Aurora De Chile 9872 - San Ramã³n, Chile

Impact of Stress on Cardiovascular Events in Patients with Peripheral Arterial Disease

Based on World Health Organization data, atherosclerotic cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Peripheral arterial disease (PAD) is a poly-vascular disease in multiple arterial beds mostly associated with high atherosclerotic burden. It is estimated that around 50 million people in Europe alone suffer from PAD and the prevalence increases with age. The cause of CVD, such as PAD, coronary artery disease (CAD) or cerebrovascular disease, is atherosclerosis, a systemic chronic inflammatory vascular disease. Patients with CVD are at increased risk of life-threatening complications such as acute limb events, stroke and myocardial infarction combined with an impaired quality of life. Acute and chronic stress affect the cardiovascular system. Numerous studies have shown the relationship between chronic stress and cardiovascular diseases. On the one hand, permanent negative stressors lead to cardiovascular diseases via different pathways such as the hypothalamic-pituitary-adrenal (HPA) axis or the autonomic nervous system, and, on the other hand, stress can aggravate an already existing CVD. In addition, cardiovascular risk factors like hypertension and hypercholesteremia are negatively influenced by stress. Stress as a cardiovascular risk factor is receiving increasing attention, leading to its recognition in current guidelines on cardiovascular disease prevention. Due to the demographic development of an ageing population and the simultaneous increase in atherogenic risk factors, a further rise of patients with CVD will be expected in the future. Thus, sufficient assessment of cardiovascular risk in patients with PAD and adequate stress evaluation are elementary. However, there is a lack of consensus about the definition and measurement of stress. Therefore, the investigators aim to evaluate and compare the efficiency of different stress measuring methods depending on the occurrence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD.

SmartWatch-driven AF Detection in Stroke Patients

Patients with established continuous ICM monitoring from the prospective, randomized, multicenter study Find-AF 2 (NCT04371055) are recruited for this trial. Find-AF 2 is being carried out at Leipzig University Hospital since 2020 with the help of about 50 study centers throughout Germany. The AppleWatch Series 10, a device from the current market leader, was chosen because extensive data from clinical trials is already available and data regarding the market leader has particular societal relevance. The AF detection algorithm is based on photoplethysmography (analysis of the pulse current curve) and semicontinuous monitoring. If a rhythm irregularity is detected during hourly measurements, the measurement interval is shortened. If this finding is confirmed in several consecutive measurements, the user is notified. In this pilot study, patients are trained to record a 30-second ECG with the AppleWatch in the event of notification. This is done by placing the other hand on the crown of the watch. The report will then be transmitted. The AppleWatch must be paired with another Apple device (e.g. iPhone) to use the ECG app and must be charged daily (battery life 18 hours). Our patients are provided with an iPhone for study use and are trained in using the AppleWatch. The AppleWatch is not certified as medical device, but the ECG data collected by the AppleWatch will be used for research purposes only and not for therapeutical or diagnostical purposes. The second wearable will be the PulseOn device. The battery lasts over two weeks. No additional device is needed for writing an ECG. AF screening is also performed photoplethysmographically. In the case of detection of an arrhythmic pulse curve, this is communicated by vibration. By laying the other hand on the device, a 1-channel ECG is performed for registration. Regular data transfer is done at the patient's home via a gateway device to the PulseOn server. The Core lab will monitor the data transmission. Although PulseOn is a certified medical device, the ECG data collected by the PulseOn device will be used for research purposes only and not for therapeutical or diagnostical purposes. The ICM is the gold standard for recording relevant arrhythmias.

A Non-interventional Study for Kisqali (Ribociclib) in Combination With an Aromatase Inhibitor for Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer at High Risk of Recurrence

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an non-steroidal aromatase inhibitor (NSAI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the German summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the respective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + NSAI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + NSAI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and optionally Austrian and Swiss breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + NSAI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

Adjusted High-dose Chemotherapy with Autologous Stem Cell Transplant Vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. However, there are alternative treatment approaches to consider with the potential to improve medical outcomes for this patient population. The current standard of care in Germany and many international centres for patients 65 and older is treatment with R-MP, comprising rituximab, high-dose methotrexate (HD-MTX) and procarbazine followed by maintenance therapy with procarbazine. An alternative approach comprised of a shorter induction treatment with rituximab, HD-MTX and cytarabine (MARTA) followed by age-adjusted high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) was recently shown to be feasible and effective in elderly PCNSL patients considered eligible for high-dose chemotherapy requiring autologous stem cell transplantation. Nevertheless, data evaluating this short duration treatment approach remains scarce, and randomized trials have not yet been published. The objective of the PRIMA-CNS trial is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with R-MP followed by maintenance with procarbazine in elderly patients with newly diagnosed PCNSL; not only regarding survival and remission after treatment but also regarding standards like quality of life (QOL) and treatment related morbidities. Results of this randomized trial will either change the standard of care to an intense and shorter treatment approach or re-define R-MP as a proven treatment standard. In addition, a geriatric assessement is implemented in this trial with the goal to better define transplant eligibility. If this trial shows the superiority of HCT-ASCT, the investigators will establish an improved treatment standard with increased chances for long-term remission and cure and reduced frequency and length of chemotherapy treatment. Considering the poor prognosis of this patient population, this randomized phase III trial is of great clinical importance to provide patients, the patients' families and care takers with optimal treatment.

A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

Audio Hypnosis for Reducing Anxiety in Children and Adolescents Undergoing MRI: A Randomized Controlled Trial

Study Overview This is a randomized controlled trial (RCT) investigating the effectiveness of an audio hypnosis intervention in reducing pre-procedural anxiety in children and adolescents (ages 6-14) undergoing an MRI examination without sedation. The study will compare an intervention group (receiving access to an audio hypnosis recording) with a control group (receiving standard pre-MRI explanations) to assess whether the hypnosis audio reduces anxiety levels, improves patient cooperation, and minimizes scan interruptions or movement artifacts. The study is monocentric, conducted at the Elisabeth Hospital Essen, Department of Pediatric Medicine, and aims to enroll 100 participants (50 per group). Study Design - Type: Randomized, controlled, single-center interventional study - Intervention: Audio hypnosis via a digital recording ("Ellis Traumgeschichte") accessible via QR code - Control: Standard pre-MRI information provided by medical staff - Sample Size: 100 participants (50 per group) - Study Duration: Recruitment period of up to 24 months, with the total study duration extending until data analysis is complete - Intervention Duration: The hypnosis audio lasts approximately 20 minutes and can be listened to multiple times before the MRI scan Intervention and Data Collection Participants will be randomly assigned to one of two groups: - Intervention Group: Receives a flyer with a QR code linking to a hypnosis audio recording, which they can listen to as often as they wish before their MRI scan. - Control Group: Receives standard verbal and written pre-MRI information from medical staff without additional hypnosis intervention. - Both Groups: Undergo their scheduled MRI scan and receive routine medical counseling. Data Collection Time Points: - T0 (Baseline): - Participant enrollment, informed consent, and randomization - Distribution of hypnosis audio (intervention group only) - T1 (Before MRI): - Self-reported anxiety assessment using the KAT III questionnaire - Parent-reported anxiety assessment using a visual analog scale (VAS) - T2 (During MRI): - Recording of scan interruptions - Noting if the MRI scan was terminated early - Presence of motion artifacts on MRI images - T3 (After MRI): - Retrospective self-reported anxiety assessment using KAT III - MRI technologist's anxiety assessment using VAS Registry and Data Quality Assurance Measures Although this study is not a formal patient registry, strict data quality control measures will be implemented to ensure the accuracy and reliability of collected data: 1. Quality Assurance Plan: - The study will adhere to Good Clinical Practice (GCP) guidelines, with regular monitoring and documentation audits. - Data validation checks will be applied to ensure consistency in reported anxiety levels across time points. - Any protocol deviations will be recorded and evaluated. 2. Data Validation and Range Checks: - Automated range checks will be implemented to detect inconsistencies in questionnaire responses (e.g., unrealistic changes in anxiety scores). - Manual verification of data entries will be performed by research staff. 3. Source Data Verification (SDV): - Randomly selected data entries will be compared with original records (e.g., consent forms, MRI technologist logs) to ensure accuracy. - Adherence to protocol-defined randomization procedures will be confirmed. 4. Data Dictionary: - Variables include demographic data, anxiety scores (KAT III, VAS), scan interruptions, and MRI completion rates. - Standardized coding and response scales (e.g., VAS range 0-10) will be used to maintain consistency across participants. 5. Standard Operating Procedures (SOPs): - Detailed SOPs will be followed for patient recruitment, randomization, intervention administration, data collection, and adverse event monitoring. - Adverse events, though unlikely, will be recorded and reported according to ethical guidelines. 6. Sample Size Assessment: - Based on literature data, a medium effect size (Cohen's d = 0.60) was assumed for pre-MRI anxiety reduction. - 90 participants (45 per group) are required to achieve 80% power at α = 0.05 using a two-sided t-test. - To account for a 10% dropout rate, 100 participants will be enrolled (50 per group). 7. Handling of Missing Data: - Missing questionnaire responses will be managed using multiple imputation techniques via the Markov Chain Monte Carlo (MCMC) method. - Sensitivity analyses will be performed to assess the impact of missing data on study conclusions. 8. Statistical Analysis Plan: - The primary hypothesis (anxiety reduction in the intervention group) will be tested using a two-sided t-test with a significance level of α = 0.05. - Secondary outcomes will be analyzed using linear mixed models to account for repeated measures. - The intention-to-treat (ITT) principle will be applied to all analyses. - The potential mediation effect of reduced anxiety on MRI scan success (fewer interruptions, better image quality) will be explored using regression models. Risk and Benefit Assessment - Potential Benefits: - Reduction of MRI-related anxiety in children without the need for sedation - Potential for fewer MRI scan interruptions and better image quality - Non-invasive, low-cost, and easily scalable intervention - Potential Risks: - Minimal risks, comparable to standard relaxation techniques - Some participants may experience mild side effects (e.g., dizziness, headache) Ethical and Regulatory Considerations - Ethical approval: The study was approved by the Ethics Committee of Witten/Herdecke University - Informed Consent: - Participants and their parents will receive detailed study information and provide written informed consent. - Withdrawal from the study is possible at any time without consequences. - Data Protection: - All study data will be pseudonymized to protect participant confidentiality. - Data will be stored in secure, access-controlled databases and used exclusively for research purposes. Funding and Sponsorship - The study is not externally funded. - The development of the hypnosis intervention and study materials was supported by Ellis Freunde, a non-profit organization. - No financial conflicts of interest exist for the study investigators. Conclusion This randomized controlled trial aims to provide scientific evidence on the effectiveness of audio hypnosis as a simple, non-pharmacological intervention to reduce MRI-related anxiety in children and adolescents. The study incorporates rigorous data quality assurance measures, follows GCP-compliant protocols, and implements a robust statistical analysis plan to ensure reliable and meaningful results.

An Extension and Crossover Vaccination Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus Given to Adults 60 Years of Age and Above Who Participated in RSV OA=ADJ-006 Study

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

A Non-interventional Study Evaluating Clinical Utility and Implications on Improved Patient Management of Serum Neurofilament as a Prognostic Marker for Disease Activity in Patients With Relapsing Multiple Sclerosis

Prospective, primary data will be collected from patients with sNfL outcomes in the context of switching to ofatumumab or continuing their current therapy. Data collection will cover a maximum period of 24 months. The observational period will not be dictated by the protocol. Baseline and follow-up visits will take place at a frequency defined as per Investigator´s discretion following clinical routine. The diagnostic or monitoring procedures are only those ordinarily applied to therapeutic strategy and routine clinical care. During the observation phase of the study, data will be collected according to standard of care as recommended by KKNMS (Competence Network Multiple Sclerosis in Germany). Eligible participants for the study are patients who have received treatment with category 1 DMTs and those who have included sNfL into their treatment decision-making process. These patients have the option to either continue their current DMT or switch to ofatumumab. According to local treatment guidelines, DMT category 1 include dimethylfumarate/diroximelfumarate, glatirameroids, Interferon beta and teriflunomide. The decision to switch to ofatumumab or to continue the current DMT category 1 therapy must be made by the treating physician independently of the decision to enroll the patient in the study.

Efficacy, Safety, and Tolerability of Once Daily Oral Administration of AZD5004 Versus Placebo for 26 Weeks in Adults With Type 2 Diabetes Mellitus.

This is a Phase IIb, randomised, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of AZD5004 in adults with type 2 diabetes mellitus, compared to placebo and active comparator. The study is planned to be conducted in approximately 15 countries, approximately 90 sites will be involved.