Trials最新文献

Background: Postoperative sore throat (POST) is a common complaint after general anaesthesia. The prevalence of POST caused by a neural integrity monitor electromyography endotracheal tube (NIM-EMG-ETT) is high. This study aimed to determine whether ultrasound-guided internal branch of superior laryngeal nerve block (iSLNB) could alleviate POST associated with a NIM-EMG-ETT.

Methods: This randomized controlled trial plans to enroll 182 patients scheduled to undergo general anaesthesia with a NIM-EMG-ETT. Patients will be randomly allocated into the iSLNB group or the control group according to randomized numbers generated by Excel. After induction, patients in the iSLNB group will undergo ultrasound-guided iSLNB with ropivacaine, and patients in the control group will undergo the same procedure with normal saline. The prevalence, severity, visual analogue scale score of POST, and postoperative acoustic analysis will be recorded.

Discussion: To the best of our knowledge, this is the first study to evaluate the effect of ultrasound-guided iSLNB with ropivacaine on the mitigation of POST induced by NIM-EMG-ETT. Our study will provide clinical answers to alleviate POST induced by NIM-EMG-ETT. The results of this study may provide a safe method to prevent POST caused by NIM-EMG-ETT.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076393. Registered on October 24, 2023, http://www.chictr.org.cn/index.aspx .

Background: Diabetes affects 10.5% of adults globally, with type 2 diabetes accounting for 90-95% of cases. Achieving optimal glycemic control is crucial yet challenging, particularly with insulin therapy, where 30-50% of patients fail to meet treatment targets. Telemedicine can improve diabetes management but generates vast amounts of data, burdening healthcare professionals. Integrating clinical decision support tools into telemonitoring systems may enhance care efficiency and glycemic control.

Methods: The trial is a multicenter 3-month, three-arm, open-label, randomized controlled trial. The trial aims to enroll 51 participants with type 2 diabetes on insulin therapy. Participants will be divided with a 3:1:1 ratio into telemonitoring with decision support, telemonitoring without decision support, and usual care groups. The study employs connected insulin pens, continuous glucose monitors (CGMs), and activity trackers to enable telemonitoring. Outcomes measured include CGM time in range, HbA1c, hypo- and hyperglycemia incidents, total daily insulin dose, body weight, treatment satisfaction, and adherence.

Discussion: Telemonitoring with decision support has the potential to revolutionize diabetes management by offering personalized treatment suggestions, thereby reducing the burden on healthcare professionals, and improving patient outcomes. This study will provide valuable insights into the effectiveness of such an approach in achieving glycemic control in people with type 2 diabetes on insulin therapy. By evaluating both clinical outcomes and patient and healthcare professionals' satisfaction, the study aims to contribute to the development of efficient, scalable telehealth solutions for diabetes care.

Trial registration: ClinicalTrials.gov NCT06185296. Registered on December 14, 2023.

Background: Integration of symptom and palliative care for people with advanced cancer is established in many tumour types, but its role in people with hepatocellular carcinoma (HCC) has not been clearly defined. This study aims to evaluate the clinical and cost effectiveness of an intervention involving a suite of strategies designed to assess and treat palliative care symptoms and needs in adult outpatients with HCC attending four New South Wales (NSW) metropolitan tertiary hospitals.

Methods: This trial will use a pragmatic cluster-based randomised-controlled design, with ambulatory HCC services as the clusters. HCC patients will be recruited if they have Barcelona Clinical Liver Cancer (BCLC) stage A disease with active tumour or a current or prior diagnosis of BCLC stage B or C disease regardless of tumour activity. Patients with BCLC stage D disease will be excluded as palliative care is the standard of care (SOC) in this group. Cluster sites will be randomised to the study intervention or control where patients are managed according to SOC. All participants will complete the liver-specific Edmonton Symptom Assessment Scale (ESAS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at regular ambulatory clinic appointments. At intervention sites, patients scoring ≥ 5 on any liver-specific ESAS symptom will be referred to palliative care physicians for consultation. The primary clinical outcome will be improvement in all symptoms scored ≥ 5 on the liver-specific ESAS by 50% within 3 months and the primary implementation outcome will recording the liver-specific ESAS in ≥ 80% of all participants attending clinic appointments. Caregivers of patients enrolled in the trial will be invited to perform Carer Support Needs Assessment Tool at each appointment.

Discussion: This trial will inform if earlier palliative care involvement significantly reduces the symptom burden associated with HCC. If found to be effective, earlier implementation of palliative care consultation should be included in HCC treatment guidelines.

Trial registration: ACTRN12623000010695. Registered on September 1, 2023.

Background: The NOTACS trial will assess the efficacy, safety and cost-effectiveness of high-flow nasal therapy (HFNT) compared to standard oxygen therapy (SOT) on the outcomes of patients after cardiac surgery.

Methods/design: NOTACS is an adaptive, international, multicentre, parallel group, randomised controlled trial, with a pre-planned interim sample size re-estimation (SSR). A minimum of 850 patients will be randomised 1:1 to receive either HFNT or SOT. The primary outcome is days alive and at home in the first 90 days after the planned surgery (DAH90), with a number of secondary analyses and cost-effectiveness analyses also planned. The interim SSR will take place after a minimum of 300 patients have been followed up for 90 days and will allow for the sample size to increase up to a maximum of 1280 patients.

Results: This manuscript provides detailed descriptions of the design of the NOTACS trial and the analyses to be undertaken at the interim and final analyses. The main purpose of the interim analysis is to assess safety and to perform a sample size re-estimation. The main purpose of the final analysis is to examine the safety, efficacy and cost-effectiveness of HFNT compared to SOT on the outcomes of patients after cardiac surgery.

Discussion: This manuscript outlines the key features of the NOTACS statistical analysis plan and was submitted to the journal before the final analysis in order to preserve scientific integrity under an adaptive design framework. A previous version of this SAP was published prior to the interim analysis (Dawson, 2022). The NOTACS SAP closely follows published guidelines for the content of SAPs in clinical trials (Gamble, 2017).

Trial registration: ISRCTN14092678 . (13 May 2020).

Background: A cluster randomised trial is a randomised controlled trial in which groups of individuals (clusters) are randomised to treatment arms. Stepped wedge cluster randomised trials are a type of cluster randomised trial where clusters are randomised to sequences. These trial designs are important for impacting decision-making, and it is therefore important that they be well-conducted and reported.

Main body: In November 2018, we created a new website dedicated to cluster randomised trials, including stepped wedge designs: https://clusterrandomisedtrials.qmul.ac.uk/ . The idea for the website emerged from the conference on Current Developments in Cluster Randomised Trials and Stepped Wedge Designs held in November 2016 at Queen Mary University of London, with the aim to provide an online resource to facilitate quality trials and methodological research on these types of trial. The website is divided into sections covering Design, Analysis and Reporting for traditional (i.e. parallel two-arm) cluster randomised trials and stepped wedge designs and contains resources in the form of hyperlinks to relevant papers along with brief explanations. A noticeboard page provides details on announcements, events, and past events.

Conclusion: We aim to keep the site updated with the latest publications and events related to cluster randomised trials, and welcome suggestions from the research community on further resources or events to add. We hope that the site will facilitate high-quality traditional and stepped wedge cluster randomised trials.

Background: Scientific advancement, including the testing and licensing of new drugs, relies heavily on clinical trials with healthy individuals. The motivations of clinical trial participants have been discussed intensively, as some worry that financial compensation may distract from the intrinsic risk of clinical research. Herein, we investigated the motivations and decisional factors influencing SARS-CoV-2 clinical trial participants. Moreover, since most surveys are administered after clinical trial participation, we were interested in whether the results were tainted by recall bias.

Methods: This was a cross-sectional observational study. Participants were administered a survey on two occasions, once before and once after participation in a clinical trial. The primary outcomes were the motivations and decisional factors of SARS-CoV-2 vaccine trial participants and the difference between the surveys collected before and after clinical trial participation.

Results: The survey response rate was 149/200 (75%). SARS-CoV-2 vaccine trial participants were mostly motivated by the desire to contribute to science and help others. Answers collected before and after the trial were not statistically different, indicating the absence of recall bias.

Conclusion: The decision-making process of clinical trial participants is complex and multi-faceted. Previous studies have shown that clinical trial participants have mixed motivations but never to the extent reported in the current survey. Here, we present a theoretical framework that attempts to explain how different motivational factors may contribute to decision forming.

Background: Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties.

Methods: This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24-48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB).

Discussion: Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints.

Trial registration: Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021-002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277-8523.

Background: Globally, moderate wasting affects approximately 33 million children. Complex bidirectional interactions exist between wasting and infection in children. Children who experience both conditions have an increased risk of adverse outcomes including progression to severe wasting and mortality. Breaking the cycle between moderate wasting and infection could help improve growth and survival in these children. The NUTRIMAM trial will aim to investigate the efficacy of a 12-week regimen of three different nutritional interventions in at-risk young children (i.e., children who are moderately wasted and have one/more acute infections) on anthropometric recovery. Further, the study will explore whether recovery can be sustained with a post-intervention package that includes counseling and food vouchers. Sustaining anthropometric recovery beyond supplement administration will have important implications for programs.

Methods: NUTRIMAM is a multi-country, multi-center individually randomized, open-label, trial in five countries including Bangladesh, India, Mali, Pakistan, and Tanzania. A total of 6360 moderately wasted children aged 6 to 24 months with acute illness will be enrolled at health centers. Children will be randomly allocated to receive one of three dietary supplements (locally available foods, ready-to-use supplementary foods, or microbiota-directed supplementary foods) for 12 weeks. Anthropometric recovery will be assessed over this period. Participants who recover will then be re-randomized to a post-recovery support intervention comprising either counseling and food vouchers or routine standard of care for recovered children for an additional 12 weeks to determine if this intervention facilitates sustained recovery at 24 weeks.

Discussion: Children who are moderately wasted and have an infection are at higher risk of adverse outcomes. There are very few clinical trials that have been performed among children with moderate wasting with infectious illnesses to investigate if it is possible to break the undernutrition-infection cycle and thereby reduce the risk of nutritional deterioration to severe wasting or mortality and decrease the risk of acute infections. The results of the trial are anticipated to fill important evidence gaps in feeding recommendations for moderately wasted children with acute illness as well as interventions to sustain anthropometric recovery in children beyond the period of the nutritional intervention.

Trial registration: ISRCTN registry, ISRCTN53213318 . Registered on April 03, 2023.

Background: Coronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended.

Methods: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, randomised, Bayesian adaptive platform trial evaluating different booster vaccine interventions in immunocompetent children and adults, stratified by their primary vaccination schedule and age. Participants are randomised to receive one of three licensed COVID-19 booster vaccines available for use in Australia. PICOBOO aims to generate evidence about the immunogenicity, reactogenicity, and cross-protection of different booster vaccine strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants/subvariants. The protocol structure specifying PICOBOO is modular and hierarchical. We have previously published the PICOBOO core (master) protocol. Here, we detail the substudy protocol which outlines the study processes which are specific to PICOBOO participants enrolled in the booster vaccination substudy.

Discussion: PICOBOO is an adaptive platform trial evaluating different COVID-19 booster vaccination strategies to generate evidence to inform immunisation practice and policy. The modular and flexible protocol structure is intended to enable investigators to respond with agility to new research questions as they arise, such as immunogenicity targeting emergent virus variants, and the immunogenicity and reactogenicity of new vaccines as they become available for use.

Trial registration: Australian and New Zealand Clinical Trials Register ACTRN12622000238774; registered on 10/02/2022. Protocol V8.0_23112023.