Shih Lin Taipei 111, Taiwan

A Study to Investigate the Efficacy and Safety of Tezepelumab in Adult Participants With Moderate to Very Severe COPD (D5241C00007)

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving inhaled maintenance therapy and having had at least 2 moderate, or 1 severe, COPD exacerbations in the 12 months prior to Visit 1. Subjects will receive monthly subcutaneous injection of one of two different doses of tezepelumab, or placebo, with a maximum treatment duration of 76 weeks and a minimum of 52 weeks. The study also includes a off-treatment safety follow-up period of 12 weeks.

Supplemental High Flow Oxygen to Reduce Infections in Obese Gynecological Cancer Patients

This study aims to investigate the prophylactic value of postoperative oxygen administration against the development of wound infections in obese gynecological oncology patients undergoing laparotomy for the treatment of endometrial or ovarian cancer. At the same time, the factors that lead to an increase in this risk will be outlined.

Digestive Enzyme Formulation Intervention in IBS Patients Who Previously Clinically Responded to Mediterranean LFD

IBS patients who participated in a two-arm clinical trial (ClinicalTrials.gov ID: NCT03997708) and responded to the Mediterranean Diet Adjusted Low FODMAP (MED-LFD) Diet will be considered eligible if their symptoms recurred one year after their initial response to the dietary intervention. Among them, patients without any or mild symptoms, defined as IBS severity scoring system (IBS-SSS) ≤ 175, will be excluded. Moreover, subjects who were randomized to the MED-LFD arm in the previous study, but could not adhere to the dietary intervention, will be included too. A jar containing the digestive enzymes in the form of powder will be provided to each patient at the start of the study. Patients will be instructed to use the powder formulation according to manufacturer instructions for 1 month. To assess compliance, the weight of each jar will be measured both at the initiation and the end of the study. Patients will also be asked on three different days (one day from the weekend), to estimate the average number of meals per day. Due to the limited sample size (54 patients who received the MED-LFD diet in the previous phase will be screened for eligibility), a control group will be omitted. To reduce the placebo effect, patients will be misinformed that half will take a placebo formulation, randomly. All patients will be thoroughly trained regarding the proper consumption of the powder (exact dose, timing, etc.), through personal training, videos, leaflets, and other type of training materials.

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

Investigation of the Effect of muSic on the Stress of Preterm neONates Through innovATive Applications (SONATA)

Study Design In this prospective randomized controlled clinical trial, live born preterm neonates should have a stable clinical status at the time of study enrollment and therefore it is likely that some neonates will be enrolled after 5-7 days of admission. The allocation of neonates will be randomized in order to equalize the prognostic factors (confounding factors) between the groups. By using sequentially numbered envelopes, participants will be assigned to either intervention or control group by simple random allocation. In this way, researchers will avoid resulting in an unequal number of participants between the two groups. Researchers after obtaining parental informed consent, will request a sealed envelope from a staff member not involved in the study. The envelope will be opened and the allocation will be documented on a list, and signed by a member of the research team and a staff member as witness. Participants The study will recruit preterm neonates. It has been estimated that with a sample of 35 neonates per group, the study will have more than 85% power to find differences in biomarkers between the intervention and control group, with an effect size equal to or greater than 0.72 and a significance level of 0.05. Music Intervention Neonates will be placed in a closed incubator whose acoustic properties have been previously studied. Under the close surveillance of a team member, monitor alarms will be also silenced so as to decrease exposure to sudden and unpleasant auditory stimuli during music intervention. A mini portable speaker will be settled inside the incubator in appropriate conditions (volume level, distance e.t.c) for safety reasons. Neonates allocated to the intervention group will be exposed to a specific piece of music, 30 minutes after feeding (if oral feeding exists), for a duration no more than 30 minutes that will be indicated from the certified music - therapist, experienced in working with preterm infants. A questionnaire created by the research team will be administered to parents in order to investigate the neonate's prenatal exposure of music (as a fetus). Data collection Biomarkers Salivary samples will be obtained from preterm neonates via salivette swabs. The polyester filter of the device will be partitioned into equal sections under sterile conditions to account for the small oral size of the neonates. One sample will be obtained before the music intervention and one sample 60 minutes after the music intervention, considering diurnal flow patterns. Saliva sampling is unlikely to cause stress or pain to the neonate. In the control group only one sample per day will be obtained within the same time period with the intervention group. Sample collection will be repeated in the same way everyday for 5 consecutive days. Each sample will be obtained before any stressful intervention (e.g. blood sampling, weighing, bathing, etc.). Furthermore, it is important to note that no other procedure that may reduce stress will take place simultaneously with music intervention (i.e. kangaroo care, gentle touching e.t.c) in order to interpret the effect of music more precisely. Saliva samples will be centrifuged very soon after collection and stored at -80oC until the laboratory analyses are performed. Measurements will be performed with cobas e411 automated analyzer or through ELISA.

SCAD : a Registry of Spontaneous Coronary Artery Dissection

Observational, multicentre, international retrospective and prospective cohort study. Since this is an observational study, a formal sample size is not necessary. At least 500 prospectively recruited patients and 500 historical cases will be enrolled. Patient data will be collected at the following time-points: - First SCAD event visit (retrospectively on chart review) - First follow-up: at time of enrolment - Yearly follow-up: up to 1, 2, 3, 4 and 5 years post enrolment or until study completion Approximately 30 countries and 120 sites will participate in this registry.

Genomic and Methylation Markers in SCLC and LCNEC for Chemo-Immunotherapy Resistance Prediction (STRATUS)

The STRATUS Trial (Study of Tumor Characteristics and Molecular Signatures in Neuroendocrine Tumors and SCLC) is an ambitious, prospective observational study designed to explore the molecular and genomic mechanisms underlying resistance to chemo-immunotherapy in patients diagnosed with extensive-stage small cell lung cancer (ES-SCLC) and metastatic large cell neuroendocrine carcinoma (LCNEC). These two aggressive forms of cancer represent a significant unmet clinical need, with high relapse rates and limited therapeutic options available following the development of treatment resistance. The study seeks to uncover actionable biomarkers, characterize resistance mechanisms, and improve our understanding of tumor evolution under selective pressures from standard therapies. By leveraging cutting-edge molecular techniques, such as next-generation sequencing (NGS), DNA methylation profiling, and liquid biopsies, STRATUS aims to set the foundation for personalized cancer treatment approaches in these difficult-to-treat malignancies. Background and Rationale The Challenge of Resistance in ES-SCLC and LCNEC Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are both high-grade neuroendocrine tumors characterized by rapid growth, early dissemination, and a poor prognosis. Approximately two-thirds of SCLC cases are diagnosed as extensive-stage disease (ES-SCLC), where the tumor has spread beyond the hemithorax and regional lymph nodes. Similarly, LCNEC, though rare, is frequently diagnosed at metastatic stages, with limited systemic treatment options available. Standard treatment for ES-SCLC includes platinum-based chemotherapy combined with immune checkpoint inhibitors (ICIs), such as atezolizumab or durvalumab. While initial response rates exceed 70%, resistance develops rapidly in most patients, leading to disease progression within months. For LCNEC, the therapeutic landscape is even more limited, with a lack of targeted therapies or predictive biomarkers guiding treatment. Need for Molecular Insights Resistance mechanisms in these cancers are thought to involve tumor heterogeneity, clonal evolution, epigenetic modifications, and immune evasion. However, the exact processes that drive resistance remain poorly characterized. Molecular profiling offers an opportunity to identify genomic and epigenetic alterations that correlate with treatment failure, allowing for the development of predictive biomarkers and targeted therapeutic strategies. Role of Liquid Biopsies Liquid biopsies, including the analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), have emerged as powerful tools for non-invasive tumor monitoring. These biomarkers provide real-time insights into tumor dynamics, enabling the detection of resistance mechanisms, clonal evolution, and molecular relapse. Study Objectives Primary Objective To identify and characterize genomic, epigenetic, and methylation signatures associated with resistance to chemo-immunotherapy in ES-SCLC and LCNEC patients. Secondary Objectives To evaluate the relationship between circulating biomarkers (CTCs, ctDNA) and clinical outcomes, including progression-free survival (PFS) and overall survival (OS). To compare molecular profiles between long-term responders and patients who develop early resistance. To assess tumor-immune interactions and their role in resistance mechanisms, focusing on PD-L1 expression, T-cell exhaustion, and cytokine signaling pathways. Exploratory Objectives To investigate clonal evolution and emergent subpopulations associated with resistance using phylogenetic analyses. To explore spatial transcriptomic patterns within the tumor microenvironment. To evaluate the potential of novel biomarkers for guiding treatment decisions and monitoring disease progression. Study Design The STRATUS Trial is a multicenter, prospective observational study involving patients treated at the 3rd Department of Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, and other participating centers. The study includes detailed clinical, molecular, and imaging assessments over a three-year follow-up period. Inclusion Criteria Adults aged 18-85 years diagnosed with ES-SCLC or LCNEC. ECOG performance status of 0-2. Histological confirmation of diagnosis with available tumor tissue for molecular analysis. At least one measurable or evaluable lesion according to RECIST 1.1 criteria. Willingness to provide blood samples and participate in follow-up visits. Exclusion Criteria Inability to tolerate chemo-immunotherapy. Presence of another active malignancy or significant comorbidity. Patients with no measurable disease or inadequate follow-up potential. Data Collection and Sample Handling Baseline Assessments Before starting treatment, participants will undergo: Comprehensive clinical evaluations, including medical history, ECOG performance status, and comorbid conditions. Imaging studies (e.g., CT, PET) to assess tumor burden and metastatic sites. Blood sample collection for baseline ctDNA and CTC analysis. Tumor biopsies for genomic, transcriptomic, and methylation profiling. On-Treatment Monitoring Participants will attend follow-up visits every 9 weeks, during which: Blood samples will be collected to monitor ctDNA and CTC levels. Imaging studies will evaluate tumor response according to RECIST 1.1 criteria. Adverse events, clinical progression, and treatment modifications will be documented. Disease Progression Assessments For patients with progressive disease: Repeat biopsies of newly emerging lesions will be performed to identify resistance-associated changes. Blood samples will capture dynamic shifts in ctDNA and CTC profiles, enabling comparisons with baseline and on-treatment data. Laboratory Methods NGS-Based Genomic Analysis: Comprehensive sequencing will identify mutations, copy number alterations, and structural rearrangements. Epigenetic Profiling: DNA methylation arrays will uncover resistance-related epigenetic changes. Spatial Transcriptomics: High-resolution analysis of tumor microenvironment architecture and gene expression patterns. Statistical Analysis Sample Size A total of 111 patients will be enrolled, providing sufficient power to detect significant differences in molecular markers across subgroups. Primary Analysis Regression models will evaluate associations between molecular markers and treatment resistance. Descriptive statistics will summarize biomarker distributions and clinical outcomes. Secondary Analysis Kaplan-Meier survival curves will estimate PFS and OS. Cox proportional hazards models will assess the prognostic significance of identified biomarkers. Exploratory Analysis Machine learning models will predict resistance based on integrated multi-omic data. Clonal evolution will be modeled using phylogenetic techniques to trace tumor adaptation under therapeutic pressure. Ethical Considerations The study will comply with the Declaration of Helsinki and GDPR guidelines for data protection. Participants will provide written informed consent, and all data will be de-identified to ensure confidentiality. Significance and Anticipated Impact The STRATUS Trial is expected to: Identify actionable biomarkers for predicting and overcoming resistance. Advance the understanding of tumor evolution and immune evasion in SCLC and LCNEC. Guide the development of personalized treatment strategies, ultimately improving patient outcomes. Conclusion The STRATUS Trial represents a landmark effort to address the challenges of resistance in SCLC and LCNEC. By combining advanced molecular analyses with robust clinical monitoring, this study has the potential to transform the management of these aggressive cancers and pave the way for a new era of precision oncology.

A Real-World Study to Gain Clinical Insights Into Faricimab (FaReal Study)