Trials最新文献

Background: High-frequency ventilation (HFV) is commonly used in neonatal intensive care units to provide respiratory support for critically ill neonates. Currently, there is no standardized procedure for weaning from HFV. Two commonly used strategies are transitioning from HFV to conventional mechanical ventilation (CMV) before extubation (HFV-CMV) and extubation after decreasing mean airway pressure during HFV (HFV-HFV). The impact of these strategies on neonatal cerebral oxygenation and hemodynamics remains incompletely understood.

Methods: We will conduct a prospective, single-center, randomized controlled trial to investigate the effects of two different HFV weaning strategies (HFV-CMV, HFV-HFV) on neonatal cerebral oxygenation and hemodynamics. The patients enrolled in the trial will be randomly allocated to either the HFV-CMV group or the HFV-HFV group in a 1:1 ratio. The primary outcome will be cerebral oxygen saturation (S_cO₂) before and after the intervention. Second outcomes are cerebral fractional tissue oxygen extraction, heart rate, blood pressure, and the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia. We hypothesize that HFV-CMV results in positive impact on neonatal cerebral oxygenation compared to HFV-HFV. This study aims to identify a better weaning strategy for HFV and contribute evidence-based data to enhance its clinical application in newborns, potentially improving the care and outcomes for neonates receiving HFV.

Discussion: This study aims to assessing the impact of different HFV weaning strategies on neonatal cerebral oxygenation and hemodynamics, as well as the relationship between the duration of HFV under different strategies and neurological complications, to identify better weaning methods for HFV. We hope to contribute evidence-based data to enhance clinical application of HFV in newborns, potentially improving the care and outcomes for neonates receiving HFV.

Trial registration: Chinese Clinical Trial Registry: ChiCTR2400088628. Registered on August 22, 2024, https://www.chictr.org.cn/bin/project/edit?pid=235926 .

Background: Perinatal depression affects 10-15% of mothers and approximately 5% of fathers. However, only a small number of affected individuals seek treatment. If left unrecognized and untreated, it can have negative long-term consequences for the family's health, leading to subsequent high costs. Early treatment is crucial, yet there is a notable underdiagnosis and undertreatment. Affected individuals are often seen during this time, e.g. in paediatric practices, but not by specialists in mental health. Consequently, this study aims to increase detection and treatment rates of affected individuals by implementing a screening for depression and psychosocial stress in perinatal and postpartum parents within routine obstetric and paediatric care with subsequent advice and-if necessary-further referral to a mental health specialist.

Methods: UPlusE is a prospective, cluster-randomized controlled trial conducted in an outpatient setting. Obstetric and paediatric practices will be randomized into an intervention and control group (1:1 ratio). Practices and enrolling patients will be required to use specific smartphone apps (practice apps) for interaction. The screening will occur with the apps at each paediatric checkup up to the child's age of 12 months, using the Edinburgh Postnatal Depression Scale (EPDS), KID-PROTEKT questionnaire, and the scale 1 (impaired bonding) of the Postpartum Bonding Questionnaire (PBQ-1). The goal is to screen 10,000 patients across Germany. Gynaecologists and paediatricians will receive certified training on peripartum depression. Participants in the intervention group with scores above cut-offs (EPDS ≥ 10, KID-PROTEKT ≥ 1, PBQ-1 ≥ 12) will receive counselling through their treating gynaecologists/paediatricians and will be provided with regional addresses for psychiatrists, psychotherapists, and "Frühe Hilfen" (early prevention) as well as family counselling centres, depending on symptom severity. At each screening, participants will be asked whether they sought support, where, and with whom (utilization). Utilization is the primary outcome.

Discussion: The screening is designed to reduce underdiagnosis to enable suitable support at an early stage (especially for those often overlooked, such as individuals with "high-functioning depression") and hence to avoid manifestation of mental health problems in the whole family, especially infants who are exceptionally dependent on their parents and their well-being will benefit from this program.

Trial registration: German Clinical Trials Register, DRKS00033385. Registered on 15 January 2024.

Background: Among the most powerful barriers to broader inclusion of diverse participants in clinical trials are social determinants of health, trustworthiness of health care providers and research institutions, and competing pressures on potential participants. Nevertheless, current tools to assess organizational capabilities for clinical trial diversity focus primarily on trial infrastructure, rely solely on quantitative self-reported data, and lack meaningful assessment of capabilities related to community engagement.

Methods: The Equitable Breakthroughs in Medicine (EQBMED) initiative developed a holistic, collaborative, site-driven formative model and accompanying assessment to catalog sites' current capabilities and identify opportunities for growth in both conducting industry-sponsored clinical trials and enriching diversity of those trials. The model builds upon prior work and reflects unification of two historically distinct components-research operations and community engagement-since sustainable clinical trial diversity efforts must overcome these silos. Here we present the methodology we used to develop the model and accompanying assessment, describe how findings can support clinical trial diversity efforts, and report findings from early field testing at three U.S. sites.

Results: The first three sites were diverse in size (e.g., < 250-1 K beds), with varying levels of clinical trial capabilities and community engagement. The maturity assessment laid the foundation for sites to identify and prioritize key areas to advance clinical trial diversity capabilities, and each has made tangible progress. In parallel to completing the assessment with these early sites to understand their maturity and set actionable goals, we also collected their feedback on content validity (e.g., clarity, comprehensiveness, terminology) and feasibility (e.g., ability to collect needed information and data, time required). We describe refinements made to improve the assessment and streamline the process. The EQBMED program will deploy the assessment across various site types (e.g., FQHCs, safety net hospitals) and make further refinements as warranted.

Conclusions: Strategic investment in clinical trial diversity requires structured assessment of site maturity as a starting point for collaborative action. We propose the EQBMED maturity model as a first step toward informing efforts to increase representation of diverse populations in clinical research.

Background: The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany.

Methods: We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence.

Results: The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach.

Discussion: BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care.

Trial registration: German Clinical Trial Register DRKS00028840. Registered on April 2022.

Background: Undifferentiated arthritis (UA) is a term used to describe patients with inflammatory arthritis that has not differentiated into a specific rheumatic disease. UA may be a pre-stage of rheumatoid arthritis (RA) or another inflammatory disease or remain undifferentiated, but a substantial proportion of patients may also achieve spontaneous remission. As UA may be an early presentation of RA, rheumatologists often start methotrexate (or another csDMARD) as early as possible. There are however very little data on the potential benefits of early DMARD treatment, and longitudinal data suggests that long-term outcomes such as physical functioning hardly improved in these patients in the past decades. In the I CEA trial, we investigate if it is beneficial to start early treatment with MTX or baricitinib, a more rapidly acting drug with a broader mechanism of action, compared to waiting for spontaneous remission with symptomatic therapy in patients with UA.

Methods: The I CEA is a multicenter single-blind (independent assessor) randomized clinical trial with a 3-month interventional and 9-month observational follow-up period. The study includes patients with early (< 1 year symptom duration) DMARD-naïve undifferentiated arthritis. Patients with an increased risk of AEs with baricitinib treatment are excluded. Participants are randomized 1:1:1 to (1) symptom relief with NSAIDs and a single injection of glucocorticoids and (waiting for spontaneous remission); (2) methotrexate and a single injection of glucocorticoids, and NSAIDs are optional; and (3) baricitinib and a single injection of glucocorticoids and NSAIDs are optional. During the observational follow-up period, patients are treated in shared decision with their rheumatologist. The primary outcome will be the change in DAS at 3 months. Secondary outcomes include radiographic progression, physical functioning, patient-reported outcomes, cost utilities, safety, progression to classifiable RA, and disease activity over time.

Discussion: The 12-month I CEA trial studies early treatment of patients with UA with methotrexate, baricitinib, or NSAIDs. The study initially had a more complex design. Emerging safety warnings about baricitinib necessitated adjustment of the trial protocol including more extensive exclusion criteria. The number of included patients was lower than initially planned, supported by an updated sample size calculation.

Trial registration: Dutch trial register NL73202.058.20, EudraCT 2019-004359-35, registered 10-06-2020. Protocol version 1Q, 06-05-2024.

Introduction: Chronic kidney disease (CKD) is a pervasive disease of the current century that usually affects the adult population, especially people with diabetes and hypertension. According to the recent studies, inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction are determining risk factors in the pathogenesis of CKD. Melatonin as a strong antioxidant is produced in various tissues including the kidneys. The present clinical trial aims to examine the efficacy of melatonin supplementation on metabolic parameters, oxidative stress, and inflammatory biomarkers in diabetic patients with CKD.

Methods: This is a double-blind, randomized, placebo-controlled clinical study that will be investigated the impacts of melatonin supplementation in diabetic patients with CKD. Laboratory findings will be applied to diagnose diabetic CKD. Forty-eight eligible diabetic subjects with CKD will be selected and randomly assigned to receive 5 mg melatonin tablets or identical placebo twice daily for 10 weeks. Participants will be asked to remain on their usual diet and physical activity. The primary outcome of this study is changes in oxidative stress and inflammatory biomarkers. The secondary outcomes include changes in lipid profile, renal function indicators, fasting blood sugar and serum insulin, systolic and diastolic blood pressure (SBP and DBP), serum phosphorous concentration, sleep quality, body weight, body mass index (BMI), and waist circumference (WC). Statistical analysis will be conducted using the SPSS software (version 25).

Discussion: We hypothesize that melatonin administration may be useful for treating diabetic CKD by modulating oxidative stress, inflammation, regulating lipid metabolism, and increasing insulin sensitivity through different mechanisms. The current trial will exhibit the effects of melatonin, whether negative or positive, on diabetic CKD status.

Ethical aspects: The current trial received approval from Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.SHARIATI.REC.1402.072).

Trial registration: This study had been registered in Iranian Registry of Clinical Trials.

Registration number: IRCT20170202032367N9 on 11 August 2023. https://www.irct.ir/trial/70709 .

Background: The SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions.

Methods: This international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information.

Discussion: If the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology.

Trial registration: The trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022.

Background: New treatment approaches are urgently needed to improve the prognosis of children and adolescents with anorexia nervosa (AN). Recently, the feasibility of multidisciplinary home treatment that strongly involves the patients' parents/caregivers has been investigated. However, no RCT has yet been performed to test the efficacy and safety of this approach compared to standard treatment approaches, such as inpatient treatment.

Methods: In this multicenter randomized-controlled trial, home treatment for children and adolescents with AN aged 12 to 18 years is established at 5 major treatment centers for AN in Germany. Approximately 240 patients who are admitted to the hospital for AN will be included in the trial. After a short inpatient somatic stabilization phase (5-8 weeks), patients are randomized to receive either treatment as usual (TAU), in the form of continued inpatient or day patient treatment, or the newly developed home treatment (HoT) (n = 82/arm, n = 164 in total). There are three assessments throughout treatment (admission, randomization, and discharge), as well as follow-up assessments at 9 and 12 months after admission. The BMI at 12 months after admission (primary outcome) is compared between groups (adjusted for premorbid BMI and admission BMI); secondary outcomes include eating disorder and general psychopathology, the number and duration of psychiatric rehospitalizations, quality of life, motivation for treatment and treatment satisfaction. Other secondary outcomes include the primary caregivers' burden and skills in handling the child's illness and direct treatment costs. Statistical analysis will be based on intention-to-treat principles, using mixed models for repeated measures. (Serious) adverse events are assessed throughout treatment. In addition, the feasibility and implementation of HoT as well as the satisfaction and workload of the members of the multidisciplinary treatment teams in both arms will be assessed.

Discussion: In the case of a positive evaluation, HoT can be considered an effective treatment method to replace or complete established treatment methods, such as IP, for treating AN in children and adolescents. The home treatment setting might shorten inpatient stays in this patient group, increase treatment satisfaction, and help to reduce the risk of rehospitalization, which is associated with a better outcome in this vulnerable patient group.

Trial registration: The trial was registered with the German Clinical Trial Register (DRKS) under the ID DRKS00025925 on November 26, 2021 (prospectively registered): https://drks.de/search/de/trial/DRKS00025925 .

Background: Erector spinae plane block (ESPB) is a promising technique for effective analgesia. It is still uncertain if ESPB offers the same opioid-sparing effect as thoracic paravertebral block (PVB) in midline incision for upper abdominal surgery.

Methods: The study is a prospective, bi-center, randomized, controlled, non-inferior trial. One hundred fifty-eight patients scheduled for upper abdominal surgery will be randomly assigned to receive bilateral ESPB or PVB before surgery. The primary outcome will be the equivalent cumulative analgesia dosage of sufentanil during the surgery, which is defined as the total dosage of sufentanil from anesthesia induction to tracheal extubation. The main secondary outcomes include postoperative complications and the quality of recovery-15 score at 24 h, 48 h, and 30 days after surgery.

Discussion: This study will assess the opioid-sparing efficacy of ESPB and PVB, complications, and the quality of recovery of two blocks.

Trial registration: ChiCTR2300073030 ( https://www.chictr.org.cn/ ). Registered on 30 June 2023.

Objective: The objective of this study was to establish a zone of clinical equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial, which will compare resection and endoprosthetic reconstruction to internal fixation for skeletal metastases of the proximal femur.

Methods: A survey was developed, piloted, and distributed to self-declared interested stakeholders in the PERFORM trial. The survey targeted orthopedic oncologists and was designed to assess patient and bone lesion characteristics that drive surgical decision-making in the treatment of skeletal metastases in the proximal femur. An Ethics Waiver was obtained at the lead academic institution and data was collected in the REDCap survey database.

Results: Responses were complete from 76 surgeons across North America, South America, Europe, Asia, and Africa. Response rate from self-declared interested stakeholders was 70%, with additional responses collected from a broader international audience. Responses indicate that a study population for which either resection and endoprosthetic reconstruction or internal fixation are acceptable options include (1) life expectancy at least 6 months, (2) bone loss of no more than 75% and no less than 25%, and (3) minimal to moderate risk for perioperative complications. Ninety-three percent of respondents indicated that they would be interested in participating in the PERFORM trial.

Conclusion: A preliminary zone of equipoise for the PERFORM trial includes patients with 25-75% bone loss, low to moderate risk of operative complications, and life expectancy of at least 6 months. Further stakeholder discussions have finalized the PERFORM trial protocol prior to study initiation.