Ludwigsburg

This study compares insulin icodec, taken once a week, with other basal insulins, taken once a day, in people with type 2 diabetes.The purpose of this study is to see how well the approved injectable weekly insulin icodec maintains blood sugar levels when compared to approved and available daily injectable basal insulins in people with type 2 diabetes. The participants will either be prescribed weekly insulin icodec or a daily basal insulin (insulin glargine, insulin detemir or insulin degludec) based on current standards for the treatment of type 2 diabetes. The study will last for about 13 months.

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 the study is to assess the efficacy and safety of the addition of Tersolisib (LY4064809/STX-478) to other anti-cancer drugs as first treatment for advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Participants can remain in the study as long as the drug is helping the cancer without unbearable side effects.

This study is open to adults with type 2 diabetes, high blood pressure, and cardiovascular disease. People can join the study if they have these conditions and do not have a history of heart failure. The purpose of this study is to find out if a medicine called vicadrostat, when taken with empagliflozin, helps reduce cardiovascular risk in people with these conditions. The study will compare this combination to a placebo version of vicadrostat with empagliflozin. Participants are put into 2 groups randomly, which means by chance. One group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets with empagliflozin. Placebo tablets look like vicadrostat tablets but do not contain any medicine. Participants take a tablet once per day for 2 and a half years and up to 4 years and 3 months. All participants also continue their medication for type 2 diabetes, high blood pressure, and cardiovascular disease. Participants have an equal chance of receiving the study medicine or placebo. Participants are in the study for up to 4 years and 3 months. During this time, they visit the study site regularly. During these visits, doctors collect information about participants' health and take blood samples. The doctors document when participants experience cardiovascular events. The doctors also regularly check participants' health and take note of any unwanted effects.

Eligible patients will be randomly allocated to both treatment arms in a 1:1 ratio. Within an accrual period of 4 years, 378 patients will be included per arm (756 in total) across all sites. The Follow-up period after surgery will take a minimum of 5 years. In the standard arm, radical hysterectomy is performed as per standard technique abdominal radical hysterectomy (Piver type 2 or 3 or Querleu \& Morrow Type B or C) with salpingectomy +/- oophorectomy. Ovaries may be removed or preserved +/- transposition. Surgery includes pelvic lymph node dissection or optional sentinel lymph node biopsy (SNB) according to current guidelines in both arms. In the experimental arm, radical hysterectomy is performed as per standard conventional 2D/3D laparoscopic or robotic assisted technique (Querleu \& Morrow Type B or C) with salpingectomy +/- oophorectomy. Ovaries may be removed or preserved +/- transposition. The following protective measures are mandatory for the minimally invasive arm: LEEP/conization prior to randomization or vaginal closure prior to colpotomy. Transcervical manipulators are not permitted. Use of uterus manipulators/ cervical adapter (without transcervical device) is allowed only after LEEP/conization. Meticulous dissection of pelvic (sentinel) lymph nodes including use of endobags and avoiding the dissemination of cancer cells will be implemented (tumor hygiene). Due to the positive results of the SHAPE trial published at Plante et al. NEJM 2024, in both arms simple hysterectomy can be considered for patients with low-risk early-stage cervical cancer (SHAPE criteria: tumor \< 2 cm, \< 10 mm depth of stromal invasion (LEEP/cone) BUT has to be determined BEFORE randomization. Simple hysterectomy has to be performed as extrafascial hysterectomy and the preparation of a max. 5 mm vaginal cuff is required to ensure negative margins. Surgery can be performed including removal of the sentinel lymph nodes following the concept of sentinel lymph node biopsy (SNB) and according to the current guidelines.

This is a multicenter, randomized, controlled, open-label study including patients with localized and locally advanced diffuse and mixed type adenocarcinoma of the stomach and Type II/III GEJ scheduled to receive perioperative chemotherapy combined with intraoperative HIPEC procedure. The scope of the trial is to evaluate the efficacy as well as the safety and tolerability of the combination of perioperative chemotherapy combined with an intraoperative HIPEC for resectable diffuse and mixed type gastric and GEJ (types II/III) adenocarcinoma. Intraoperative hyperthermic chemoperfusion is summarized under the abbreviation HIPEC in the following. Patients with localized and locally advanced diffuse or mixed type adenocarcinoma of the stomach and Type II/III GEJ (i.e. ≥cT3 any N or any T N-positive) with exclusion of distant metastases and after receiving neoadjuvant FLOT- therapy will be included in this trial after a central review. All enrolled patients will have received 3-6 pre-operative cycles (de-escalation or dose modification allowed) of biweekly FLOT (Docetaxel 50 mg/m² in 250 ml NaCl 0.9%, iv over 1 h; Oxaliplatin 85 mg/m² in 500 ml G5%, iv over 2h; Leucovorin 200 mg/m² in 250 ml NaCl 0.9%, iv over 30 min; 5-FU 2600 mg/m², iv over 24 h, q2wk) in the preoperative treatment phase. After completion of neoadjuvant FLOT- therapy followed by pre-operative tumor assessment, (also including diagnostic laparoscopy prior to start of FLOT), patients without disease progression (expected to be approximately 90% of the patients) will be included into the trial, stratified by initial clinical stage (N- vs. N+), histological type of tumor (Lauren classification diffuse vs. mixed) and study site. Patients will be randomized 1:1 to receive either postoperative FLOT (Arm A) or postoperative FLOT + intraoperative HIPEC (Arm B). Arm A (FLOT) Surgery in Arm A is planned to occur 4 to 6 weeks after d1 of last FLOT. Surgery is carried out in kind of gastrectomy, transhiatal extended gastrectomy. Following surgery, patients will receive four further 2-week treatment cycles FLOT in the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery. Arm B (FLOT/ HIPEC) Surgery in Arm B is planned to occur 4 to 6 weeks after d1 of last FLOT. Surgery is carried out in kind of gastrectomy, transhiatal extended gastrectomy. Surgery will be combined with an intraoperative Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) including cisplatin solution administered at a temperature of 42°C for 90 minutes. Following surgery, patients will receive four further 2-week treatment cycles FLOT in the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery. In both of the arms, tumor assessments (CT or MRI) are performed before randomization prior to surgery, and then every 3 months (radiological tumor assessment) thereafter until progression/relapse, death or end of follow-up. A change from CT into MRI in the follow up period is possible at any time. During treatment, clinical visits (blood cell counts, detection of toxicity) occur prior to every treatment dose. Safety of FLOT/ HIPEC will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported. The phase III design starts with a safety run-in phase. After 20 patients had curatively intended resection in Arm B, an interim safety analysis is performed that shows feasibility, safety, and tolerability of Arm B planned at the time 8 weeks after the 20th patient in Arm B had curatively intended resection. It is not planned to discontinue recruitment for the interim safety analysis.

Cirrhosis is a major cause of global health burden worldwide. Acute kidney injury (AKI) occurs in 20% of hospitalized patients with cirrhosis. Acute kidney injury is a relatively new definition of renal failure which takes into account the dynamic changes in serum creatinine. Among the causes of AKI, hepatorenal syndrome-AKI has the worst prognosis. HRS-AKI is an acute condition which occurs in patients with ascites, mainly refractory ascites. HRS-AKI includes the traditional hepatorenal syndrome type 1, which was defined by a serum creatinine cutoff and which has an ominous prognosis when left untreated, nevertheless HRS-AKI also includes milder forms of renal failure. The standard treatment of HRS-AKI is with the infusion of albumin and terlipressin. Although this treatment improves renal function, patients remain at risk for new episodes of HRS-AKI and liver transplantation should be considered. Nevertheless, this optimal solution is only a reality for a privileged few given the shortage of organs and the common presence of contraindications. Development of HRS-AKI is caused by increased pressure in the portal vein (the vein which brings the blood from the intestines to the liver), among other factors. Increased pressure in the portal vein, also called portal hypertension, is one of the main pathophysiological mechanisms that lead to the different complications of cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) is an interventional radiological procedure which reduces the pressure in the portal vein by creating a short-cut between the portal vein and the hepatic vein, the vein which brings the blood from the liver towards the heart. TIPS placement has become the mainstay of treatment of some complications of cirrhosis, namely variceal bleeding and refractory ascites. Although rationally plausible, the use of TIPS in HRS-AKI has not been evaluated in the context of randomized controlled trials. Indirect data suggest that it could be helpful, since patients who become TIPS have an improvement in renal hemodynamics and renal function as well as less episodes of HRS-AKI in the follow-up. On the other hand, traditional HRS type 1 can be associated to liver failure and cardiac alterations which contraindicate TIPS placement. HRS-AKI includes not only traditional HRS type 1, but also milder forms of the disease, so that it is reasonable to consider that TIPS placement may have a role in this condition. This study is a multicenter (14 centers), prospective, randomized controlled trial which evaluates use of TIPS in patients with HRS-AKI (stage 1, 2 and 3) versus standard of care (albumin and terlipressin). Patients with cirrhosis and HRS-AKI who fulfill the inclusion criteria and do not have any exclusion criteria will be randomized to standard of care or standard of care and TIPS. Patients will be followed for a minimum of 12 months until the end of the trial. The main end-point is to compare the survival at the end of follow-up among the two groups.

Eligible patients will be those patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III/IV, except FIGO stage IIIA2 without nodal involvement) invasive high grade non-mucinous, non-clear cell epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer, who have either undergone upfront primary surgery or plan to undergo chemotherapy with interval debulking surgery (IDS). In addition, patients should not have any medical contraindications that would exclude treatment with bevacizumab and/or niraparib. All eligible patients will receive the first cycle of chemotherapy (carboplatin area under curve \[AUC\] 5 and paclitaxel 175 mg/m²) as part of Study Run-In-Period (cycle 1). In parallel, central laboratory will determine the breast cancer (BRCA) status in tumor tissue (tBRCA). All patients with a valid central tBRCA test result will be randomized within 3 days prior to day 1 of cycle 2 in a 1:1 ratio in the following treatment arms: Arm 1: Patients will receive further 5 cycles of carboplatin and paclitaxel q21d followed by niraparib once daily for up to a total of 3 years Arm 2: Patients will receive further 5 cycles of carboplatin and paclitaxel plus bevacizumab q21d followed by bevacizumab q21d (for up to 1 year) and niraparib once daily for up to a total of 3 years. The study aims to investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / niraparib is superior to the treatment of carboplatin / paclitaxel / niraparib-Inhibitor in an all-comer population.

This is a prospective, randomized, double-blinded, placebo-controlled, multi-center, Phase 3 study of GLSI-100 immunotherapy in HLA-A\*02 positive and HER2/neu positive subjects who are at high risk for disease recurrence and have completed both neoadjuvant and postoperative adjuvant standard of care therapy. Treatment consists of 6 intradermal injections, Primary Immunization Series (PIS), over the first 6 months of treatment and 5 booster intradermal injections spaced 6 months apart. A third open-label arm will explore GLSI-100 immunotherapy in non-HLA-A\*02 positive and HER2/neu positive subjects.

This is a Phase III, randomized, open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig monotherapy versus Pembrolizumab monotherapy for the first-line treatment of participants with locally-advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.