Trials最新文献

Background: Progress towards elimination and eventual eradication of malaria is threatened by challenges such as the rise in insecticide resistance and low coverage of existing vector control tools. Spatial repellents offer personal and household protection against biting mosquitoes by disseminating repellents into a given area. The trial described here aims to evaluate the efficacy of an active transfluthrin-based spatial repellent device (Mossie-GO™) against malaria in Uganda, using a placebo-controlled, double-blinded cluster randomised control trial. The study's primary objective is to demonstrate and quantify the protective efficacy of Mossie-GO™ in reducing the prevalence of malaria infection in children ≤ 5 years of age. The study's secondary objectives are to measure the impact of the intervention on entomological correlates of transmission, to determine user acceptance of the device and to quantify transfluthrin concentration in the air.

Methods: The trial has fifty-six clusters randomly assigned in a 1:1 ratio to either the intervention or placebo-control arm. One hundred children at baseline and sixty children ≤ 5 years of age will be sampled in each cluster at 6 and 12 months to measure the primary endpoint. Each child will be sampled from a different household to avoid within-house replication. A subset of households from each cluster will be selected for secondary endpoint sampling. All households enrolled into the study will be encouraged to continue use of other malaria control tools.

Discussion: Trial results will contribute to the growing research on spatial repellent efficacy in sub-Saharan Africa and will inform recommendations for the use of spatial repellents in malaria control, specific to rural and peri-urban contexts in Uganda. Information on household characteristics, behaviour related to malaria exposure and user acceptability of the intervention will also be collected to improve understanding of the intervention usage and impact. Following the trial, results will be publicly disseminated.

Trial registration: The trial is registered with ClinicalTrials.gov 01/04/2024 unique identification (ID): NCT06232954.

Background: Knee osteoarthritis (OA) is the most common chronic arthritis and is a leading cause of pain and disability. Chronic care model (CCM) has been proved successful in Hong Kong primary care setting. This study aims to assess the clinical effectiveness of a CCM, named Assessment and Management Program on Knee Osteoarthritis (RAMP-Knee OA), compared to usual care in adults with knee OA.

Methods: The study is a 52-week, two-arm, parallel, open-label randomized clinical trial, evaluating the clinical efficacy of RAMP-Knee OA (N = 114) versus usual care (N = 114) on self-reported knee pain and other secondary outcomes. Measurement instruments will be tested at baseline, 16, 32, and 52 weeks. The primary outcome will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; 5-point Likert) pain at 52 weeks. Secondary outcomes include a set of biopsychosocial parameters: Physical function will be measured subjectively by WOMAC function subscale and objectively by the 30-second chair and stand performance test. Lower limb muscle mass will be measured by bioimpedance analysis. Physical activity level will be measured by the Chinese International Physical Activity Questionnaire (Short form). Self-management efficacy will be measured by Pain-Self Efficacy questionnaire. Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) will be used to measure anxiety and depression, respectively. Insomnia will be measured by the 7-item Insomnia Severity Index (ISI), and loneliness will be measured by the 6-item De Jong Gierveld Loneliness Scale. EuroQuol-5D questionnaire will be used to measure health-related quality of life. Both primary and secondary outcomes at different points will be conducted using analysis of covariance, adjusting for baseline values. Secondary analyses include adjustments for potential confounders and exploration of interaction effects of treatment and the potential moderators.

Discussion: The findings will address the evidence-to-practice gap for the implementation of a CCM that incorporates a comprehensive risk assessment, care protocol, self-management support, and scheduled health assessments in Hong Kong.

Trial registration: ClinicalTrials.gov, 1 NCT06283147. Registered on 22 February 2024.

Background: Advanced Trauma Life Support® (ATLS®) is the most widely adopted form of trauma life support training worldwide, but there is no high-quality evidence that it can improve patient outcomes. The aim of this trial is to compare the effects of ATLS® training with standard care on outcomes in adult trauma patients.

Methods: ADVANCE TRAUMA is a batched stepped-wedge cluster randomised controlled trial in India, where ATLS® is not routinely implemented. The trial will be conducted in 30 clusters (hospitals), organised into six batches of five clusters each. All clusters transition through three phases: first, a standard care phase; second, a 1-month transition phase, during which the training is delivered; and finally, an intervention phase, for a total of 13 months. Each cluster is randomised to an implementation sequence that defines the duration of the standard care and intervention phases. The trial will include at least 4320 adult trauma patients (≥ 15 years) who present to emergency departments and are subsequently admitted or transferred for admission. The primary outcome is in-hospital mortality within 30 days of arrival at the emergency department.

Discussion: This will be the first large-scale trial to provide robust evidence of the effectiveness of ATLS® since the programme was initiated in 1978. Regardless of the findings, this study will have important implications for trauma life support training globally. If ATLS® training improves patient outcomes, ways to promote its use and optimise its implementation, especially in low- and middle-income countries such as India, should be explored. If patient outcomes do not improve, trauma life support training must change.

Trial registration: Clinical Trials Registry-India (CTRI/2024/07/071336), ClinicalTrials.gov (NCT06321419, first registered 2024-03-20).

Background: Alcohol use disorder (AUD) represents a highly prevalent, costly, and often untreated condition in the United States. Post-traumatic stress disorder (PTSD) represents a common comorbidity with AUD which worsens outcomes and decreases functional outcomes. Suvorexant (SUV) shows clear promise as a novel therapeutic candidate to treat AUD and PTSD.

Methods: This study features a promising compound (i.e., suvorexant), the application of a well-established human laboratory paradigm (i.e., alcohol cue reactivity), and a novel early efficacy laboratory model (i.e., practice quit attempt) to provide a cost/time-efficient evaluation of safety and initial efficacy of suvorexant for AUD with comorbid PTSD. Additionally, by collecting both objective and subjective sleep measures, the study provides an assessment of a putative mechanism through which suvorexant jointly addresses an intervening variable common to both AUD and PTSD.

Discussion: The combination of human laboratory modeling and real-world clinical outcomes provides a unique and synergistic set of data that can advance the development of suvorexant and identify its behavioral mechanisms of action. The recruitment of individuals with AUD and PTSD with sleep disturbances and who are intrinsically motivated to quit is a novel approach to screening pharmacotherapies by bridging the gap between experimental studies with non-treatment seekers and clinical trials with treatment-seeking individuals.

Trial registration: ClinicalTrials.gov NCT06679062 "Suvorexant for Treatment of AUD and PTSD (SUV)." Registered on November 12, 2024.

Background: Despite the widespread adoption of uniportal video-assisted thoracoscopic surgery (VATS), postoperative pain associated with this procedure remains a significant concern. Effective postoperative analgesia is essential for facilitating the recovery of patients undergoing thoracic surgery. Thoracic paravertebral block (TPVB) is widely recognized as an extremely effective method of analgesia in such surgeries. Our previous study has demonstrated that the diffusion of local anesthetic during nerve blocks is related to body position. Therefore, this study aimed to evaluate the impact of thoracic paravertebral nerve block in various body positions on the analgesic outcomes for patients undergoing single-port thoracoscopic lung resection.

Methods: A randomized controlled trial was conducted to assess the impact of different body positions during thoracic paravertebral nerve blocks on the analgesic effect in patients undergoing single-port thoracoscopic partial lung resection. Patients scheduled for thoracoscopic lung resection will be included in this study. Participants (n = 200) will undergo thoracic paravertebral nerve block under ultrasound guidance. After the injection of the drug, they will be placed in either a supine position or a lateral position with the puncture side up. The NRS scores will be assessed at 1 h, 2 h, 8 h, 12 h, 24 h, and 48 h postoperatively. Postoperative opioid consumption, rescue analgesia time and frequency, patient satisfaction, incidence of adverse reactions, and length of hospital stay will also be recorded.

Discussion: This research project mainly aimed to investigate the impact of different perioperative positions for thoracic paravertebral nerve block on the analgesic effects in patients undergoing single-port thoracoscopic lung resection. The results may provide important implications for the development of effective analgesic strategies and robust clinical evidence to support the recovery of patients undergoing thoracic surgery.

Trial registration: ClinicalTrials.gov NCT06789276. Registered on 10 January 2025.

Background: There are few effective treatments for acute whiplash-associated disorder (WAD) following a road traffic crash. Early clinical features of central sensitisation, for example widespread hyperalgesia, predict poor recovery. Pregabalin's effects on central sensitisation suggest the potential to prevent or modulate these processes after whiplash injury and prevent later chronic pain. Preliminary evidence indicates that pregabalin provided in the Emergency Department and within 96 hours of injury shows promise to prevent chronic pain. This trial aims to definitively evaluate, in patients at risk for poor recovery following whiplash injury, the effectiveness of early (within 96 hours of injury) pregabalin, compared to placebo, to reduce pain severity.

Methods: The PReventing chronic pain after whiplash Road Traffic Injury (PRioRTI) study is a 12-month randomised, placebo-controlled, triple-blind trial. Individuals with acute WAD (aged 18-70 years) and at risk of poor recovery (pain ≥ 5/10) will be recruited from hospital Emergency Departments in Australia. Participants will be randomly assigned 1:1 to receive pregabalin or placebo. All participants will additionally receive an evidence-based advice booklet. Pregabalin will be commenced at 75 mg bd and titrated to 300 mg bd over 4 weeks, then weaned for 2 weeks. Participants will complete online questionnaires at 6 weeks and 3, 6 and 12 months post-randomisation. The primary outcome will be average pain intensity over 24 hours (0-10 numerical rating scale) at 3 months post-randomisation. Secondary outcomes include disability, patient global impression of recovery, psychological distress, quality of life and the number of adverse events. A cost-effectiveness analysis will be conducted. Potential mediators of treatment effects will be explored. A process evaluation will be conducted to explore barriers and facilitators for future implementation.

Discussion: There are few effective treatments for acute WAD. To address this gap, the PRioRTI trial aims to improve health outcomes by targeting central nociceptive processes very soon after whiplash injury using a readily available medication, pregabalin. If successful, the results of this trial will address an urgent unmet need to reduce pain severity after injury and will have clear implications for the early treatment of patients with whiplash injury. TRIAL REGISTRATION {2A AND 2B}: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12624001359527. Registered 13th November 2024.

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.