Ahaus

The purpose of this study is to evaluate the efficacy, safety and tolerability of pelacarsen (TQJ230) administered subcutaneously once monthly compared to placebo in slowing the progression of calcific aortic valve stenosis.

This study is to assess the burden of disease in adolescent and adult participants with moderate or severe alopecia areata (AA), non-segmental vitiligo (NSV), or moderate to severe hidradenitis suppurativa (HS) in a large global real-world participant population.

The aim of the current study is to evaluate the effectiveness and safety of bempedoic acid combined with ezetimibe and either atorvastatin or rosuvastatin (hereafter defined as triple therapy) in a real-world clinical setting. No drug will be administered during this observational study. The primary objective of the study is to evaluate the effectiveness of the triple therapy in terms of LDL-C reduction at 8 weeks. The secondary objectives will include the following: * Goal attainment at 8 weeks and 1 year after start of triple therapy * Effectiveness of triple therapy in terms of LDL-C reduction at 1 year * Effectiveness of adding bempedoic acid to statin and ezetimbe at 8 weeks and 1 year * Effectiveness of adding bempedoic acid/ezetimibe FDC to statin in terms of LDL-C reduction at 8 weeks and 1 year * Changes in laboratory values at 8 weeks and 1 year after start of triple therapy * Adherence to triple therapy treatment * Collection and recording of all adverse events occurred since initiation of triple therapy * MACE-3 and MACE-4 (consisting of non-fatal MI, non-fatal stroke, CV-death, and coronary revascularization (for MACE-4 only)) during the year of follow-up * Treatment changes at LMT initiation and at triple therapy initiation * Treatment pathway from triple therapy initiation to 1-year after start of triple therapy

The purpose of this study is to evaluate the efficacy and safety of bimekizumab compared with placebo in participants with palmoplantar pustulosis (PPP).

BERING-MELANOMA - designed as a prospective, longitudinal, non-interventional study - investigates real-world effectiveness, quality of life, safety and tolerability of encorafenib plus binimetinib in unresectable advanced or metastatic BRAF(Rapidly Accelerated Fibrosarcoma isoform B)-V600-mutant malignant melanoma after commercial availability of these two products in Germany, Austria and Switzerland. The study focusses on the documentation of the first and second line setting (i.e. after one line of prior checkpoint inhibition) by documenting patients treated according to the SmPC (Summary of Product Characteristics).

Study Rationale and Clinical Significance The increasing demand for spectacle independence following cataract surgery has driven the development of advanced intraocular lens (IOL) technologies that extend beyond traditional monofocal designs. This prospective comparative study addresses a critical gap in understanding the real-world performance of contemporary extended depth-of-focus (EDOF) IOLs versus premium monofocal lenses. Intermediate Vision Focus: Modern lifestyle demands have elevated the importance of intermediate visual function, particularly for distances between 60-80 cm, which encompass critical daily activities including computer work, dashboard viewing, kitchen tasks, and tablet reading. Traditional monofocal IOLs inherently limit functional vision to a single focal distance, necessitating spectacle dependence for intermediate and near visual tasks. This study specifically evaluates how different optical approaches address this intermediate vision gap. EDOF Technology Principles: The study examines five distinct optical strategies for extending depth of focus: wavefront-shaping technology (AcrySof IQ Vivity), progressive power profiles (TECNIS Eyhance), refractive aberration manipulation (LuxSmart), continuous transition diffractive optics (Rayner EMV), and spherical aberration modulation (Eycryl SERT). Each represents a different approach to creating an elongated focal point rather than discrete foci, theoretically providing enhanced intermediate performance while minimizing visual disturbances associated with multifocal designs. Study Design and Methodology Design Framework: This prospective, single-center, comparative clinical trial employs a patient-preference methodology rather than traditional randomization. This approach reflects real-world clinical practice where IOL selection involves shared decision-making between surgeon and patient based on individual visual needs, lifestyle requirements, and risk tolerance. Patient-Preference Rationale: The patient-preference design was selected to: (1) respect patient autonomy in premium IOL selection, (2) minimize ethical concerns associated with randomizing patients to potentially suboptimal treatments based on individual needs, and (3) generate clinically relevant real-world evidence regarding patient-chosen outcomes and satisfaction levels. Surgical Standardization: All procedures are performed by a single experienced surgeon using standardized phacoemulsification technique with identical surgical parameters: 2.5mm superior corneal incision, 5.5mm continuous curvilinear capsulorhexis, horizontal chop phacoemulsification, and bilateral same-model IOL implantation. Target refraction aims for emmetropia with slight myopic bias. Primary Assessment Domains Intermediate Visual Performance Distance-Specific Testing: The protocol emphasizes comprehensive intermediate visual assessment at two critical distances: 80cm and 60cm. These distances represent distinct functional zones - 80cm corresponds to automobile dashboard and extended arm's length tasks, while 60cm represents standard computer monitor and kitchen counter distances. Measurement Methodology: Both uncorrected intermediate visual acuity (UIVA) and distance-corrected intermediate visual acuity (DCIVA) are assessed monocularly and binocularly under standardized photopic conditions (85 cd/m²) using high-contrast charts. Multiple chart sets prevent memorization effects across repeated assessments. Clinical Significance Threshold: The study is powered to detect clinically meaningful differences of 0.1 logMAR in DCIVA, representing approximately one line of visual acuity improvement that translates to functional benefits for intermediate tasks. Defocus Curve Analysis Defocus curve: Binocular defocus curve testing employs defocus lenses from +1.50D to -2.50D in randomized order, corresponding to simulated viewing distances from infinity to 40cm. Depth of Focus Quantification: Two threshold levels (0.1 and 0.2 logMAR) define depth of focus as the dioptric range from 0.00D defocus to the largest negative defocus value maintaining threshold visual acuity. This methodology provides standardized assessment of extended focal range capabilities across IOL technologies. Functional Vision Range: The defocus curve demonstrates each IOL's usable vision range, identifying optimal performance zones and transition points where visual quality degrades. Contrast Sensitivity Assessment Multi-Condition Testing: Contrast sensitivity evaluation employs the Functional Vision Analyzer across five spatial frequencies (1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree) under three standardized lighting conditions: photopic (85 cd/m²), mesopic (3.0 cd/m²), and mesopic-with-glare (3.0 cd/m² background with 28 lux glare source). Real-World Simulation: The three testing conditions simulate actual visual environments: photopic represents daylight conditions, mesopic simulates twilight or indoor lighting, and mesopic-with-glare replicates challenging scenarios such as night driving with oncoming headlights. Patient-Reported Outcomes Validated Questionnaires: Two established instruments assess subjective visual experience: Visual Function Index-14 (VF-14): Evaluates functional visual performance across 14 daily activities including reading, driving, recognizing faces, and performing fine tasks. Each item scores 0-4 with responses weighted by individual importance, generating a 0-100 scale where higher scores indicate better visual function. McAlinden's Quality of Vision: Assesses patient-reported visual symptoms including glare, halos, starbursts, hazy vision, distortion, and focusing difficulties. Three Rasch-tested scales measure symptom frequency, severity, and bothersome impact on daily activities. Spectacle Independence Assessment: Comprehensive evaluation of spectacle dependence across distance, intermediate, and near tasks, with particular emphasis on complete spectacle independence rates and task-specific visual function. Statistical Methodology Sample Size Calculation: Power analysis targets detection of 0.1 logMAR differences in DCIVA with 90% power and α=0.05, accounting for 10% attrition, requiring 200 eyes (25 patients per group). Analysis Approach: Generalized linear modeling with inverse Gaussian regression and identity link accommodates logMAR data characteristics. Multiple Comparison Control: Sequential Bonferroni correction controls Type I error while maintaining statistical power, with the monofocal CT ASPHINA 409M serving as the reference comparator for all pairwise analyses. Clinical Assessment Timeline Preoperative Evaluation: Comprehensive baseline assessment includes biometry, corneal tomography, specular microscopy, optical coherence tomography, and complete ophthalmologic examination to ensure optimal surgical candidacy and establish baseline parameters. Postoperative Follow-up: Standardized assessments at 1 day, 1 week, 1 month, and 3 months postoperatively. Primary endpoints are assessed at 1 and 3 months to capture visual stabilization and adaptation effects. Safety Monitoring: Continuous assessment of IOL stability, posterior capsule opacification development, and complication rates throughout the follow-up period. Innovation and Clinical Impact This protocol represents the first comprehensive head-to-head comparison of four contemporary IOL technologies using standardized methodology and validated outcome measures. The emphasis on intermediate visual performance, quantitative depth of focus analysis, multi-condition contrast sensitivity assessment, and patient-reported outcomes provides clinically relevant data for evidence-based IOL selection and patient counseling in modern cataract surgery practice.

The standard of care for high-risk breast cancer consists of neoadjuvant chemotherapy and surgery followed by postoperative whole breast/chest wall irradiation+/- an additional boost (= irradiation restricted to the tumour bed in the case of breast-conserving therapy). In case of lymph node involvement in most patients require additional radiation of the regional lymph nodes. Adjuvant radiotherapy significantly reduces ipsilateral breast cancer recurrences, breast cancer specific mortality, and overall mortality. The optimal time of radiotherapy in patients, who are candidates for neoadjuvant chemotherapy (NACT) has never been addressed in a randomised controlled trial. The Study Chairman of the NEORAD trial is Prof. Dr. med. Christiane Matuschek. The deputies of the Study Chairman are Prof. Dr. med. Wilfried Budach and Prof. Dr. med. Tanja Fehm.

This registry is performed for the long-term assessment of outcome, performance and residual safety aspects of the BIOMONITOR III and possible successors in a real-life clinical set-up. In addition, this registry is set up in a way that it may also be used as a platform for submodules to investigate additional scientific and regulatory aspects while minimizing the additional effort for the investigational sites and patients.

Patients who have survived a myocardial infarction (MI) are at increased risk for sudden cardiac death (SCD) caused by ventricular tachycardia and ventricular fibrillation. A severely reduced left ventricular ejection fraction (LVEF) as a rough overall measure of impaired heart function after MI was shown to indicate a higher risk for SCD. Based on this observation, two landmark randomised trials, MADIT II and SCD-HeFT, were conducted between end of the 1990s and early 2000s. These trials compared the survival of patients with severely reduced LVEF who received an implantable cardioverter-defibrillator with the survival of patients being on medical therapy alone. They reported a significantly better survival of patients in the defibrillator arm and led to international guideline recommendations for routine implantation of defibrillators in survivors of MI with severely impaired LVEF as a means for primary prevention of SCD. Since then, the management of these patients has changed dramatically with the advent of a series of novel drug classes that reduce not only mortality but specifically SCD leading to a substantial decrease of the sudden death rates as well as of the rates of appropriate defibrillator therapies implanted for primary prevention of SCD. At the same time, the complication rates associated with the defibrilllator therapy remain significant without obvious decrease. Thus, the risk-benefit of routine defibrillator implantation for primary prevention of SCD in patients with severely reduced LVEF has substantially changed since the conduction of the landmark trials that established this therapy. Due to the inherent risks and considerable costs of the defibrillator, a novel randomised adequately powered assessment of the potential benefit or harm of the defibrillator in survivors of MI with reduced LVEF under contemporary optimal medical treatment (OMT) appears imperative. OBJECTIVE: To demonstrate that in post-MI patients with symptomatic heart failure who receive OMT for this condition, and with reduced LVEF ≤ 35%, OMT without ICD implantation (index group) is not inferior to OMT with ICD implantation (control group) with respect to all-cause mortality.

This is a Prospective, non-interventional (NIS) observational study in patients (≥6 years) with atopic dermatitis (AD) receiving dupilumab for the prospective evaluation of signs and symptoms, quality of life and disease control. The aim of this NIS is the characterization of the AD patient population in Germany, receiving dupilumab under everyday conditions in terms of their medical history, socio-demographic and disease-related characteristics, associated atopic comorbidities and type 2 inflammation diseases, concomitant therapy as well as previous systemic and ongoing AD treatments. In addition to the therapeutic response rate at Month 6, the long-term efficacy of dupilumab at Month 12 and Month 24 will be assessed by additional outcomes by measuring disease control in AD patients using questionnaires such as Atopic Dermatitis Control Tool (ADCT) and Recap of Atopic Eczema (RECAP). In addition, this NIS aims to assess the dosing pattern of dupilumab for AD, including variations in dosing regimen, reason for dupilumab treatment initiation or discontinuation, or change in therapy and concomitant therapies and duration of treatment. In addition, the effect of dupilumab in adult and pediatric AD patients with associated atopic comorbidities or type-2 inflammation diseases are observed, which corresponds to the clinical care situation. Finally, this NIS aims to collect long-term safety data in adult, adolescent and pediatric AD patients treated with dupilumab. Individual observation period is 2 years or until dupilumab is discontinued. Visits will be scheduled according to standard of care.