Trials最新文献

Background: Spinal pain is a highly prevalent condition affecting a large part of the population. Chiropractic maintenance care (MC) is a management strategy intended to prevent spinal pain recurrent episodes and deterioration by treating patients at pre-planned intervals. A previous study showed that patients identified as a dysfunctional subgroup by the West Haven-Yale Multidimensional Pain Inventory (MPI) and receiving MC had fewer days with bothersome LBP. This suggests MC may have superior effectiveness in this subgroup of patients. The MPI, however, is not practical for daily clinical practice, prompting the development of the MAINTAIN instrument. This study aims to (1) assess the effectiveness and cost-effectiveness of stratified MC using the MAINTAIN instrument, and (2) assess the fidelity and procedure compliance of implementing the MAINTAIN instrument.

Methods: This pragmatic randomized clinical trial will recruit 225 consecutive patients (18-65 years old) with significant (> 30 days in the past 12 months) recurrent spinal pain presenting to chiropractic clinics. After the initial 3 weeks (6 visits) of chiropractic care, patients will be randomized to receive either Stratified MC or Standard Chiropractic Care. Stratified MC: patients will complete the MAINTAIN instrument and be stratified to MC or symptom-guided care (clinicians' judgment). Patients in the Standard Chiropractic Care arm will receive standard treatment based on the chiropractor's judgment. The primary outcome is the total number of days with activity-limiting pain measured at 12 months. Secondary outcomes include the number of missed working days and loss of work productivity due to pain, pain intensity, disability, health-related quality of life, perceived improvement, and implementation of MAINTAIN instrument outcomes. An intention-to-treat protocol and generalized estimating equations (GEE) linear regression models will be used for analysis.

Discussion: This study investigates the impact of using a clinical instrument to identify patients with recurrent spinal pain to target those who benefit most from a chiropractic MC approach. Strict inclusion criteria should ensure a suitable target group, and frequently collected repeated measures should provide accurate outcome assessment. The study is pragmatic and includes standard clinical procedures facilitating the generalizability and transferability of the results into clinical practice.

Trial registration: ClinicalTrials.gov NCT05350254. Prospectively registered on April 22, 2022, last modified on December 08, 2023. The first patient was randomized into the study on December 21, 2023.

Background: Outpatient surgery means that the patient patient has surgery and often goes home on the same day. Safety and utilization outcomes were similar between outpatient and inpatient bariatric surgeries, and outpatients were associated with shorter hospital readmission lengths of stay. At the same time, it is necessary to evaluate how the possibility of accommodating an operated patient, for example, in an apartment integrated with the Ambulatory Surgical Center (ASC), will allow for discharge on the same day or one day after surgery. The researchers suggest that the differences in the "increased length of stay" criterion between the "same-day" (outpatients) and "one-day" (inpatients) groups after the procedure are minor. The safety and readmission rates of outpatients and inpatients who underwent laparoscopic gastric bypass using FundoRing were comparable. The objective of this study was to first aim to assess the cases of the extra length of stay of the pre-planned discharge date and the difference and reason between the "fit for discharge" and "actual discharge" dates. The second aim was to assess the safety and readmission of outpatient same-day and one-day laparoscopic one anastomosis gastric bypass by using the "FundoRing" method with an enhanced recovery protocol and remote monitoring in the ambulatory surgery center with integrated apartments.

Methods: The study design was a single-center prospective, interventional, open-label (no masking) RCT with 1-year follow-up. Adult obese patients (n = 200) were randomly allocated to one of two groups. Experimental surgical bariatric group: first (A) group: patients (n = 100) (Same-DayFundoRingOAGB group); active comparator surgical bariatric group; second (B) group: patients (n = 100) (One-DayFundoRingOAGB group). The Same-DayFundoRingOAGB group was assessed as outpatients and the One-DayFundoRingOAGB group as inpatients.

Discussion: The study participants were divided into two groups based on their discharge date. This study identified subjective and objective factors influencing discharge timing. It will answer the question: How can the difference between the "fit for discharge" and "actual discharge" dates be minimized? What interventions could have influenced this? An answer will also be given to the question: How can an apartment integrated with the ASC reduce the extra length of stay at the ASC?

Trial registration: ClinicalTrials.gov ID: NCT07189416. The Same-Day trial was retrospectively registered on 09.22.2025.

Background: Abdominal pain is a cardinal symptom of pancreatitis, present in up to 90% of patients with recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Increases in pain severity and constancy are associated with significant morbidity including depression and anxiety symptoms, low physical functioning, sleep disturbance, and low quality of life, as well as high economic and societal burden. Our pilot study of digital cognitive-behavioral therapy (CBT) demonstrated preliminary efficacy in improving pain and disability in adults with recurrent acute and chronic pancreatitis pain. Building on these promising findings, this hybrid effectiveness-implementation clinical trial seeks to test the effectiveness of digital CBT in a large sample and to gather data on future implementation of this scalable intervention.

Methods: This multisite, pragmatic clinical trial is recruiting 280 adults (ages 18 +) with recurrent acute or chronic pancreatitis who report chronic pain. Participants are randomized 1:1 respectively to one of two groups: (1) Digital CBT, providing access to the Pancreatitis Pain Course to learn pain self-management skills (e.g., relaxation, activity pacing, goal setting), or (2) Digital Pain Education (access to education website about pancreatitis pain). Evaluations are completed at baseline, 2 months, and 6 months follow up. This study leverages resources of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC), a NIH-sponsored U01 consortium, with recruitment from their nine clinical centers and from self-referral in the community through partnerships with community-based and clinical organizations. Relevant stakeholder groups (patients, providers, organizational managers) will participate in a process evaluation to inform future implementation in clinic and community settings. Primary effectiveness outcomes are pain interference and severity. Secondary outcomes include opioid use, depression, anxiety, quality of life, and sleep.

Discussion: Findings from the IMPACT-2 trial will significantly advance solutions for non-pharmacological pain management in RAP and CP. If successful, our project will address a critical need for low-cost, accessible pain self-management.

Trial registration: NCT06386224; first posted: 04-26-2024.

Background: Chronic stress is detrimental to the maintenance of the main response system - the hypothalamic-pituitary-adrenal (HPA) axis. The current study aimed to investigate the efficacy of two plant-based adaptogens, a formula containing Rhodiola, holy basil and Schisandra chinensis (VL-G-A57) and a full-spectrum ashwagandha (VL-G-E12), on stress and related symptoms in individuals with high stress.

Materials and methods: The 60-day randomized, double-blind, placebo-controlled clinical study included individuals aged between 18 to 65 years with a body mass index (BMI) of 18 to 29.9 kg/m². One hundred eighty-six participants were randomized to one of the adaptogens, VL-G-A57 or VL-G-E12, or to placebo. The primary outcome was a reduction in stress levels. Secondary outcomes were changes in sleep quality, fatigue, restorative sleep, mental alertness, mood dysregulation, and anxiety. A priori power analysis determined the required sample size. Efficacy was assessed by comparing mean changes in the primary endpoint at days 30 and 60 using ANCOVA, with baseline values as covariates. Dunnett's post hoc test identified significant differences versus placebo, and within-group changes were evaluated using paired t-tests. Normality was assessed visually and via Shapiro-Wilk/Kolmogorov-Smirnov tests as needed. Secondary outcomes were analyzed similarly. Analyses were conducted using R (v4.0.5) and XLSTAT (v2021.3.1).

Results: At day 60, both VL-G-A57 and VL-G-E12 significantly reduced Perceived Stress Scale (PSS) scores compared to placebo (p < 0.0001). Sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), improved significantly in both adaptogen groups (VL-G-A57: p = 0.0008, VL-G-E12: p < 0.0001). This corresponded well with the Restorative Sleep Questionnaire-Weekly (RSQ-W) results in the two IP arms when compared with placebo (p < 0.0001). Additionally, mood dysregulation (VL-G-A57: p = 0.0454), anxiety (VL-G-A57: p = 0.0004, VL-G-E12: p = 0.0015), and stress levels (VL-G-A57-VL-G-E12: p < 0.0001) showed significant improvements compared to placebo. No differences in mental alertness were observed.

Conclusion: The study concluded that both VL-G-A57 and VL-G-E12 were associated with reductions in stress, fatigue, and anxiety while improving mood and sleep quality.

Trial registration: ClinicalTrials.gov NCT05602389 and the Clinical Trials Registry - India CTRI/2022/11/047635. Registered on 1 November 2022 and 24 November 2022.

Background: Discomfort while using soft contact lenses is a major concern in eyecare, and it is strongly linked to dry eye. Many new dry eye therapies have not yet been studied on contact lens users. Cyclosporine is a pharmaceutical agent that has recently been re-engineered in a nanomicellar drop. Intense pulsed light is a potent treatment for meibomian gland dysfunction. Very little data exists on the effects of these treatments, and they have never been tested in combination. The aim of this study was to test the effects of the combination of nanomicellar cyclosporine and intense pulsed light on the symptoms and signs of soft contact lens users.

Methods: Forty-four symptomatic soft contact lens users will be recruited from a primary care optometry practice. They will receive cyclosporine 0.09% to use twice daily, and, after 8 weeks, they will be randomized to receive three sessions of intense pulsed light or a sham. Primary outcome will be the symptom score using a questionnaire, and secondary outcomes will include tear film stability measurements (both on the tear film and over contact lenses), tear meniscus height, osmolarity, meibomian gland atrophy, and ocular surface staining. Safety will be assessed by measuring visual acuity, intra-ocular pressure, and an adverse effects questionnaire. Questionnaire scores will be compared using a t-test, while other measurements will be analyzed using mixed-model effects.

Discussion: This study aims to test whether a combination of novel dry eye treatments that target the whole tear film improves comfort while wearing contact lenses. Discomfort is a major issue that leads to drop out. The results of this study could provide eyecare professionals with additional tools to help their patients and could open the discussion on future solutions to improve contact lens users' experience.

Trial registration: ClinicalTrials.gov NCT06392438, registered on April 23rd, 2024.

Background: Hip fractures are most commonly suffered by elderly patients, but 2-11% of hip fractures affect younger patients. In young adults with femoral neck fractures, internal fixation is the recommended treatment for both displaced and non-displaced fractures. However, treatment with internal fixation carries a high complication rate. A known complication of internal fixation after gold standard cannulated cancellous screws is fracture compression resulting in shortening of the femoral neck, which is associated with clinically important decreases in functional outcome. New osteosynthesis implants have been developed to prevent fracture compression and improve the outcomes of internal fixation of femoral neck fractures. Recent preliminary clinical and biomechanical studies show that implants with interlocking screws and/or angle stability have promising results compared to standard internal fixation with cannulated cancellous screws. Measurement and comparison of three-dimensional fracture displacement requires precise method, which may be accommodated with CT bone models and weight-bearing radiostereometric imaging in the months after surgery.

Methods: A total of 54 young adults under 65 years of age with femoral neck fractures will be electronically randomised to treatment with either internal fixation with cannulated cancellous screws (gold standard) or an angle stable implant (Dynaloc, Swemac). Patients will be excluded if they are unable to understand the study information, have a transcervical, basicervical or pathological fracture, or present clinically as frail. Primary outcome measure is fracture migration at 12 weeks measured in radiostereometric imaging using CT bone models and AutoRSA software. Secondary outcomes will be fracture migration in terms of femoral neck shortening at 6 weeks, function scores and pain Verbal Rating Scale at 6 and 12 weeks, surgical complications, reoperation and mortality at event.

Discussion: This clinical trial will examine fracture migration and the functional outcomes of internally fixated femoral neck fractures in young adults by comparing the results of an angle stable implant (Dynaloc, Swemac) compared with cannulated cancellous screws. The study has perspective to provide scientific evidence for empirical decision-making when choosing implants for femoral neck fractures in young adults.

Trial registration: ClinicalTrials.gov NCT06521671. Registered on July 22^nd, 2024.

A wide range of factors has detrimental impacts upon equity, diversity, and inclusion in clinical trials, amongst which participant burden can be significant. In addition to the potential physical burdens associated with investigational interventions, participants may face onerous demands related to factors like travel, time commitments, psychological, or logistical challenges. Many of these factors have been shown to create barriers that disproportionately affect certain groups like minoritised ethnic groups, people with caring responsibilities, and older adults. One increasingly problematic aspect of participant burden is associated with an excessive volume of data collection, much of which may lack direct relevance to the study's primary objectives and may never be analysed. Although pragmatic and participant-centred trial methodologies have risen in prominence over the past decade, quantitative evidence demonstrates that trial complexity and data volumes are continuing to rise. The widening gap between the notion of participant-centricity and the realities of current trial practice underscores the need for a shift in approach. Reducing unnecessary burden should be regarded as a moral obligation across all clinical trial designs to avoid the systematic exclusion of certain groups. With a focus on data-related aspects, this paper examines the ethical implications of undue burdens upon participants and proposes measures to help minimise and mitigate these burdens. In addressing this issue, researchers contribute to broader efforts to enhance inclusivity and representation in clinical studies.

Background: Exploring barriers and enablers to participant recruitment into trials is a common discussion point in trial methodology. Participant information leaflets (PIL) can be long, have complexity above the average UK reading age, and may discourage engagement with research. This Study Within a Trial (SWAT) explored whether changing the design of a PIL influences recruitment rate and its value in patient decision-making. It was conducted within a host trial taking place in an emergency setting, where time is at a premium, and decisions on trial participation are needed more quickly than in most non-emergency settings.

Methods: We have conducted a randomised SWAT, comparing the standard format PIL with one that has been adapted to be visually appealing, with improved readability and reduced word count. Patients considered eligible for the host trial were provided with a randomly allocated PIL type; consent rates were compared. Those consenting to take part in the host trial were asked to complete a questionnaire to explore the value of the PIL in their decision-making to take part in the trial; responses were compared across the two information sheets. The sample size was dictated by host trial recruitment.

Results: Between September 2019 and September 2022, with a brief pause during the COVID19 pandemic, 271 participants were randomised to receive either the optimised PIL (n = 138) or the conventional PIL (n = 133). The recruitment rates were 47.1% (65/138) in the optimised PIL group and 48.9% (65/133) in the conventional PIL group; this difference was not statistically significant (p = 0.771). There were no significant differences in responses from participants recruited to the host trial who completed the Decision-Making Questionnaire.

Conclusion: Improving the readability and visual presentation of the participant information sheet provided to participants had no effect on recruitment rate, and did not appear to impact decision-making of recruited participants.

Background: Medical cannabis is now commonly prescribed for a range of chronic health conditions. Many medical cannabis products contain delta-9-tetrahydrocannabinol (THC), the intoxicating component in cannabis, though it is unclear whether these products produce impairment when used as prescribed and at therapeutic doses. With current Australian laws prohibiting driving with any amount of THC in one's system, this trial aims to generate novel data on the impact of prescribed medical cannabis on real-world driving performance to inform road safety policy.

Methods: This is a two-phase trial, with the first phase being a semi-naturalistic cohort study involving 72 patients with physician-diagnosed chronic pain, anxiety, or insomnia (n = 24 per group) who will complete repeated on-track driving assessments before and after consuming a standard dose of their medical cannabis prescription. The second phase is a randomised, placebo-controlled, double-blind, and crossover study involving 24 healthy participants who will complete the same repeated on-track driving assessments before and after consuming either alcohol (0.05% blood alcohol concentration) or placebo. Participants in both phases will also complete repeated cognitive assessments and assessments of subjective state and provide biological samples for analysis of cannabinoid (phase 1) and alcohol (phase 2) concentrations. The primary outcome measure is lateral vehicular control. Data will be analysed using a series of mixed-effect and generalised linear mixed models to assess changes in outcome measures over time.

Trial registration numbers: ACTRN 17/09/2024 for 12624001118594 and 24/09/2024 for 12624001163594.

Background: Randomised controlled trials (RCTs) are the gold standard for evaluating treatment effects, with the results informing policy and clinical practice. To ensure appropriate methods are utilised and to avoid misinterpretation of the results of a clinical trial, it is vital that we understand the research question a trial aims to answer. However, there is often ambiguity in how trialists define their research questions. In 2019, an addendum to the international trial regulatory guidelines (ICH E9 (R1)) introduced the estimand framework to combat this. A review of protocols published in 2020 investigated the early adoption of the estimand framework and found no uptake as well as a lack of clarity on key items such as the handling of intercurrent events. The aim of this review was to identify the current application of the estimand framework specifically to trials with an adaptive design.

Methods: The search strategy aimed to identify trial protocols and statistical analysis plans that described RCTs published in two journals (BMJ Open and Trials) in 2023. Articles were eligible if they related to phase 2-4 trials with an adaptive design. A pre-piloted data extract form was used to extract data relating to study details, intercurrent events and estimands.

Results: One thousand five hundred and forty-one articles were identified by the initial search. Following screening, 146 articles were identified as meeting the eligibility criteria. Of the eligible articles, five (3%) stated their primary estimand, and of these, three (2%) stated all five estimand attributes. Ninety-four (64%) articles described one or more intercurrent events; these included a total of two hundred and thirty-two intercurrent events described. Fifty-two (36%) articles did not describe any intercurrent events. No articles specified the estimand for any planned interim analyses or considered the implications of adaptations on the primary estimand.

Conclusions: This review provides evidence that there is still a lack of uptake of the estimand framework in RCTs. Wider application of the estimand framework would ensure clarity in the reporting and interpretation of clinical trial results. In addition, clear guidance on how to implement the estimand framework to trials with an adaptive design is needed.