (primary outcome), self-esteem, hope, empowerment, recovery perception, mental well-being, and stigma stress (secondary outcomes). Feasibility will be evaluated by collecting data on participant adherence and treatment implementation, including eligibility screening, participation rates, intervention completion, exposure levels, and reasons for dropout.

Discussion: The findings of this research are expected to contribute to the understanding of effective treatments for patients with mental disorders, particularly those burdened by high levels of self-stigma, and to improve their recovery outcomes.

Trial registration: ClinicalTrials.gov; Identifier: NCT06567145.

Background: Thoracic aortic pathologies involving the aortic arch are a great challenge for vascular surgeons. Maintaining the patency of supra-aortic branches while excluding the aortic lesion remains difficult. Thoracic EndoVascular Aortic Repair (TEVAR) with fenestrations provides a feasible and effective approach for this type of disease. The main purpose of this trial is to assess the safety and validity of extracorporeal fenestration and in situ fenestration in patients with aortic disease involving the left subclavian artery.

Methods: This is a prospective, single-center, randomized controlled study. A total of 170 eligible patients will be recruited from The Fourth Affiliated Hospital, Zhejiang University School of Medicine in China and randomized on a 1:1 basis either to the group A (extracorporeal fenestration) or the group B (in situ fenestration). The primary outcome will be the all-cause mortality (30 days). The secondary outcomes will include incidence of secondary intervention (30 days, 6 months, 1 year), incidence of endoleak (30 days, 6 months, 1 year), incidence of major adverse events (MAE) (i.e., immediate procedural success and complications) (30 days, 6 months, 1 year), immediate technical success rate, and all-cause mortality (6 months, 1 year).

Discussion: Suppose extracorporeal fenestration non-inferior to in situ fenestration in patients with aortic disease involving the left subclavian artery. This trial aims to demonstrate the safety and validity of extracorporeal fenestration and in situ fenestration in patients with aortic disease involving the left subclavian artery, which is expected to provide a reference for Thoracic EndoVascular Aortic Repair (TEVAR) with fenestrations.

Trial registration: ClinicalTrials.gov NCT06256757. Registered on February 5, 2024. https://clinicaltrials.gov/study/NCT06256757 .

Background: The aim of the SURECAN trial is to evaluate a person-centred intervention, based on Acceptance and Commitment Therapy (ACT Plus ( +)), for people who have completed treatment for cancer with curative intent, but are experiencing poor quality of life. We present the statistical analysis plan for assessing the effectiveness and cost-effectiveness of the intervention in improving quality of life 1 year post randomisation.

Methods and design: SURECAN is a multi-centre, pragmatic, two-arm, partially clustered randomised controlled superiority trial comparing the effectiveness of ACT + added to usual care with usual aftercare. The target sample size is 344 (172 per arm), randomised centrally in a 1:1 ratio.

Results: The primary outcome is the total score of the Functional Assessment of Cancer Therapy scale-General (FACT-G) at 52 weeks, analysed using a partially nested mixed-effects model with heteroskedastic error terms. Secondary outcomes include scores at 16 and 52 weeks: FACT-G subscales; Fear of Cancer Recurrence Inventory (FCR4); positive and negative Impact of Cancer scales (IOCv2); Hospital Anxiety and Depression scale (HADS); Chalder Fatigue Scale (CFQ); and physical activity, measured on a modified version of the Godin scale. Health economic analyses will determine the incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life years (QALYs) derived from the Euroqol 5-Dimension 5-Level (EQ-5D-5L) compared to usual care at 52 weeks.

Discussion: This manuscript is the statistical analysis plan (SAP) and economic evaluation for the SURECAN trial. Any exploratory or post hoc analyses will be identified as such in the respective analysis report.

Trial registration: The trial was prospectively registered.

Isrctn: ISRCTN67900293. Registered on 09 December 2019.

Background: /aims. Pseudoxanthoma Elasticum (PXE, OMIM 264800) is an autosomal, recessive, metabolic disorder characterized by progressive ectopic calcification in the skin, the vasculature and Bruch's membrane. Variants in the ABCC6 gene are associated with low plasma pyrophosphate (PPi) concentration. There is currently no reference treatment for this chronic debilitating disease.

Methods: PROPHECI (PyROphosPHate supplementation to fight ECtopIc calcification in PseudoXanthoma Elasticum) is the first phase II, randomized, double-blind, placebo-controlled clinical trial (NTC 04868578) to evaluate the efficacy and safety of a daily oral PPi salt supplementation to attenuate and/or stabilize the progression of ectopic calcification in PXE patients. The primary endpoint is the change in arterial calcification volume quantified by non-contrast CT scan between baseline and 12 months of treatment. Secondary endpoints include the safety and efficacy of daily oral PPi administration on ocular and skin lesions and the evaluation of patients' quality of life.

Discussion: The PROPHECI trial aims to provide safety and efficacy data on the use of daily oral PPi to reduce or stabilize ectopic calcification in PXE. It also aims to validate the best markers to include in the design of future trials for the treatment of PXE and other parent diseases.

Trial registration: Trial registration number: NCT04868578. References can be found on the ClinicalTrials.gov website: https://clinicaltrials.gov/study/NCT04868578?cond=Pseudoxanthoma%20Elasticum&intr=pyrophosphate&rank=2.

Background: Women's football has experienced exponential growth over the last 10 years. Its popularity is associated with an increase in ACL injuries. They constitute a major current problem as they account for 43% of the injury burden during the sports season. Despite the existing training programs, no uniform criteria have been established to design a precise intervention protocol, with specific tasks linked to women's football, nor has it been proposed to optimize the current programs.

Methods: Randomized, double-blind, single-center clinical trial protocol scheduled for the 2025-2026 women's football season. There will be 2 groups: a group that will follow a specific ACL injury prevention protocol and a control group. The intervention period will last 12 weeks. Measurements will be taken at 3 time points. The biomechanics of the lower limbs, the jump-landing dynamics, and the pre- and post-training satisfaction of the players will be evaluated. Image capture and processing systems will be used as well as tests such as the DVJ and the LESS scoring system, among others.

Discussion: This protocol aims to be one of the first to implement an ACL injury prevention program for women footballers with DKV. Despite the scarcity of research in this area, studies support beneficial effects at a preventive level.

Trial registration: ClinicalTrials.gov NCT06083818. Registered on 03 October 2023.

Background: Phase-3 clinical trials provide the highest level of evidence on drug safety and effectiveness needed for market approval by implementing large randomized controlled trials (RCTs). However, 30-40% of these trials fail mainly because such studies have inadequate sample sizes, stemming from the inability to obtain accurate initial estimates of average treatment effect parameters.

Methods: To remove this obstacle from the drug development cycle, we present a new algorithm called Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator (TAD-SIE) that powers a parallel-group trial, a standard RCT design, by leveraging a state-of-the-art hypothesis testing strategy and a novel trend-adaptive design (TAD). Specifically, TAD-SIE uses synthetic intervention (SI) to estimate individual treatment effects and thereby simulate a cross-over design, which makes it easier for a trial to reach target power within trial constraints (e.g., sample size limits). To estimate sample sizes, TAD-SIE implements a new TAD tailored to SI given that using it violates assumptions under standard TADs. In addition, our TAD overcomes the ineffectiveness of standard TADs by allowing sample sizes to be increased across iterations without any condition while controlling significance level with futility stopping. Our TAD also introduces a hyperparameter that enables trial designers to trade off between accuracy and efficiency (sample size and number of iterations) of the solution.

Results: On a real-world Phase-3 clinical RCT (i.e., a two-arm parallel-group superiority trial with an equal number of subjects per arm), TAD-SIE obtains operating points ranging between 63% to 84% power and 3% to 6% significance level in contrast to baseline algorithms that get at best 49% power and 6% significance level.

Conclusion: TAD-SIE is a superior TAD that can be used to reach typical target operating points but only for trials with rapidly measurable primary outcomes due to its sequential nature. The framework is useful to practitioners interested in leveraging the SI algorithm for their study design.