Contemporary Clinical Trials Communications最新文献

Background

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, those with severe COVID-19 infection were at risk for a number of opportunistic infections including COVID-19-associated pulmonary aspergillosis (CAPA). We initiated a randomized clinical trial to evaluate whether isavuconazole, a triazole antifungal, could prevent CAPA and improve survival in patients admitted to the ICU with severe COVID-19 infection.

Methods

We designed a phase III/IV randomized, double-blind, two-arm, placebo-controlled trial evaluating standard of care (SOC) plus isavuconazole versus SOC plus placebo and were to enroll participants admitted to the ICU with severe COVID-19 infection at three medical centers in California, United States. The projected sample size was 162 participants.

Results

Due to poor enrollment and the declining number of COVID-19 cases over time, the study was terminated after 7 participants were enrolled, all enrolled at one study site (UC San Diego Health). CAPA was suspected in two participants and they were started on open-label isavuconazole. One was withdrawn due to possible isavuconazole-related adverse side effects.

Conclusion

Enrollment was slower-than-expected due to multiple factors, including competing COVID-19-related studies and hesitancy from potential study participants or their families to join the study. Our experience highlights some of the difficulties in planning and running a clinical trial focused on fungal superinfections involving severely ill patients during the height of the COVID-19 pandemic. Lessons learned from this study will help in the design of proposed studies examining antifungal prophylaxis against aspergillosis following other severe respiratory viral infections.

The use of e-cigarettes (“vaping”) by young adults has increased substantially in the past decade. Although health risks of long-term e-cigarette use remain unknown, there is evidence of acute physiological harms. Most young adults who vape report intent to quit, but little is known about effective interventions. This protocol paper reports on the development and design of a pilot trial of a vaping intervention for young military Veterans.

Young adult Veterans accessing VA healthcare (n = 20) who vape daily and have been referred for cessation services will be enrolled. To maximize accessibility the intervention will be delivered virtually; participants will be randomized to receive behavioral counseling by telephone or by video telehealth. The intervention was adapted from an existing program targeting young adult cigarette smokers and will include 6 individual counseling sessions delivered over 8 weeks. Assessment visits will occur at baseline, at end-of-treatment, and 4 weeks later.

Analyses will evaluate feasibility and acceptability of the intervention overall, and will compare telephone and video telehealth modalities. Longitudinal regression will be used to evaluate changes in vaping behavior and in nicotine dependence over time.

This study will provide assessment of a novel intervention adapted for Veterans who vape nicotine. The comparison of two modalities of virtual intervention delivery will increase knowledge and the potential to disseminate across VA and other healthcare systems. Findings from this pilot trial will inform the design of future, larger studies of vaping cessation interventions for younger Veterans.

Introduction

Uncertainty regarding the timing of weight bearing following ankle open reduction internal fixation (ORIF) in patients with different ankle fracture patterns remains. Traditional rehabilitation methods, including six weeks of non-weight bearing (NWB), is still a common approach in many hospitals, while some previous evidence has shown immediate weight bearing (IWB) to be beneficial.

Method

32 adult participants with unimalleolar, bimalleolar or trimalleolar ankle fractures and stable fixation following ankle ORIF will be randomly allocated to either Immediate Weight Bearing (IWB) or Delayed Weight Bearing (DWB) groups. Stability of fixation is a subjective assessment made by the operating surgeon at the completion of fixation and is independent of fracture pattern. Participants in the IWB group will be allowed to weight bear as tolerated within 24 h, while participants in the DWB group will remain non-weight bearing for six weeks. Participants’ data including Olerud and Molander Ankle Score, Self-Reported Foot and Ankle Score, SF-36 health survey, time to return to work will be collected. X-rays will be assessed by orthopaedic team members for fixation-related complications including reduction loss, malreduction/malunion, implant failure and non-union. Participants data will be collected at six weeks, three and six-months post-surgery. We will determine the feasibility of a full RCT through assessing the recruitment rate, adherence rate, and drop-out rate.

Results

Not applicable.

This pilot RCT will endeavour to optimise standard rehabilitation protocols post ankle ORIF.

Randomized clinical trials are the gold standard for clinical trials as they reduce bias and minimize variability between different arms of a study. One of the drawbacks of these designs is their lack of flexibility to incorporate participant’s treatment choice, which may reduce recruitment rates and/or reduce participant’s tolerance if they receive a non-preferred treatment. Designs incorporating choice allow a subset of participants to choose their preferred treatment. Most of the current methods to analyze these types of designs are based on an ANOVA approach that do not allow for inclusion of covariates in the model. In this paper, we propose an alternative approach based on likelihood methods that can be used with a broad class of distributions and allow for inclusion of covariates and multiple study arms in the model. Using simulations, we evaluate these methods for a variety of continuous and categorical outcomes. Finally, we illustrate these methods by analyzing change in six minute walking distance from a behavioral intervention study for women with heart disease.

Background

Growing evidence suggests that increasing opportunities for social engagement has the potential to support successful aging. However, many older adults may have limited access to in-person social engagement opportunities due to barriers such as transportation. We outline the development, design, methodology, and baseline characteristics of a randomized controlled trial that assessed the benefits of a social engagement intervention delivered through the OneClick video conferencing platform to older adults with varying levels of cognitive functioning.

Methods

Community-dwelling older adults with and without cognitive challenges were randomly assigned to a social engagement intervention group or a waitlist control group. Participants were asked to attend twice-weekly social engagement events for 8 weeks via OneClick. Outcomes included social engagement and technology acceptance for both groups at baseline, week-4, and week-8 assessments. As an extension, the waitlist control group had an opportunity to participate in the intervention, with outcomes assessed at weeks 12 and 16.

Results

We randomly assigned 99 participants (mean age = 74.1 ± 6.7, range: 60–99), with 50 in the immediate intervention group and 49 in the waitlist control group. About half of the participants reported living alone (53.5%), with a third (31%) falling into the cognitively impaired range on global cognitive screening. The groups did not differ at baseline on any of the outcome measures.

Conclusions

Outcomes from this study will provide important information regarding the feasibility and efficacy of providing technology-based social engagement interventions to older adults with a range of cognitive abilities.

Background

The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with acute medical conditions. The registry-based randomized DAPA-MI clinical trial recruited patients during hospitalization for myocardial infarction and provided study drugs in bottles with smart caps that used wireless technology to transmit monitoring data. This interview study aimed to investigate patients’ experience of participation in a clinical trial and their attitude to the new bottle cap technology.

Methods

A subset of patients participating in the DAPA-MI trial were recruited from four hospitals in Sweden. Semi-structured interviews were conducted and analysed using manifest content analysis.

Results

Video interviews were performed including 21 patients (four women and 17 men). The median age was 59 years (range 44–80). Four categories of patients' experiences were identified. A willingness to contribute consisted of patients’ positive attitudes to participation and to be a part of development and research. The perception of information emphasized the value of the oral information as well as the importance of time for reflection. Be in a vulnerable condition highlighted the impaired ability to perceive and remember in the acute medical condition. Adaptation to a new technology described the overall positive experiences of the smart bottle cap to evaluate adherence.

Conclusions

Patients’ experiences of trial participation were in general positive but some challenges in the acute setting of a myocardial infarction were revealed. The smart bottle cap was well accepted, despite some handling difficulties.

Background

Incidental findings (IFs) in radiographic imaging are unexpected discoveries unrelated to the purpose of the scan. While the protocol for communicating IFs is better defined for clinical providers, little formal guidance on communicating IFs identified on research scans to participants is available. This study explored participants’ experience with communication and management of IFs found on imaging identified in a clinical research trial.

Methods

Participants who completed the parent clinical trial, which included imaging, were invited to participate. A survey, developed by the study team, was administered telephonically, and consisted of multiple choice and open-ended questions.

Results

Thirty participants enrolled in the survey study. Ninety-three percent of all participants (with and without IFs) reported they would participate in another research study to learn information that was important to their health. Seventeen participants reported being notified about an IF on their study scan(s). Ninety-four percent of those participants with an IF were satisfied with how the IF was communicated, and 71 % were grateful to find out about a health problem before it became an issue. Forty-one percent reported that learning about the IF led to improved health. Content analysis of the data from the open-ended questions revealed categories and themes which enriched the quantitative data.

Conclusion

Participants generally wanted to know when an IF was discovered unexpectedly on their imaging scan, as they learned important information about their health. Findings underscore the importance of having a clear protocol for communicating IFs to research study participants that undergo evaluation with radiographic imaging.

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10–15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients.

There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

Levels of the male sex hormone testosterone are generally stable in the age interval 20–70 years, but several studies indicate an earlier, age-dependent decline. Testosterone deficiency is often underdiagnosed and under-treated, but replacement therapy has nonetheless increased during the last couple of years. Owing to possible negative side effects, alternative treatments have been investigated, including different supplementation protocols. The aim of this study was to investigate the effect of probiotic supplementation on the testosterone level in healthy men aged between 55 and 65. Hence, 12 weeks randomized, double-blinded, placebo-controlled trial was conducted to investigate the effect on testosterone levels following supplementation of the recognized probiotic Limosilactobacillus reuteri ATCC PTA 6475 on testosterone levels, using high-, low- or placebo treatment. Venous blood samples were collected at baseline, 6 and 12 weeks, for analysis of bloodwork, lipid profile, hormones, and electrolytes. Subjects were also asked to complete a questionnaire. The supplementation had no effect on testosterone levels, neither using high- or low dose, nor placebo. However, a significant decrease of triglyceride levels was observed in the high-dose group. No other parameters showed any significant change. The present study does not support the hypothesis that a probiotic supplementation can increase testosterone levels in ageing men.

Introduction

Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism.

Methods and analysis

and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment.

Discussion

Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated.

Ethics and dissemination

Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary.

Trial registration

NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023.