Trials最新文献

Background: Traumatic brain injury (TBI) in the U.S. military can result in lasting health issues, with insomnia being a common symptom that worsens recovery, cognitive function, and performance, especially when combined with common co-occurring conditions like chronic pain, post-traumatic stress disorder (PTSD), and depression. Insomnia may be an important intervention target for managing post-concussive symptoms and overall functioning in service members who have sustained a TBI. However, the standard of care for the treatment of insomnia, Cognitive Behavioral Therapy for Insomnia (CBTI), is not widely available in military health care settings. The aim of this paper is to describe the design and analysis plan of the clinical trial to evaluate and compare two methods for delivering CBTI including in-person CBTI or CBTI delivered remotely via a clinician-supervised digital platform in a sample of active-duty service members presenting for care in a military TBI specialty clinic.

Methods: This is a phase II, randomized clinical trial designed to evaluate and compare the effects of CBTI (in-person or via a digital health platform) on sleep, behavioral health, and cognitive functions relative to treatment as usual among a sample of service members with a history of TBI. The effectiveness of in-person CBTI and CBTI delivered via a digital health platform, relative to treatment as usual, will be compared at baseline, after the six-week intervention, and again three months later on symptoms of insomnia, sleep quality, post-concussive symptoms, neurocognitive functioning, and psychological health.

Discussion: TBI is common in military personnel, often leading to insomnia that affects health and performance. While CBTI is the first-line recommended treatment for insomnia, CBTI is rarely implemented as the standard of care in military TBI specialty clinics, highlighting the need to assess its role in treating post-concussion symptoms and related issues. Clinical trials evaluating insomnia treatment in U.S. military service members with a history of TBI are essential to inform clinical practice for military TBI patients affected by insomnia and to potentially improve recovery, duty readiness, and cognitive function in this population.

Trial registration: ClinicalTrials.gov: NCT06867666. Registered on 2/26/2025.

Background: Pancreatic cancer surgery is challenging and associated with up to a 70% complication rate, which translates to poor postoperative recovery and patient health-related quality of life (HRQoL). Previous studies showed that preoperative low functional capacity and malnutrition have been associated with inferior postoperative outcomes. Considering the high frequency of older and frail patients, often deconditioned by long-course neoadjuvant chemotherapy, the preoperative period, including the time window after chemotherapy, is a unique opportunity to condition modifiable risk factors (e.g., functional capacity, nutritional status). This manuscript outlines the protocol for a randomized controlled trial investigating the impact of a multimodal prehabilitation program on postoperative complications and recovery following pancreatectomy.

Methods: This is a single-center, randomized controlled trial evaluating a 4-6-week multimodal prehabilitation program (physical, nutritional, and psychological interventions) compared with usual perioperative care in adults scheduled for pancreatic surgery, whether upfront or following chemotherapy for pancreatic or periampullary cancer. The primary outcome will be the severity of postoperative complications, measured using the Comprehensive Complication Index (CCI^®). Secondary outcomes include the level of functional capacity, time to functional recovery, length of stay, body composition parameters, and generic and disease-specific health-related quality of life (HRQoL). Follow-up assessment will be conducted at 30, 60, 90, 180, and 365 days post-surgery. A sample size of 238 patients is estimated to provide adequate power to detect a clinically meaningful difference in CCI^® between groups.

Discussion: A multimodal prehabilitation program may enhance functional capacity, improve nutritional status, and increase skeletal muscle mass, thereby promoting a shift from a catabolic to an anabolic state. By modulating systemic inflammation and supporting cardiovascular and immune function, this strategy could lead to fewer postoperative complications, a shorter length of stay, and a faster recovery of health-related quality of life. Positive findings from this trial would carry strong clinical significance and could be practice-changing, potentially informing future guidelines for the implementation of multimodal prehabilitation in patients undergoing pancreatic cancer surgery.

Trial registration: Trial Registry NCT06069297. Registered on August 25, 2023.

Background: Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg.

Methods: This multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring.

Discussion: This study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa.

Trial registration: ClinicalTrials.gov NCT05575518. Registered on 10th October 2022.

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.