Trials最新文献

Background: Recurrent implantation failure (RIF) remains clinically unresolved at this stage. Hydroxychloroquine, as an immunomodulator, is still lacking clinical evidence, but it is being used by increasing numbers of reproductive centers and physicians worldwide, so a well-designed randomized controlled trial (RCT) is urgently needed to elucidate whether hydroxychloroquine can improve pregnancy outcomes in patients with RIF.

Methods and analysis: In this study, we plan to recruit 686 volunteers who will undergo IVF/ICSI at 5 reproductive centers from 6 December 2022. Participants will be randomized to two parallel groups and treated with hydroxychloroquine sulfate tablets or placebo from the start of endometrial preparation to 14 days after frozen embryo transfer (if not pregnant) or to 12 weeks of pregnancy (if pregnant). The primary outcome is live birth rate, and the secondary outcomes include biochemical pregnancy rate, clinical pregnancy rate, embryo attachment rate, first trimester abortion rate and ongoing pregnancy rate, birth weight, pregnancy and perinatal complications, congenital anomaly, and other adverse events.

Discussion: This study aims to evaluate whether hydroxychloroquine (HCQ) improves pregnancy outcomes in patients with recurrent implantation failure (RIF). Secondary objectives include comparative analysis of gestational complications between the intervention and control groups.

Trial registration: ChiCTR2100047584 [Chinese Clinical Trial Registry (ChiCTR): registered on 20 June 2021]. LM2021267 [Ethics Committee of Peking University Third Hospital].

Background: Inguinal hernia is a common disease, and laparoscopic tension-free inguinal hernia repair has become the standard procedure for treating inguinal hernia. During surgery, carbon dioxide gas is injected into the patient's abdominal cavity to maintain a specific pneumoperitoneum pressure. Under standard pneumoperitoneum pressure (SPP), we occasionally observe that some patients are prone to subcutaneous emphysema and hypercarbia, especially elderly patients with inguinal hernias, where the occurrence is relatively high. The aim of this study was to analyse whether using lower pneumoperitoneum pressure (LPP) in laparoscopic hernia repair is safer while maintaining surgical success.

Methods: This was a prospective, double-blind, randomized controlled study in which patients were randomly assigned to either the LPP group or the SPP group. The primary outcome measures were the results of patients' arterial blood gas analysis, including partial pressure of carbon dioxide (PaCO2), arterial oxygen partial pressure (PaO2), pH value, arterial oxygen saturation (SaO2), whole blood base excess (ABE), and standard base excess (SBE). The secondary outcome measures included heart rate, blood pressure, cardiac output (CO), stroke volume (SV), end-tidal carbon dioxide pressure (PetCO2), airway pressure (Paw), intraoperative complications, surgical duration, anesthesia recovery time, Length of hospital stay, postoperative pain, and quality of life. The aim of this study was to analyse the differences in these indicators between the two groups of patients.

Discussion: Compared with laparoscopic inguinal hernia repair performed under SPP, the use of LPP in laparoscopic inguinal hernia repair is advantageous for improving patients' blood gas analysis and systemic circulatory indicators. This study demonstrated that LPP for inguinal hernia repair is safe and effective, providing evidence-based support for the selection of pneumoperitoneum pressure values.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2400091218, Registered on October 23, 2024.

Background: The forefoot and rearfoot can individually contribute to the development of chronic ankle instability (CAI) after an ankle injury. The aim of this study is to evaluate the effects of targeted forefoot and rearfoot stability training on dynamic balance, postural stability, gait biomechanics, and self-reported joint function in individuals with CAI.

Methods: This study is a prospective, single-center, interventional, randomized controlled trial with two comparison groups, either a usual balance training group or a control group. Individuals (18-44 years) with a self-reported ankle instability, a history of at least one ankle injury at least 12 months ago with typical signs of inflammation, two or more episodes of "giving way" within the previous 6 months, and a Cumberland Ankle Instability Tool score ≤ 24 are included. Exclusion criteria include acute injury, lower extremity surgery or fracture, neurological disease, chronic overuse injuries such as Achilles or patellar tendinopathy, and current participation in a targeted ankle rehabilitation program. The primary outcome measures are dynamic balance as measured by the Y-Balance Test and postural stability as assessed by the Modified Balance Error Scoring System. Secondary outcome measures include gait biomechanics measured by 3D gait analysis and self-reported ankle function assessed by the Foot and Ankle Ability Measure.

Discussion: Since there is a lack of information regarding the effects of targeted forefoot and rearfoot exercises on ankle stability, this study has the potential to improve future treatment plans and provide healthcare practitioners with an alternative treatment for CAI.

Trial registration: DRKS (German Clinical Trials Register)-DRKS00034295, retrospectively registered on May 22, 2024 (Reason: The study was originally designed as a randomized controlled pilot study; therefore, the first participants were enrolled without registering the study, which was then caught up as soon as possible); URL: https://drks.de/register/de/trial/DRKS00034295/preview.

Background: Patients with self-harm and suicidal ideation are increasingly presenting in emergency departments (ED) in the UK. Self-harm is the strongest risk factor for suicide. Currently, there are no evidence-based interventions for self-harm offered in the context of general hospitals in the UK. This trial, funded by the National Institute for Health and Care Excellence (NIHR), aims to assess the clinical and cost-effectiveness of the ASSURED intervention. The ASSURED intervention includes up to five rapid follow-up contacts, comprising a narrative interview and enhanced safety planning session and three solution-focused sessions. The trial is sponsored by Devon Partnership NHS Trust and City St George's, University of London.

Methods: ASSURED is a multicentre, two-arm, parallel-group, individually randomised, controlled trial comparing the ASSURED intervention with usual care. The primary outcome is whether study participants re-attend ED and are referred to liaison psychiatry within 18 months from the date of randomisation. Secondary outcomes include suicidality, self-reported self-harm, psychological wellbeing, social outcomes, experiences of attending the ED, and suicide. The study will also evaluate the cost-effectiveness of the intervention. The aim of this study was to recruit and randomise 620 patients across 14 acute hospital sites in London, Devon, Somerset, and the Midlands. Participants are invited to complete research assessments at baseline and 3, 9, and 18 months. The first participant was enrolled in the study in August 2022, and the recruitment target was met in December 2024.

Discussion: This will be the first UK trial to test the effectiveness and cost-effectiveness of a rapid intervention for patients presenting to EDs with self-harm and suicidal ideation and has the potential to improve outcomes for these patients.

Trial registration: ISRCTN 13472559. Registered on 18 of November 2021.

Background: Dynamic treatment regimens (DTRs) guide personalised sequential treatment decisions for patients with a range of clinical or behavioural diseases. Sequential multiple assignment randomised trials (SMARTs) are designed to evaluate and optimise DTRs by randomising participants at multiple stages based on intermediate outcomes. To identify optimal DTRs in SMARTs, the mean outcome of each DTR is often estimated via inverse probability weighting (IPW), a statistical method that uses the inverse probability of treatment to address potential bias in the design. Like other randomised controlled trials, SMARTs are subject to missing data. Handling missing data in SMARTs is complicated by the sequential randomisation and dependence on intermediate outcomes. We evaluated the performance of complete case analysis (CCA) and multiple imputation (MI) for handling missing data when estimating the DTR mean outcomes using IPW in a two-stage SMART.

Methods: We simulated 1000 datasets of 400 participants, based on a prototypical SMART design with two stages where only non-responders are re-randomised at stage 2. The estimands of interest were the four DTR means of a continuous outcome and were estimated using IPW. We defined four plausible missing data scenarios using missing data directed acyclic graphs (m-DAGs) and then assessed how each missing data method (CCA and MI) performed under different proportions of missingness (20%, 40%) and strengths of associations with missingness in stage 1 intermediate outcome, stage 2 treatment, and the final outcome.

Results: Minimal bias was observed with MI when estimating the mean outcomes of the DTRs in most scenarios, except for when stage 1 intermediate outcome was missing dependent on baseline variables and stage 1 treatment. When data were missing dependent on other variables (for example, stage 2 treatment missing dependent on stage 1 intermediate outcome), CCA generally showed greater bias than MI when estimating the mean outcomes of the DTRs. Empirical standard errors were comparable across both missing data methods, with MI generally producing slightly lower values.

Conclusion: We found that for a prototypical SMART design, MI generally showed close to zero bias and slightly lower standard errors compared to CCA when IPW was used to estimate the mean outcomes of DTRs in the settings explored.

Background: The OMED2 (Optimization of Medication in Elderly with Diabetes) study addresses the effect and implementation of integrating a deprescribing programme (DPP) in general practice. The aim of the DPP is to reduce glucose-lowering medication (SU/insulin) in overtreated older patients. The protocol for this study has been published previously. This statistical analysis plan (SAP) contains a more elaborate outline of the (statistical) methods we plan to use for data analysis.

Methods: The OMED2 study is a randomized mixed-methods study with a 2-year follow-up period that compares the effect of the implementation of a DPP in general practice to regular care (control). In this SAP, we report on the (statistical) approaches that we plan to use to address the study objectives. The main objective of the OMED2 study is to examine the effect of the implementation of the DPP on diabetes complications, whereby the total number of diabetes complications related to undertreatment and overtreatment will be summed. Generalized linear mixed models with a Poisson distribution and the DPP as the main determinant will be used to test whether the total number of diabetes complications occurring from the start of the 2-year follow-up until the end of follow-up differs between intervention and control. The incident rate of the number of diabetes complications will be calculated to correct for possible differences in follow-up duration. The model will also include a random effect variable to allow for possible clustering effects by general practice. We will perform intention-to-treat analyses, which include all patients eligible for deprescribing, as well as per protocol analyses, which omit patients who were not deprescribed in the intervention arm. Additionally, approaches to study the implementation of the DPP and the cost-effectiveness of the implementation are outlined in the SAP.

Trial registration: ISRCTN Registry ISRCTN50008265. Registered on 1 November 2024.

Background: Gastroesophageal reflux disease (GERD) is a common condition in infants below 1 year of age. Symptoms include frequent regurgitation, failure to thrive, food refusal, irritability, and back arching. While many infants experience some degree of physiological reflux, persistent or severe symptoms may indicate GERD. One important underlying cause of GERD in infants is allergy to cow's milk protein. Current international guidelines recommend a trial of a cow's milk protein-free diet prior to initiating medical therapy with a proton-pump inhibitor. However, the efficacy of both the diet and the medication remains insufficiently studied. With only a few randomized trials available, further evidence is needed to ensure infants receive the most appropriate treatment.

Methods: This protocol describes a multicentre, randomized placebo-controlled trial, enrolling 96 infants with a clinical diagnosis of GERD at 3 paediatric centres in Southern Denmark. Eligible participants will be randomly assigned to one of three parallel groups: (1) A diet group receiving a cow's milk protein-free diet, (2) a medicine group treated with a proton-pump inhibitor, and (3) a control group receiving a placebo medicine. Both the PPI group and the control group will be blinded to the allocation and will continue a diet containing cow's milk protein. The intervention period is 4 weeks. The primary outcome is the reduction in the number of regurgitation episodes. Secondary outcomes include weight gain and reduction in GERD-related symptoms. Symptom data will be reported by parents using a digital application, and specific IgE to cow's milk protein will be quantified in all participants. Infants in the diet group who respond positively will undergo an oral milk challenge to confirm allergy to cow's milk protein.

Discussion: This trial is designed to provide evidence on the efficacy of a cow's milk protein-free diet and proton-pump inhibitor therapy for infant GERD. Both interventions are evaluated against a control group, ensuring that any improvement exceeds the natural course of symptom resolution over time. The findings will provide valuable insights to guide clinical practice and enhance treatment strategies for infant GERD, a condition with a substantial impact on infant health and family well-being.

Prospective trial registration: ClinicalTrials.gov NCT06255886. Registered on February 13, 2024.

Clinicaltrials: eu EU-CT: 2022-502770-16-00. Registered on November 4, 2024.

Background: Breast cancer is the most diagnosed cancer among women in the United States. While rates of advanced-stage breast cancer have declined overall, incidence is rising among Korean American women. Advanced-stage breast cancer is more frequent among Korean women compared to other Asian ethnic groups, largely attributed to low adherence to breast cancer screening. Church settings offer important opportunities for education as most Korean American women over age 50 regularly attend church services. The objective of this trial is to evaluate the efficacy of a culturally tailored intervention Faith in Action! on breast cancer screening adherence rates among Korean American women.

Methods: A parallel cluster randomized trial with staggered roll-out was designed to evaluate the efficacy of the Faith in Action! intervention, a church-based small group education and lay health navigator program, delivered by trained church members, on breast cancer screening among Korean American women (NCT05298605). The study was designed and will be conducted in partnership with our center's Community Outreach and Engagement (COE), which formed a Community Advisory Board. Twenty-four total Korean churches in Los Angeles will be randomized within blocks of 8 churches to either intervention or waitlist control conditions in a 1:1 ratio. Using a train-the-trainer approach, lay navigators from the Korean Church community nominated by church leadership will be trained by COE and certified to deliver the Faith in Action! intervention to study participants over a 6-month program period. Participants at churches randomized to the waitlist control group receive an educational presentation on physical activity and nutrition and, after 6-month follow-up, are invited to receive the Faith in Action!

Intervention: Eligible participants include women, ages 45-75 years, who attend a participating church in Los Angeles County, do not have a breast cancer diagnosis, and did not receive a mammogram in the last 2 years. The primary outcome is adherence to breast cancer screening guidelines within 6 months from the end of the intervention. Secondary outcomes include adherence to breast cancer screening within 1 year and knowledge on breast cancer screening.

Discussion: This study addresses a current need for developing and testing culturally tailored interventions to increase breast cancer screening adherence among Korean American women. Leveraging faith-based organizations and delivering the intervention through trained lay health navigators, if found to be effective, has the potential to provide a scalable and sustainable strategy for increasing screening rates and ultimately improve health and well-being as well as reduce cancer-related disparities in this population.

Trial registration: ClinicalTrials.gov NCT05298605. Registered on March 17, 2022.

Background: Post-traumatic stress disorder (PTSD) presents significant mental health challenges for veterans, leading to substantial physical, cognitive, and psychological difficulties, including heightened risks of social issues and suicidal ideation. Adaptive Disclosure (AD) is a novel, emotion-focused Cognitive Behavioral Therapy (CBT) approach developed by the military for combat-related PTSD. This technique involves exposure therapy and an empty-chair technique, allowing patients to verbalize unresolved issues. Despite its short, six-session duration, AD appears well-tolerated and effective in reducing PTSD symptoms. Given the limited global studies and their absence in Iran, this study will be conducted to investigate AD's impact on reducing PTSD symptom severity in veterans.

Methods: This randomized clinical trial will explore AD's effect on PTSD symptom severity. A total of 58 participants (29 per group) will be recruited via available sampling from Shahid Rajaee and Salman Hospitals in Yasuj. Participants must be veterans aged 18 or older, with diagnosed PTSD, sufficient insight for AD (assessed via Mental Status Exam), and informed consent. Exclusions include severe mental disorders (e.g., psychotic or bipolar type I), recent suicidal/homicidal ideation (within 3 months), or concurrent systematic trauma-focused therapies. The intervention group will receive six weekly 90-min AD sessions. The control group will receive no intervention during this period. Immediately after the intervention, both groups will complete the research questionnaire. Following the study, the control group will also be offered education on the Adaptive Disclosure technique. The primary outcome, severity of post-traumatic stress disorder symptoms, will be measured using the Post-Traumatic Stress Disorder Checklist- Civilian Version (PCL-C), a 17-item self-report scale. Data will be analyzed with SPSS version 27. Ethical approval has been secured from Yasuj University of Medical Sciences (Supplementary File 2).

Discussion: The results are expected to offer vital insights into AD's effectiveness for veterans with PTSD. If successful, this approach could inform policymakers for healthcare guidelines and aid psychiatric nurses in symptom alleviation. This research will significantly contribute to the scientific community by providing the first empirical evidence of AD's efficacy in an Iranian veteran population, expanding knowledge on culturally relevant treatments for combat-related PTSD, and potentially informing clinical practices nationally and internationally.

Trial registration: IRCT number IRCT20160815029377N4. Registered on 03/05/2025.

Background: In Malaysia, adolescent anxiety and depression are increasing faster than ever, and rates of suicidal behaviour are rising especially among those living in deprived communities. However, Malaysia's mental health system is currently constrained by limited workforce capacity, affecting the delivery of effective interventions. The overall aim of this trial is to use a school-based intervention to promote mental health among at-risk adolescents from low-income communities in Malaysia. Our primary aim is to evaluate the effectiveness and cost-effectiveness of a school-based intervention ("Super Skills for Life"; SSL) in reducing anxiety and depression, and in improving mental wellbeing in adolescents aged 12-14 years. We also aim to determine the characteristics of adolescents who benefit from SSL, compared to those who do not, as well as to identify contextual factors related to the successful implementation of SSL in Malaysian schools.

Methods: The design will be a two-arm, cluster randomised controlled trial comparing school-based intervention (Super Skills for Life; SSL) to study skills control condition (Study Skills Programme; SSP) using a 1:1 allocation ratio. Classrooms will be the cluster unit for randomisation. Three stratification factors will be used for randomisation: school size, classes/forms and school location (urban vs rural). The study will recruit adolescents in at least 20 secondary schools in economically deprived, rural and urban regions in Malaysia. These adolescents will be invited to complete a screening questionnaire (i.e. Depression Anxiety and Stress Scale-21; DASS-21). Based on power calculation, 428 adolescents (214 per arm) who experience moderate to severe levels of anxiety and depression on the DASS-21 will be invited to participate in the trial. Classes will be randomly allocated to SSL or SSP, with eligible adolescents from each class receiving the allocated intervention. Assessment will be conducted at screening, at pre- (i.e. baseline) and post-intervention (i.e. 2 months), and at two follow-ups (i.e. 6 and 12 months post-intervention). The primary outcomes will be a reduction in anxiety and depressive symptoms, and an improvement in mental wellbeing at 12 months post-intervention.

Discussion: Findings of this trial will determine if delivering a group school-based intervention by school staff for adolescents at risk of anxiety and depression is effective and cost-effective. The findings will advance understanding of the role of school staff in the delivery of a school-based intervention and will generate new knowledge on the role of socio-cultural and other contextual factors in predicting intervention uptake and treatment outcome.

Trial registration: ClinicalTrials.gov NCT07138664. Registered on August 16, 2025.