Großhansdorf, Germany

The Next Step Towards the Elimination of Iodine Deficiency and Preventable Iodine-related Disorders in Europe

Detailed Description: BACKGROUND: Iodine deficiency (ID) is a leading risk factor for thyroid disorders and developmental impairments in offspring. It is recognized as one of the most preventable causes of mental impairment in children. The EUthyroid2 project aims to contribute to the prevention of ID and its associated symptoms and disease burden in adolescents across Europe and beyond. AIM: This project seeks to develop and implement an educational intervention in various educational settings, effectively raising awareness of the risks associated with iodine deficiency. METHODS: The intervention will be conducted in each participating country, with three clusters (secondary schools, high schools, and vocational schools) per country. The goal is to achieve a final sample of 4500 study participants in all countries combined, involving one baseline measurement and two follow-up assessments (2-4 weeks and 6-8 months post-intervention). Data will be collected at all measurement points, with variations in implementation accounted for due to differences between countries. To ensure the intervention's functionality and effectiveness, the project will consider recommendations for developing complex interventions, appropriate theoretical frameworks, and conduct a context analysis. Outcome measures will include a newly developed iodine awareness questionnaire (primary outcome) and an iodine-specific food frequency questionnaire. Additionally, socio-demographic characteristics will be measured. Descriptive analyses will be performed on all variables, with subgroup and country-specific analyses computed. A process evaluation will assess the implementation process using a convergent parallel mixed methods design, inviting teachers and students to participate in an online questionnaire. Semi-structured interviews will further enrich this evaluation. CONCLUSION/OUTLOOK: The results of the EUthyroid2 project may assist health authorities across participating countries in implementing effective strategies to reduce iodine deficiency and its associated risks. Ultimately, this could lead to a sustainable decrease in the disease burden induced by iodine deficiency.

Eye Diseases "Treated" with Interoperable Medical Informatics

A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

During the screening period study eligibility will be assessed and the participants' individual LDL-C target according to guideline (Mach et al., 2020) will be determined. Among other criteria, at screening, a participant must be on a stable maximally tolerated dose of a HI statin with either atorvastatin ≥40 mg once a day (QD) or rosuvastatin ≥20 mg QD (+/- Ezetimibe [10mg]) for ≥ 4 weeks with which, however, a target LDL-C of < 70 mg/dL is not reached. During the open-label treatment period, all participants, who fulfill the inclusion/exclusion criteria, will be randomized at V1 (Day 1) in a 1:1 open-label fashion to either Inclisiran sodium 300 mg s.c. (administered at Day 1 and Day 90) or to BPA tablets 180 mg p.o. (given once daily). Participants will be required to maintain their background lipid-lowering treatment (maximally tolerated statin dose +/- Ezetimibe) unchanged for the duration of the study. The end of treatment (EOT) is reached at day 150. A Safety-Follow-up call will be conducted 30 days after EOT visit (Day 180). The overall study duration is approximately 190 days but can vary depending on individual screening and the visit windows allowed for the treatment period and EOS visit.

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML

A Study of Maribavir in Adults With Post-transplant Cytomegalovirus (CMV) Infection

This study will include two main periods of retrospective data collection from medical charts: the pre-index period and the post-index period. The index date is defined as the date of initiation of maribavir dosing, as documented in the medical records. The pre-index period covers the time from the transplant date to the index event, while the post-index period starts at the index event and ends at the date of chart abstraction, death, or loss to follow-up, whichever comes first.

Clinical Epidemiology in Contemporary Patients With Myelofibrosis.

Myeloproliferative neoplasms (MPNs) are rare bone marrow disorders characterized by clonal proliferation of hematopoietic cell lineages, and include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). MF has worse prognosis, with main causes of death including acute leukemia transformation, comorbid conditions, and consequences of cytopenia. MF is characterized by progressive anemia, bone marrow fibrosis, and extramedullary hematopoiesis with splenomegaly. Moreover, the disease is associated with a heavy symptom burden including night sweats, fever, bone pain, and weight loss and worsening the quality of life. On the beginning of 2013 the European Registry for Myeloproliferative Neoplasms (ERNEST) observational study was launched and approved by several IRBs of European hematological centers. The study focused on overt Primary (PMF) and Secondary myelofibrosis (SMF; i.e., post-Essential Thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia (post-PV MF)) and aimed at describing the clinical epidemiology of large series of patients observed in clinical practice. This research was justified as the landscape of both pathophysiological and clinical knowledge in MPNs was rapidly evolving, prompting to revise diagnostic criteria, prognostication and therapy recommendations. ERNEST retrospectively enrolled 1292 patients in whom the proposed prognostic models were confirmed to differentiate treatments in clinical practice, while ERNEST-2 reported results on critical events observed in 1010 of these cases during a median follow-up period of 5.4 years.4,5 The two studies closed in December 2022. In the last decade, new diagnostic and prognostic findings have been accumulated and the availability of new approved drugs, based on results of several new clinical trials, influenced the therapy decision making in the real-world clinical practice. Therefore, the continuation of observational studies in present ERNEST-3 on large multicenter case series of patients with MF is timely and might refine the results of clinical trials. The purpose of this study observational retrospective/prospective study is to gain information on MF associated cytopenias that represent a significant challenge in the contemporary patients with MF. Currently, there are few agents aimed at treating cytopenic MF, including immunomodulatory drugs, hypomethylating agents, and JAK inhibitors such as momelotinib and pacritinib, and development of new agents specifically tailored to this patient population remains an unmet need. Therefore, this study can provide data on these patients, focusing on clinical status, quality of life, comorbidities, and treatment results over time.

Initial Triple Therapy Including Parenteral Treprostinil vs Initial Double Oral Therapy in PAH Group I Patients

TripleTRE is prospective, randomized, two-arm, open-label, low-interventional, phase IV, multi-centre clinical trial comparing efficacy and safety of initial triple therapy including parenteral treprostinil to initial double oral therapy (standard of care (SoC)) by proportion of patients achieving low risk status according to the simplified four-strata risk-assessment tool from week 24 up to 48 weeks in 110 (55/group) treatment-naïve adult intermediate-high risk or intermediate-low risk participants with severe hemodynamic impairment with pulmonary arterial hypertension (PAH) (group I). Severe hemodynamic impairment is defined in current European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines as at least one of following conditions: mean right atrial pressure (RAP) ≥ 20 mmHg, cardiac index (CI) < 2.0 L/min, stroke volume index (SVI) < 31 mL/m2 and/or pulmonary vascular resistance (PVR) ≥ 12 WU. Risk status will be assessed with the simplified four-strata risk-assessment tool as per ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension (2022). TripleTRE will be performed in adult participants with a confirmed diagnosis of idiopathic PAH (IPAH), hereditary PAH (HPAH), drug and toxin-induced PAH (DPAH), PAH associated with Connective Tissue Disease (PAH-CTD) and PAH with corrected congenital heart disease (PAH-CHD). Participants will be randomized to one of the two treatment arms in 1:1 ratio. All patients will start with double oral background medication (endothelin receptor antagonist (ERA) and phosphodiesterase type-5 inhibitor (PDE-5i)). Choice of double oral drug combination underline the discretion of the investigator and applicable treatment guidelines. In both treatment arms all drugs (i.e., background medication in double oral group, background medication and parenteral treprostinil in initial triple group) will be initiated within 3 weeks after randomization. Patients randomized to treprostinil arm will receive training on infusion pump and medication after that investigational medicinal product will be handed out. All patients will be handed out diaries for documentation of treprostinil dose and used vials. Primary objective of TripleTRE is to investigate the effect of initial triple combination therapy compared to initial double oral therapy on risk status. The effect of initial triple combination therapy vs initial double oral therapy (SoC) will be measured by primary endpoint: (non)response to the assigned treatment, whereas therapy responders/non-responders are defined as: 1. Therapy-responder: achievement of low-risk status between week 24 and week 48 2. Therapy-non-responder: 1. pulmonary hypertension (PH) related deterioration to high-risk status, lung transplantation or death between week 12 and week 48 and/or 2. additional medication or change of initial PH specific medication due to unsatisfactory efficacy between week 12 and week 48 and/or 3. low risk status not achieved up to week 48 Risk status is assessed with the simplified four-strata risk-assessment tool as per ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension (2022). Commonly used variables such as hemodynamics, echocardiogram (ECHO) and time to clinical worsening will be evaluated as secondary endpoints. In addition, the emPHasis-10 questionnaire will be used as disease specific and validated patient-reported outcome tool for PAH patients. The European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) will be used as general patient-reported outcome tool independent from disease. TripleTRE trial is organized as a low-intervention trial consistent with definition in Clinical Trial Regulation (Regulation (EU) No 536/2014). Participants will not undergo any invasive examinations or laboratory evaluations, diagnostic or monitoring procedures specifically for the purposes of this trial that would expose them to increased risk compared to standard of care. Trial-related procedures as well as the frequency of assessments are in alignment with ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension (2022) and are not expected to pose additional risks to patients. Planned trial duration per patient is minimum 12 weeks and maximum 48 weeks with up to 10 visits depending on achievement of therapy responder (i.e., low risk status) or therapy non-responder status. The visits 2 and 3 can be performed on phone. Other visits will be performed on-site. The trial will only be conducted in countries where ERA and PDE-5i treatments are standard of care and treprostinil is available to patients. At the end of trial, patients will be treated according to routine medical care at the PH expert centers receiving locally reimbursed medications. Approximately 10 countries and 20 sites are planed. Statistical considerations: The complete statistical analysis plan (SAP) was finalized before first patient in (FPI) in meaning of first act of recruitment. A one-sided Boschloo exact test at 2.5% significance level will be used to test the following primary hypothesis: H0: Proportion of patients achieving low risk status (therapy responders) between week 24 and week 48 after baseline in the initial Triple treatment group is less or equal to the proportion of patients achieving low risk status between week 24 and week 48 after baseline in the initial Double oral treatment group. The null hypothesis will be rejected if the 97.5% CI of the difference of proportions of therapy responders (triple minus double) is greater than 0. To account for the variable time on treatment of therapy responders, a secondary sensitivity analysis will be performed by comparing the median time to the achievement of the low-risk status between the treatment groups. Further sensitivity and subgroup analyses are defined in detail the statistical analysis plan (SAP) including the handling of missing values.

Staphylococcus Aureus Bacteraemia (SAB)-Support-Study

Iberdomide Vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial for a maintenance therapy, for patients who underwent an induction therapy and autologous stem cell transplantation in the GMMG-HD8/DSMM XIX trial. Investigational Medicinal Product: Iberdomid (oral), isatuximab (subcutaneous administration via a wearable injector system). Randomisation will be performed centrally by GMMG/DSMM offices after verification of the eligibility of the patient. At the time of study inclusion, randomization will be performed into arm A (iberdomide) or arm B (iberdomide + isatuximab). Randomization will be stratified by centrally assessed MRD negativity status (yes vs. no vs. unknown); assessed by NGF from BMA; sensitivity of 10^-5; independent of standard IMWG response) and number of HDM/ASCT (single vs. tandem). Patients randomized in arm A will receive 39 cycles of the drug iberdomide, a Cereblon E3 Ubiquitin Ligase Modulating Drug (CELMoD®) that shares structural similarities to the immunomodulatory compounds (IMiDs) such as thalidomide and lenalidomide. Each cycle will last for 29 days. Patients in arm B will receive the same the 39 cycles of iberdomide plus monoclonal anti-CD38 antibody isatuximab subcutaneously. In both arms, patients will receive 20 mg dexamethasone in cycle 1, on the same days as the isatuximab administration in Arm B. End of study will be after 36 months of the maintenance therapy. There is one primary objective: - Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10^-6 via next-generation flow cytometry [NGF]) after two years of maintenance therapy. There is one key secondary objective: - PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first. Further secondary objectives are: - Rates of sustained MRD negativity (at sensitivity levels of 10-5 and 2x10^-6 via NGF from BMA) after 1, 2 and 3 years of maintenance therapy. - Conversion from MRD positive to negative (at sensitivity levels of 10^-5 and 2x10^-6 via NGF from BMA). - Rates of best overall response to treatment (BOR). - Rates of partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR). - Time-to-next-treatment (TTNT). - PFS on subsequent line of therapy. - Overall survival (OS). - Improvement of IMWG response categories (PR, VGPR, CR, sCR). - Proportions of patients in both treatment arms maintaining BOR and CR from baseline. - Assessment of quality-of-life (QoL) via the EORTC-QLQC30, EORTC-QLQMY20, and EQ-5D-5L questionnaires.

Early Genetic Identification of Obesity

TITLE: Whole genetic approach in Early Genetic Identification of Obesity (WEGIO) DESIGN: Multicenter epidemiological study STUDY POPULATION: Participants at risk for a syndromic or a monogenic genetic obesity, incl. participants clinically diagnosed with Bardet-Biedl-Syndrome (BBS) NUMBER OF PARTICIPANTS: 1000 for initial genetic sequencing and app. 40 for the follow-up documentation COORDINATING INVESTIGATOR: Prof. Dr. Arndt Rolfs PARTICIPATING COUNTRY: Germany TREATMENT: Not applicable PRIMARY OBJECTIVE: To investigate the prevalence of BBS in an at-risk population SECONDARY OBJECTIVES: - To explore genotype-phenotype correlation - To assess genotypes distribution in Germany and compare to other countries - To identify new genes/variants - To investigate clinical characteristics in individuals diagnosed with BBS DURATION OF RECRUITMENT: 32 months - total 24 months the recruitment of 1000 subjects 27 months follow up visits 32 months close out of sites INCLUSION CRITERIA: - Informed consent is obtained from the participant/parent/legal guardian - The participant is 2 years of age or older For a participant between 2 and 18 years of age: - The participant has and had a body weight more than 97th percentile before the age of 6 - The participant has one or more of the following symptoms: rod/cone dystrophy, renal abnormalities, ataxia, syndactyly, polydactyly, brachydactyly, hyperphagia, cognitive impairment, speech delay, hypogonadism For a participant who is 18 years of age or older: - The participant has BMI ≥ 30 kg/m2 - The participant had a body weight more than 97th percentile before the age of 6 years - The participant has rod/cone dystrophy - The participant is 2 or more years of age, is clinically diagnosed with Bardet-Biedl-Syndrome (BBS) or is a sibling of an individual diagnosed with BBS via the WEGIO study