Siegburg

The German-speaking Myeloma Multicenter Group (GMMG) registry is a national, observational, non-interventional, retro-and prospective clinical myeloma registry of multiple myeloma patients in Germany. The registry includes the study database of the prospective trials led by the GMMG, with basic data, diagnosis, therapy and longtime follow-up. The sample size is unlimited. The Myeloma Registry was activated on December 8, 2022. Currently 35 GMMG centers in Germany are participating. The first longtime follow-up data set included in the registry was the GMMG-HD 6 trial. The GMMG-HD6 trial is a phase 3 trial which investigated the efficacy of the addition of the anti-SLAMF7 monoclonal antibody, elotuzumab, to the standard induction and consolidation therapy consisting of lenalidomide, bortezomib and dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma. Target variables of interest are progression-free survival (PFS) from randomization, overall survival (OS), the follow-up time, the cause of death and the therapy free time after first relapse and its treatment. Further objectives will be defined and analyzed for each evaluation. Participations will be observed while the patient is being treated with standard of care until death, lost to follow-up or consent withdrawn. Follow-ups will be documented every six months until the 1st Progression Disease and then annually. The pseudonymized clinical data is stored in a separate database (eCRF) and is monitored centrally on a regular basis. The eCRF contain automated plausibility checks, so called queries.

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 (ASCT) in the GMMG-HD8/DSMM XIX trial or a similar quadruplet induction/consolidation therapy regimen followed by at least one ASCT. 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.

The objectives of this clinical study are to collect data on the safety of the Edwards PASCAL Transcatheter Valve Repair System and the Edwards PASCAL Precision Transcatheter Valve Repair System in transcatheter mitral valve repair and on the effectiveness of the Edwards PASCAL System and Edwards PASCAL Precision System in improving MR, functional status and quality of life in a post market setting.

RESOLVE is a pragmatic, cluster-randomised, open-label study designed to evaluate in real-world conditions the comparative effectiveness of two default dialysate sodium concentrations. Dialysis sites will be randomised in a 1:1 ratio to a default dialysate sodium concentration of 137mmol/l or 140mmol/l. 'Default' is defined as the use of the allocated dialysate sodium for ≥ 90% of delivered dialysis sessions in the unit. All other care will be according to standard local practices as determined by the site. Outcomes will be assessed on individual patients dialysing at those sites. Sites will be asked to consent to participation while waiver or opt-out consent will be sought for individual patients. It is anticipated that site accrual will occur over 5-7 years with average study duration expected to be approximately 2-5 years. The actual length of the study will be end-point determined.

Heart failure (HF), coronary artery disease (CAD) and atrial fibrillation (AF) are among the most relevant cardiovascular diseases contributing to overall morbidity and mortality each itself and in particular in case of their coexistence. Several new therapies have been introduced in randomized controlled trials but confirmation data of treatment effects in real-world cohorts using a standardized methodology is scarce. The International Consortium for Health Outcomes Measurement (ICHOM) defined standard variable sets for all three diseases in order to objectively monitor the course of disease. To evaluate current health care utilization and interactions between diseases and treatments in patients with HF, CAD and AF as well as patient-oriented values study initiator will build a prospective, observational, multicenter cardiovascular registry using standardized patient variables and endpoints based on the ICHOM recommendations.