Clinical trials

The main objective of the genetic newborn screening part of the Screen4Care-project is to shorten the path to rare disease diagnosis and to facilitate early intervention. Therefore, genetic newborn screening for currently treatable rare diseases (TREAT-panel approach) will be offered to families expecting a baby. Whole genome sequencing (WGS) will be offered as additional diagnostic approach to newborns participating in Screen4Care TREAT-panel approach, if they develop symptoms suggestive of a genetic disease. To evaluate to what extend genetic newborn screening has an impact on participating infants and their families, a follow-up with standardised questionnaires will be performed for all participating families.

The aim of the study is to improve the accuracy of diagnosis for children and adolescents with MDS by a standardized review of morphology and standardized cytogenetic and molecular analysis. The primary objectives of the study are: * To evaluate the frequency of the different subtypes of MDS in childhood and adolescence by a standardized diagnostic approach * To evaluate the frequency of cytogenetic and molecular abnormalities: Specifically using array-CGH to evaluate the frequency of subtle chromosomal imbalances, i.e. gains and losses of defined chromosomal regions, and amplifications. Specifically using mFISH to identify unknown chromosomal aberrations, particularly subtle translocations involving new candidate genes, and to better define chromosomal breakpoints. The secondary objectives of the study are: * To assess survival for children and adolescents with MDS and JMML * To evaluate relapse rate, morbidity and mortality in children with MDS and JMML treated by HSCT

The aim of this clinical trial is to compare the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) implantation with standard treatment (diuretic medications, and if necessary, paracenteses) in patients with liver cirrhosis and development of ascites as the first decompensating event. By creating a shunt between the liver vein and the portal vein, blood is diverted from the portal vein directly into the hepatic vein, which results in a reduction of pressure in the portal vein so that development of ascites is reduced.

Small bowel capsule endoscopy is the main diagnostic standard for small bowel bleeding. This study investigates the detection rate of small bowel bleeding in capsule endoscopy and further endoscopic treatment in a prospective and retrospective cohort.

Patients with clinically significant portal hypertension allocated to implantation of a transjugular intrahepatic portosystemic shunt (TIPS) at the Department of Medicine II of the University Medical Center Freiburg, Germany will be offered to participate in this prospective observational trial. Clinical and laboratory as well as outcome parameters will be assessed before and within the first 12 months after TIPS implantation following a regular follow-up schedule with clinical visits at the University Medical Center Freiburg. During follow-up visits, serum/plasma samples and peripheral blood mononuclear cells (PBMC) are collected and stored in a associated biobank.

Bedside colonoscopy 24-36 hours after successful CPR

Background: Bloodstream infections (BSIs) and sepsis continue to pose significant public health challenges, contributing to high morbidity and mortality worldwide. According to the Global Burden of Diseases Study, BSIs and sepsis are associated with approximately 20% of global deaths. However, the clinical characteristics of BSIs have evolved over recent years, showing significant variability across different countries and continents. The diversity in management standards across regions further complicates the generalization and transferability of research findings. Despite the critical need for comprehensive data, BSI research in Europe remains fragmented, often limited to national-level studies. Project Aim: The EPIC-BSI project aims to address these challenges by establishing a multinational, collaborative bloodstream infection cohort across Europe and globally. The primary objectives are to: * Integrate national BSI research into a cohesive multinational cohort that enable large-scale comparative research by standardizing BSI incidence data, diagnostic and therapeutic approaches, and patient outcomes across European countries and beyond. * Monitor shifts in BSI characteristics, including the emergence of multi-drug resistant organisms, and changes in risk groups, diagnostics, and therapies. * Create a foundation for future studies and collaborations, such as integrating BSI data with international antibiotic usage, population data, health policy data, or by biobanking blood-borne pathogens for sequencing. The study is divided into three arms focusing on BSI epidemiology (EPIC-BSI registry), diagnostics (EPIC-BSI Diagnostic Study) and management (EPIC-BSI Management study). The EPIC-BSI Management study is partitioned in different levels of data contribution to reduce barriers for centres and enable broad participation. Specific Objectives and Endpoints: EPIC-BSI Registry: * Primary aim/endpoint: Establish an international prospective BSI cohort with anonymized inclusion of all BSI cases from participating centres allowing estimation of BSI incidence by pathogen in the participating centres. * Secondary aims/endpoints: * Analyse the incidence of BSIs across different settings and countries. * Monitor changes in patient demographics (age, gender) and acquisition modes. * Track shifts in antimicrobial resistance patterns. * Review effects of infection control practices on MDRO-BSI frequency EPIC-BSI Diagnostic Study: * Primary aim/endpoint: Biannual evaluation of diagnostic procedures and standards regarding BSI at participating centres * Secondary aims/endpoints: * Assess the availability and use of (new) clinical and microbiological diagnostics. * Identify gaps in diagnostic practices and time lags between scientific evidence, guideline publication and clinical implementation of new diagnostic utilities. EPIC-BSI Management Study: * Primary aim/endpoint: Analyse clinical data from BSI cases to evaluate management practices regarding the effect on in-hospital mortality and outcome on day 90 after onset incl. patient-reported outcomes (Desirability-of-outcome-ranking (DOOR) or health-related quality of life metrics) * Secondary aims/endpoints: * Identify differences in clinical management across countries and hospital types. * Analyse the impact of antimicrobial resistance patterns on clinical outcomes. * Evaluate the effectiveness of different established therapeutic regimens.

The number of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing; however, the evidence regarding the ideal treatment for this often vulnerable and frail patient cohort is limited. Although the benefit of concomitant chemotherapy has been reported to decrease in elderly HNSCC patients based on the MACH-NC meta-analysis, it remains unknown whether state-of-the art radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), modern supportive treatments and alternative chemotherapy fractionation (e.g., cisplatin weekly) may have altered this observation. The objective of this retrospective multinational multicenter study is to determine the oncological outcomes of elderly patients (≥65 years) with locally advanced HNSCCs undergoing definitive (chemo-)radiation and to investigate the influence of concomitant chemotherapy on overall survival and progression-free survival after adjusting for potential confounder variables such as age, performance status and comorbidity burden.

Most patients being diagnosed with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) are 60 years or older. Elderly patients with PCNSL have a poor prognosis and there is a great medical need to improve outcome for this vulnerable population. In Germany and many international centres, there are currently two widely used strategies to treat elderly PCNSL patients who are eligible for high-dose methotrexate (HD-MTX) treatment, which have not yet been compared head-to-head. The R-MP regimen has been established by the Cooperative PCNSL Study Group as a "conventional" immunochemotherapy standard treatment for elderly patients with newly diagnosed disease and consists of Rituximab, HD-MTX and Procarbazine followed by maintenance therapy with Procarbazine. In contrast, another recently established protocol also includes HD-MTX-based induction therapy, but followed by consolidating high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT). This is an overall more intensive, but substantially shorter treatment approach, feasible for elderly patients being considered eligible for a more intensive treatment. The PRIMA-CNS trial aims to compare these two treatment approaches with respect to survival, response rates and toxicity.

Helicobacter pylori affects the gut microbiome in ways that are only partially understood. In which patients H. pylori causes severe disease and in whom it merely colonizes, possibly even with beneficial effects, is not understood. The investigators are pursuing the hypothesis that changes in the gut microbiome that can be easily measured in stool have such predictive value.

Spinal CSF leaks are considered as rare disease. They cause a variety of symptoms, mainly culminating in a chronic headache syndrome. Crucially, yet often disregarded, the disease holds the potential for cure. The multitude of symptoms, and their inconsistency over time are just two of many challenges preventing timely diagnosis and treatment in many patients. Spinal CSF leaks can occur after intentional or accidental dural puncture (post-dural puncture headache - PDPH) or spontaneously (spontaneous intracranial hypotension - SIH). Awareness is steadily increasing with simultaneous increase of recognized patients. Yet, research and diagnostic is mainly provided by few specialized centers, as e.g. Freiburg. Thus, many observations point towards a large non-diagnosed and non-recognized number of patients, most likely being misdiagnosed and mistreated. Objective: The aim of the registry is to collect structured information on the frequency, cause, symptoms, diagnostic procedures, treatment options and long-term outcome. With the help of the registry, we would like to contribute to a better understanding and treatment of the diseases. Methods: Prospective, longitudinal registry on patients with suspected SIH or PDPH, including data on demographics, clinical presentation, diagnostic findings, treatment, at treatment outcome.

This study aims to gather insights into the perceptions of legal representatives regarding the recruitment process for clinical trials in the intensive care setting when the patients cannot decide for themselves. With this information, effective strategies will be developed to increase involvement and the feeling of ownership of LARs of (potential) participants in clinical trials and thus enhance and facilitate patient recruitment for clinical trials. The single-arm study design does not include a choice of comparator, as the focus of this trial is to explore the perceptions of the participants at first hand without comparing different cohorts or strategies.

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time and by (ii) enabling a safe delivery of high RT doses. Several studies proposed a dose-response relationship for patients with primary prostate cancer (PCa) and especially in patients with high-risk features a dose escalation should lead to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography (PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time. The HypoFocal-SBRT study combines ultra-hypofractionated RT / stereotactic body RT (reduction of treatment time) with a focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts. This novel concept will be compared with moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide. We suspect an increase in relapse-free survival (RFS) and we will also assess quality of life in order to detect potential changes.

In this first-in-human clinical trial a novel generator (INTELLAPULSE), designed and built by Stockert, which supports highly flexible PFA protocols as well as RF interventions will be used. For 12 months and follow-up for 12 months, after a 3-months blanking period 50 consecutive paroxysmal AF patients, eligible for catheter ablation, will be enrolled.

Coronary heart disease and its acute complication, myocardial infarction (MI), represent the leading causes of death in Europe and the United States. Although novel treatment strategies have helped to improve survival in patients with MI, a large proportion of patients develops heart failure and is at risk of life-threatening arrhythmias. Complications arising after MI constitute a severe burden not only for the patients themselves, but also for health care systems worldwide. The likelihood of these complications depends on the area of myocardial tissue lost and the process of myocardial repair and scar tissue formation after MI ('remodeling') which are modified by the local and systemic immune response after MI. The immune response is critical after myocardial infarction. In particular, sustained overactive and prolonged inflammatory reactions lead to accentuated myocardial damage and dysfunction. Important mediators of the inflammatory reaction after MI are monocytes, T-cells, B-cells and hematopoietic stem and progenitor cells. Following MI, myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. T- and B-cells in particular act in response to specific antigens. Most of the data regarding the inflammatory response after MI, however, are derived from animal models. The immunological phenotypes after MI and their association with clinical outcome in humans are insufficiently characterized. Aims: The aim of this project is to provide establish clinically and immunologically well-characterized cohort of patients after MI This will aid in identifying novel prognostic cellular and humoral biomarkers that may be used to identify patients at a high inflammatory and immune risk and to guide clinical management. Furthermore, these mediators, in the future, may be targeted by novel antigen-specific immunomodulatory approaches. Patients with myocardial infarction (STEMI and NSTEMI) will be recruited after PCI within 24h and receive a structured follow-up. Clinical read-outs include a detailed and standardized patient history, clinical examination, standard blood work, coronary angiography, ECG, echocardiography and for subgroups, MRI. Patients will present for study visits at 6 weeks, 3 months and 12 months after the initial event. Blood will be sampled at the inclusion and during follow-up visits. Peripheral blood mononuclear cells and plasma will be stored at the Cardiovascular BioBank (CVBB) and FREEZE, both institutions at the University Hospital in Freiburg. Major adverse cardiac events (myocardial infarction, stroke, hospitalization for heart failure, cardiovascular death) will be recorded using telephone interviews and standardized queries to the local authorities. Several laboratory read-outs are planned including flow cytometry, mass cytometry, single cell RNA sequencing, T cell and B cell receptor sequencing and bulk-RNA-sequencing. In an initial approach we aim to recruit 400 patients with MI, of which we expect ≈40 to develop ischemic cardiomyopathy. Differences in immunological profiles between patients that develop MI and a propensity-matched control group will then be analyzed and correlated with clinical outcome data.

A prospective registry collecting pseudonymized clinical and treatment data from all patients treated with extracorporeal organ support (i.e., VV ECMO, VA ECMO, ECPR, Impella, IABP, and others) on the wards of the Department of Interdisciplinary Medical Intensive Care at the Freiburg University Medical Center.