Clinical trials

The Endoprosthesis Registry Heidelberg (EPR-HD) is a clinical registry designed to systematically collect and analyze data from patients undergoing primary implantation or revision surgery of artificial hip and knee joints. The main objective of the registry is to evaluate long-term outcomes, complication rates, implant survival, and functional results associated with joint replacement procedures in patients with various hip and knee joint pathologies. By gathering comprehensive clinical data, EPR-HD aims to improve the understanding of patient outcomes after endoprosthetic procedures, identify potential factors influencing implant success, and support evidence-based improvements in surgical techniques and patient care. The registry includes adult patients treated at Heidelberg University Hospital, with data collected at multiple time points during routine clinical follow-up. This registry will contribute to the optimization of joint replacement strategies and promote high-quality patient care.

This study is a mixed-methods, single-arm cross-sectional study comprising 1) a qualitative, exploratory, critical-constructivist content analysis examining the significance of gender in relationship experiences and self-perception among individuals with borderline personality disorder and various gender identities, and 2) a pilot study on the use of the Single-Category Implicit Association Test (SC-IATs, adapted from von Hippel et al., 2018) as preparation for a larger-scale experimental psychological study using the SC-IAT to assess implicit gender- and BPD-related thought processes in people with borderline personality disorder and various gender identities. 15 individuals with BPD and different gender identities will be assessed. The research questions are: 1. What gender-related relationship- and self-experiences can be identified in people with BPD? How do experiences relate to observer-coded and self-reported mentalization ability, as well as self-reported symptoms, experiences of stigmatization, and quality of life? 2. Is there preliminary evidence that Single-Category Implicit Association Tests (SC-IATs) are suitable and reliable instruments for measuring implicit gender- and BPD-related thought processes in people with BPD?

Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter. The aim of the GRIPS study is to prospectively test this clinical benefit in a randomized, open-label Phase III study. Patients are treated in the study using either modern photon radiation techniques (standard arm) or proton beams (experimental arm). The primary endpoint is the cumulative toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition.

Optimal anesthetic mode is not established for patients with vertebrobasilar stroke undergoing endovascular treatment. We want to investigate whether a procedural sedation mode approach is feasible compared to general anesthesia

The aim is to record and document a mediastinal PT and the corresponding follow-up data (effectiveness and side effects). General recommendations for planning and feasibility are made within the framework of this study.

The goal of this clinical trial is to investigate the impact of repetitive acute Cyclosporine A (CsA) bolus therapy in patients suffering from TTS with an elevated risk of impaired outcome. The main question it aims to answer is whether CsA reduces myocardial injury (primary outcome). Participants will receive CsA or placebo at baseline and every 12h in the first 24h after study inclusion. Researchers will compare CsA and the placebo group to see if a) myocardial injury is reduced, and b) ejection fraction is improved compared to baseline, as well as several other secondary endpoints over a one year follow-up.

This randomized prospective open-label phase 2 trial testes the safety and feasibility of a hypofractionated accelerated neoadjuvant proton or carbon ion radiotherapy based on the rate of wound healing disorders from beginning of radiotherapy to maximum 120 days after the planned tumor resection or discontinuation of treatment due to any reason. The treatment is of shorter duration (2-3 weeks vs. 5 weeks standard treatment), which should please most patients and thus enhance quality of life. The treatment regimen furthermore promises a reduced rate of late side effects and significant optimization of the current treatment standards. A phase II trial is mandatory not only for obtaining the safety and feasibility data, but also in order to prepare a concurrent phase III trial. Due to the low incidence of soft tissue sarcoma, only a well prepared multicenter study has a chance to be successfully completed based on previous experiences in trials for seldom tumor entities.

ARTIFICE is a prospective, multicenter, randomized, controlled, exploratory non-inferiority trial evaluating whether an ambulatory stroke unit model (aSU) is non-inferior to conventional inpatient stroke unit care (SU) in patients aged 60 years or older with acute ischemic stroke, transient ischemic attack (TIA), or retinal ischemia and non-disabling neurological deficits. Eligible patients are randomized 1:1 to same-day comprehensive ambulatory multiprofessional stroke evaluation (aSU) or guideline-based inpatient stroke unit treatment (SU). The primary endpoint is favorable functional outcome at 90 days, defined as modified Rankin Scale (mRS) 0-2 or return to pre-stroke mRS. Endpoint assessment at 90 days is performed by blinded assessors (PROBE design). Secondary outcomes include early neurological deterioration, recurrent stroke, delirium, mortality, health-related quality of life, healthcare utilization, and cost-effectiveness. A mixed-methods process evaluation examines feasibility, acceptability, and implementation aspects of the ambulatory care model.

After multimodal therapy of head-and-neck tumors, patients often develop local recurrence, locally progressive disease or second primary tumors. In this highly pre-treated patient cohort, therapeutic options are limited. Patients that are not candidates for salvage surgery may benefit from re-irradiation. Despite recent technical advances, re-irradiation is associated with severe side effects. Carbon ion Re-Radiotherapy (reCIRT) has shown encouraging results in retrospective analyses with moderate toxicity. In the current Phase-II CARE-trial, reCIRT and conventional photon re-irradiation in patients with recurrent or progressive locally advanced head-and-neck cancer will be assessed regarding toxicity/ safety, local progression-free survival, overall survival and quality-of-life.

Breast cancer is the most common malignancy in women. Breast-conserving surgery (BCS) with adjuvant whole-breast irradiation (WBI) is currently the standard of care in the oncological treatment of primary breast cancer and offers an equivalent alternative to mastectomy. The primary aim of adjuvant radiotherapy (RT) is to improve local control and thus improve overall survival and breast cancer-specific mortality. However, nodal-negative women have a 10-year risk for local recurrences after RT in up to 15.6%. The management of ipsilateral breast cancer recurrence depends on the extent of tumor disease and staging results at the time of recurrence and mastectomy is currently the standard of care for previously irradiated patients. The application of particle therapy using proton beam therapy (PBT) represents an innovative radiotherapeutic technique for breast cancer patients. This trial will be conducted as a prospective single-arm phase II study in 20 patients with histologically proven invasive breast cancer recurrences with negative margins after repeat BCS and with an indication for local re-irradiation. Required time interval will be 1 year after previous RT to the ipsilateral breast. Patients will receive partial breast re-RT with proton beam therapy in 15 once daily fractions up to a total dose of 40.05 GyRBE. The primary endpoint is defined as the cumulative overall occurrence of acute / subacute skin toxicity grade ≥3 within 6 months after the start of re-RT.

The study examines the diagnostic precision of endosonography, mpMRI and PET/CT in defining tumor boundaries and tumor spread before and after neoadjuvant therapy and definitive surgery.

While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring.

Patients suffering from malignancies in advanced stages often develop brain metastases, which limit both the life span and the quality of life. Therapy options for multiple brain metastases may vary and range from stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), chemotherapy, immunotherapy to palliative best supportive care. Especially the efficacy and toxicity of SRS compared to WBRT in patients with extensive brain metastases (\>4) is not yet clear but of incremental relevance in this seriously ill cohort with a limited life span. These health-impaired patients might especially profit from a less toxic treatment that is also time sparing with 1 or few sessions in SRS versus 10 sessions in WBRT. On the other hand, no compromises in efficacy want to be done.

Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastases. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. MR-guided radiotherapy (MRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT (MRgSBRT) compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach (ITV-SBRT).

The study is a randomized, open, prospective phase II study. The aim of the study is to evaluate the safety and feasibility of a hypofractionated, accelerated radiation approach based on the incidence of grade 3-5 NCI Common Terminology Criteria for Adverse Events (NCI-CTC-AE ) toxicity and / or termination of the planned therapy for any reason with neoadjuvant radiation with active beam guidance of the retroperitoneal Sarcomas using protons or carbon ions before a subsequent tumor resection.

As the most common male carcinoma, prostate cancer is a major tumor entity in oncology. In addition to definitive radiotherapy, surgical procedure is considered to be an oncologically equivalent therapeutic alternative for non-metastatic malignancies in the primary setting. However, a subsequent radiotherapy of the prostate bed is often necessary, which takes place as an "adjuvant" treatment immediately after surgery or in the course of a repeated increase in PSA and usually extends over several weeks. For the primary situation (without previous surgery), several randomized phase III clinical trials have shown that it is possible to shorten radiotherapy by increasing the single dose (called hypofractionation). In the context of two prospective Phase II studies, which were carried out in Heidelberg, it has since been shown that hypofractionation with both photons and protons is safe and feasible even in the postoperative situation. The current, prospective and randomized PAROS study is now intended to demonstrate a multicentric phase III study as an improvement in the quality of life caused by rectum toxicity (primary endpoint) by the use of protons. The oncological non-inferiority of hypofractionated radiotherapy after surgery is a secondary endpoint.

Periodontitis is a prevalent chronic inflammatory disease driven by a dysbiotic oral biofilm and a dysregulated host immune response. Standard non-surgical periodontal therapy (NSPT) is primarily mechanical and, in selected cases, may be accompanied by antiseptics or systemic antibiotics. Targeted modulation of the oral microbiome ("microbiome engineering") is currently not part of routine periodontal care due to limited high-quality evidence. PROPARO is a single-center, randomized, controlled pilot study designed to assess whether adjunctive oral supplementation with a probiotic containing Limosilactobacillus reuteri (commercial dietary supplement lozenge) alone or combined with vitamin B12 (commercial dietary supplement drops) is associated with changes in supragingival and subgingival oral microbiome composition during guideline-concordant NSPT compared with standard care alone. Participants with Stage III or IV periodontitis will be randomized 1:1:1 to: (1) NSPT/SPT without supplementation (control), (2) NSPT/SPT plus probiotic lozenges for 3 months, or (3) NSPT/SPT plus probiotic lozenges and vitamin B12 drops for 3 months. The primary outcome is change in oral microbiome composition and structure (supragingival and subgingival), assessed using 16S rDNA-based profiling and metagenomic sequencing approaches. Secondary outcomes include clinical periodontal parameters (e.g., probing depth, clinical attachment level, bleeding on probing), oral hygiene/gingival indices, dental status, and participant-level ecological covariates (diet quality, perceived stress, physical activity). Sampling and assessments are aligned with routine care time points from baseline through supportive periodontal therapy follow-up (up to 12 months). This pilot trial aims to generate feasibility and effect-size estimates to inform future confirmatory studies and potential translation into guideline-based periodontal care.

Physical exercise is an important supportive therapy for cancer patients, as it improves quality of life in general and might mitigate the side effects of drug treatment. For patients with multiple myeloma in particular, significantly less evidence on the effectiveness of exercise therapy is available due to the fact that this disease is associated with severe bone degradation which might affect bone stability. Advances in oncologic drug treatment have improved overall survival in multiple myeloma significantly. Therefore, there is an increased interest for recommendations on physical activity in this patient group. Due to uncertainties regarding safety and feasibility of exercise therapy in multiple myeloma, both patients and therapists often remain hesitant. Therefore, an orthopaedic outpatient clinic has been established at the Myeloma Center of Heidelberg University Hospital. Here, patients receive consultation on bone stability and individualized physical exercise plans. Based on the expertise gained at the orthopaedic outpatient clinic, the aim of this study is to establish and evaluate structural measures for improved rehabilitation in multiple myeloma and to integrate them into routine clinical care.

Oligodendrogliomas in the novel edition of the Central Nervous System (CNS) World Health Organization (WHO) classification are now molecularly defined by isocitrate dehydrogenase (IDH)1 or IDH2 mutations and 1p/19q co-deletion. The prognosis of these molecularly defined tumors is to be determined in new series since survival data from older histology-based studies and population-based registries are confounded by the inclusion of 20-70% not molecularly matching subsets. Also, the optimal treatment is a matter of ongoing investigations. An extensive, but safe surgery is associated with improved outcome as is the addition of chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) to the partial brain radiotherapy (RT). However, the exact timing of postsurgical therapy especially for tumors of the WHO grade 2 and acknowledging some variability in grading as well as the choice of chemotherapy, temozolomide instead of PCV (CODEL: NCT00887146 randomizing CNS WHO grade 2 and 3 oligodendrogliomas to chemoradiation(CHRT)therapy with PCV or with temozolomide) or the need for primary radiotherapy RT are subjects of clinical studies (POLCA: NCT02444000 randomizing patients with newly diagnosed CNS WHO grade 3 oligodendrogliomas to standard CHRT with PCV or PCV alone). Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumor located in the brain optimizing care is the major challenge. NOA-18/IMPROVE CODEL aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG), thereby delaying radiotherapy (RT) and adding the chemoradiotherapy (CHRT) concept at progression after initial radiation-free chemotherapy, allowing for an effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life (QOL) deterioration regardless whether tumor progression or toxicity is the main cause.

Intracerebral hemorrhage (ICH) is a debilitating and fatal disease, especially when the hemorrhage is also entering the cerebral ventricles leading to acute hydrocephalus. In these cases, patients need a drainage through external ventricular drains (EVD). In the longer term, patients often need a permanent ventriculoperitoneal (VP) shunt to avoid hydrocephalus. Here we hypothesize that the early insertion of a lumbar drainage in addition to the EVD could lead to better functional outcome and avoidance of VP shunting by drainage of the blood which promotes inflammatory and adverse effects in the subarachnoid space. For that we propose a multi-center randomized clinical trial to investigate the hypothesis.

The goal of this clinical trial is to learn if a longer period of lying on the back after corneal transplant surgery (Descemet Membrane Endothelial Keratoplasty, DMEK) helps the transplant stick better in the eye. It will also learn about side effects, such as back pain. The main questions it aims to answer are: * Does lying on the back for 5 days reduce the size of transplant detachment compared to lying on the back for only 1 day? * Do participants who lie on their back longer need fewer additional procedures (rebubbling)? * What symptoms or problems do participants experience with short vs. long back positioning? Researchers will compare two groups: * 1 day of back positioning * 5 days of back positioning Participants will: * Be randomly assigned to one of the two positioning groups * Wear a movement sensor that records head position * Have their eyes checked regularly with vision tests and imaging (AS-OCT) * Answer questions about their vision and comfort * Keep a diary of any positioning-related complaints, such as back pain

Approximately one third of the population over the age of 65 falls at least once a year. The risk of falling is in increased in older patients with tumor diseases. In addition to high treatment and care costs for the healthcare system, falls often lead to a decrease of quality of life, a reduction in physical performance and a loss of independence. Despite the high risk, falls in cancer patients have not yet been scientifically investigated in detail. For patients with multiple myeloma in particular, very little data is available on the prevalence, risk factors and effects of falls. In this study, a fall risk assessment is carried out in patients with multiple myeloma. Furthermore, a patient-specific training intervention for fall prevention will be implemented. The aim of the study is to identify possible fall risk factors in multiple myeloma patients and to establish a structured exercise intervention that minimizes the risk of falls and injuries.

Kidney transplantation remains the only definitive treatment for end-stage renal disease, yet the increasing use of extended criteria donor (ECD) kidneys heightens the risk of ischemia-reperfusion injury, particularly under static cold storage (SCS). Continuous hypothermic machine perfusion (HMP) has been introduced to improve preservation quality, but robust clinical evidence regarding its predictive value for post-transplant outcomes in ECD kidneys after donation after brain death (DBD) is limited. The PRE-MAP Kidney Study is a prospective, non-interventional, multicenter observational study conducted across all German transplant centers. The study systematically collects technical machine perfusion parameters (flow, resistance, perfusion duration) and correlates these with clinical outcomes following kidney transplantation. The primary endpoint is 12-month kidney function (eGFR). Secondary endpoints include surgical complications, length of stay, and transplant-specific events (acute rejection, primary non-function, delayed graft function). This national cohort aims to determine the prognostic significance of HMP parameters in marginal donor kidneys and to generate evidence supporting future recommendations for organ preservation and allocation practices.

The main objective of this study is to investigate the utility of functional MRI to differentiate, characterize, and monitor subgroups of ILD. This can be broken down into three specific objectives: Determine if ILD features observed on high-resolution computed tomography (HRCT), such as ground glass opacities (GGO), are functionally different. Analyse MRI metrics within each subgroup to determine whether these metrics distinguish different ILDs. Assess MRI metrics longitudinally to see if these parameters change with disease progression, stability, or reversibility.

The goal of this clinical trial is to investigate if Mentalization-based therapy (MBT) is superior to enhanced usual care (treatment-as-usual-plus (TAU-plus)) for adolescents with disruptive behavior or dissocial disorders. MBT is an intervention that aims to improve mentalizing. Mentalizing is the ability to reflect on mental states in oneself and others that motivate behavior. TAU-plus consists of psychiatric care for the adolescent, along with additional emotion-focused skills training for the parents. Participants will be randomized in one of two groups using one study center.