Bad Nauheim

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 aromatase inhibitor (AI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the current effective local 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 current effective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + AI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + AI ± 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 Austrian 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 + AI ± 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.

Axial spondyloarthritis (axSpA) is an immune-mediated inflammatory disease primarily affecting the axial skeleton. The most frequent axSpA symptom is chronic, often inflammatory back pain that might be difficult to distinguish from other causes of chronic back pain. Many participants report persistent pain, including back pain, which impacts disease activity and and impairs quality of life while evoking typical disease burden such as sleep disturbance, social isolation, loss of productivity, as well as anxiety and depression. This study will assess the real-world effectiveness of upadacitinib on early and sustained disease control, and the association between pain and clinical/patient-reported outcomes in axSpA participants. Upadacitinib is being developed for the treatment of axSpA. Approximately 352 adult participants with active axSpA will be enrolled in Germany. Participants will receive oral upadacitinib tablets as prescribed by the physician prior to enrolling in this study in accordance with the terms of the local marketing authorization and professional and reimbursement guidelines with regards to dose, population and indication. The overall duration of the study is approximately 52 weeks. There may be a higher burden for participants in this study compared to usual standard of care due to study procedures. Participants will attend regular visits per routine clinical practice. The effect of the treatment will be checked by medical assessments, checking for side effects, and questionnaires.

The purpose of this multicenter, randomized, placebo-controlled and double-blind study is to evaluate the efficacy and safety of subcutaneous anifrolumab compared with placebo on the overall disease activity in participants with moderate to severe Idiopathic Inflammatory Myopathies (IIM) \[polymyositis (PM) or dermatomyositis (DM)\] while receiving standard of care (SoC) treatment.

This is a prospective, multicenter, open-label, randomized trial comparing OAC with no OAC (1:1 ratio) in patients who develop new-onset POAF after CABG. The primary effectiveness endpoint is the composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (VTE) at 90 days after randomization. The primary safety endpoint is BARC (Bleeding Academic Research Consortium) grade 3 or 5 bleeding at 90 days after randomization. The overall intent is to evaluate the trade-off in prevention of thromboembolic events versus an increase in bleeding. Patients will be randomly assigned to the following treatment strategies: * OAC-based strategy (experimental arm): OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant (apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) * Antiplatelet-only strategy (control arm): single antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) The protocol-specified duration of anticoagulation is 90 days. Patients, who are randomized to the control arm and develop recurrent AF after 30 days, may be crossed-over to an OAC. Accrual is expected to take 60 months. Study follow-up visits will be performed at 90 days and phone follow-up at days 30, 60, and 180 days. Data for patients enrolled in the registry will be ascertained from the local clinical site via a review of medical records. The baseline risk profile of registry patients (i.e., patients eligible but unwilling to be randomized) will be analyzed and compared to that of patients randomized in the trial. The usage of anticoagulant and antiplatelet therapies in the registry population overall and baseline CHA2DS2-VASC ischemic stroke risk score will also be determined. Up to 500 patients will also be offered the option to participate in a digital health substudy which includes a wearable heart rhythm monitor device for 30 days post discharge.

The complete revascularization versus culprit lesion only PCI in NSTEMI (COMPLETE-NSTEMI) trial aims to investigate whether multivessel complete PCI is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel coronary artery disease.

The MANTRA Master Plan (Master Protocol) is intended as an overarching Umbrella Protocol that allows multiple substudies to be added, as needed. The Umbrella Master Protocol concept offers an excellent solution to provide post-marketing clinical follow-up information on the entire cardiac surgery heart valve portfolio of the sponsor in a common database. Currently, three substudies are planned: * MANTRA - Aortic Sub-Study * MANTRA - Mitral/Tricuspid Sub-Study (excluding Memo 4D) * MANTRA - Memo 4D Sub-Study The aim of the studies assembled under the master protocol is the continued collection of safety and performance data during heart valve procedures and the relevant follow-up visits in subjects where any of the CORCYM devices and accessories are used in a real-world setting, in accordance with the IFUs, and at the discretion of the investigator. MANTRA study is expected to enroll approximately 2150 subjects in up to 130 sites worldwide: * Approximately 1650 subjects considered suitable for treatment with a CORCYM aortic device * Approximately 300 subjects considered suitable for treatment with a CORCYM mitral and/or tricuspid device (excluding Memo 4D) * Approximately 200 subjects considered suitable for treatment with Memo 4D Expected enrollment duration may vary across the different projects. Subject follow-up is planned at discharge, 30 days after implantation and then annually up to 10 years. Sites can choose to participate in one or more sub-studies. All available data shall be gathered during standard medical care. At a minimum, the following data will be collected: * Informed Consent * Screening/Baseline data, including demographics and medical history * Procedural data * Hospitalization and Discharge data * Follow-up data: 30 days and annually up to 10 years post procedure * Serious Adverse Event and Device Deficiencies information As part of the study, the subject will be asked to complete quality of life questionnaire(s) at baseline, 30 days and at 1-year follow-up. In addition, for the MEMO 4D sub-study only, an Echocardiography Core Laboratory has been appointed by the Sponsor to assess the hemodynamic and structural performance, annular motion and dynamics, and 3D echocardiogram images (transesophageal during the procedure and transthoracic during follow up) will be collected for Corelab readings.

Takotsubo syndrome (TTS) has been suggested to be caused by catecholamine excess with myocardial inflammation-enhanced cardiac injury. Substantial morbidity and mortality have repeatedly been reported, even though reduced ejection fraction frequently recovers spontaneously. So far there is no evidence-based treatment available. In a clinically relevant mouse model of catecholamine-driven TTS, cyclosporine A (CsA) bolus therapy markedly improves outcome, likely mediated via suppression of calcineurin-driven inflammation. The investigators have thus designed a pilot multicentre randomized controlled trial (RCT) to investigate the impact of repetitive CsA bolus therapy vs. placebo in acute TTS patients with an increased risk of intrahospital complications and a 32% estimated 5-year mortality. As primary outcome myocardial damage will be compared between groups via high-sensitive Troponin T plasma area under the curve (AUC). Recovery of cardiac function, the extent of myocardial oedema at 72h, length of hospital-stay, 30-day-, and 1-year composite clinical outcome as well as psychosocial and quality of life self-assessment will be secondary endpoints. The results of this trial may reveal CsA as a first pathophysiology-driven treatment option of TTS and enable a phase III follow-up trial with outcome parameters as primary endpoint.

Preoperative anxiety and stress are risk factors for postoperative delirium (PD), postoperative cognitive decline (POCD), morbidity, and mortality. The primary objective of this study is to reduce the preoperative stress response through the combined presentation of a virtual reality environment with natural landscape and binaural beats. The proposed study is a monocenter, 5-arm prospective randomized controlled intervention of 125 patients undergoing elective cardiac surgery using extracorporeal circulation. A 360 ° video sequence including natural sounds (with and without binaural beats) are presented to 2 groups, and 2 groups receive only natural sounds (with and without binaural beats); a group without stimuli (standard procedure) represents the control group. On the day of admission to the acute care clinic, a detailed examination of neuropsychological functions and health-related quality of life (HQL) is scheduled. Cortisol-saliva, heart rate variability and electrodermal activity as indicators for stress and relaxation are measured during the intervention phase (duration: approximately 30 minutes), which leads directly into the narcosis phase. To investigate postoperative neurocognitive dysfunctions, daily delirium screenings will be performed after surgery, and a neuropsychological examination will be performed at the time of discharge from the acute hospital and at 3 months after surgery. Changes in HQL will also be completed at 3 months post-surgery.

This study is conducted as a non-clinical substudy within the DESTRESS research program (Decreasing preoperative stress to prevent postoperative delirium and postoperative cognitive decline in cardiac surgical patients: A randomized controlled trial on relaxation interventions via virtual reality and binaural beats; NCT05036538). In contrast to the main clinical trial, which investigates cardiac surgical patients, this study focuses on non-clinical adult participants who are not undergoing medical or surgical treatment and are not enrolled as patients of the Kerckhoff-Clinic Bad Nauheim (Germany). The purpose of this substudy is to examine the effects of relaxation interventions under controlled conditions, independent of disease-related, perioperative, or pharmacological confounding factors. The results are intended to provide a reference framework for interpreting and contextualizing findings from the clinical DESTRESS trial. Participants are randomly assigned to one of five experimental conditions: (1) natural soundscapes, (2) natural soundscapes combined with binaural beats, (3) virtual reality-based natural environments, (4) virtual reality-based natural environments combined with binaural beats, or (5) a control condition without any relaxation intervention. Each participant completes a single session lasting approximately 30 minutes. During the intervention or control condition, physiological parameters, including heart rate variability and electrodermal activity, are continuously recorded using non-invasive sensors. Neurocognition and subjective stress levels are assessed using standardized tests and self-report questionnaires administered before and after the session. This study aims to evaluate the feasibility, acceptability, and preliminary efficacy of virtual reality- and audio-based relaxation interventions in a non-clinical population. The findings are expected to contribute to a better understanding of the mechanisms and generalizability of stress-reduction approaches and to inform the interpretation of outcomes in the overarching DESTRESS research program.

The VANTAGE clinical trial will evaluate the safety and effectiveness of the Navitor valve in patients with severe, symptomatic aortic stenosis who are at intermediate or low risk of surgical mortality. This trial will also evaluate the safety and effectiveness of the Navitor valve in a valve-in-valve application.